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Upon
successful completion of this course, you will be able to:
- Identify
and discuss the five major strategies for the prevention
and control of STDs
- Explain
what is meant by special populations and explain
the special prevention-control issues they face
- Identify
and explain the key elements of HIV Infection: Detection,
Counseling, and Referral
- List
and discuss the major STDs that health care professionals
have to deal with today
These
guidelines for the treatment of persons who have sexually
transmitted diseases (STDs) were developed by CDC after consultation
with a group of professionals knowledgeable in the field of
STDs who met in Atlanta, Georgia, during April 19--21, 2005.
The information in this report updates the Sexually Transmitted
Diseases Treatment Guidelines, 2002 (MMWR 2002;51[No. RR-6]).
Included in these updated guidelines are an expanded diagnostic
evaluation for cervicitis and trichomoniasis; new antimicrobial
recommendations for trichomoniasis; additional data on the
clinical efficacy of azithromycin for chlamydial infections
in pregnancy; discussion of the role of Mycoplasma genitalium
and trichomoniasis in urethritis/cervicitis and treatment-related
implications; emergence of lymphogranuloma venereum protocolitis
among men who have sex with men (MSM); expanded discussion
of the criteria for spinal fluid examination to evaluate for
neurosyphilis; the emergence of azithromycin- resistant Treponema
pallidum; increasing prevalence of quinolone-resistant Neisseria
gonorrhoeae in MSM; revised discussion concerning the sexual
transmission of hepatitis C; postexposure prophylaxis after
sexual assault; and an expanded discussion of STD prevention
approaches. The material in this report originated in National
Center for HIV, Viral Hepatitis, STDs, and Tuberculosis Prevention
(proposed), Kevin A. Fenton, MD, PhD, Director; and the Division
of STD Prevention, John M. Douglas, MD, Director.
Physicians
and other health-care providers play a critical role in preventing
and treating sexually transmitted diseases (STDs). These guidelines
for the treatment of STDs are intended to assist with that
effort. Although these guidelines emphasize treatment, prevention
strategies and diagnostic recommendations also are discussed.
Methods
This
report was produced through a multistage process. Beginning
in 2004, CDC personnel and professionals knowledgeable in
the field of STDs systematically reviewed evidence, including
published abstracts and peer-reviewed journal articles concerning
each of the major STDs, focusing on information that had become
available since publication of the Sexually Transmitted Diseases
Treatment Guidelines, 2002. Background papers were written
and tables of evidence were constructed summarizing the type
of study (e.g., randomized controlled trial or case series),
study population and setting, treatments or other interventions,
outcome measures assessed, reported findings, and weaknesses
and biases in study design and analysis. A draft document
was developed on the basis of the reviews.
In
April 2005, CDC staff members and invited consultants assembled
in Atlanta, Georgia, for a 3-day meeting to present the key
questions regarding STD treatment that emerged from the evidence-based
reviews and the information available to answer those questions.
When relevant, the questions focused on four principal outcomes
of STD therapy for each individual disease:
1) microbiologic cure,
2) alleviation of signs and symptoms,
3) prevention of sequelae, and
4) prevention of transmission.
Cost-effectiveness
and other advantages (e.g., single-dose formulations and directly
observed therapy of specific regimens) also were discussed.
The consultants then assessed whether the questions identified
were relevant, ranked them in order of priority, and attempted
to arrive at answers using the available evidence. In addition,
the consultants evaluated the quality of evidence supporting
the answers on the basis of the number, type, and quality
of the studies.
In
several areas, the process diverged from that previously described.
The sections on hepatitis B virus (HBV) and hepatitis A virus
(HAV) infections are based on previously or recently approved
recommendations of the Advisory Committee on Immunization
Practices. The recommendations for STD screening during pregnancy
were developed after CDC staff reviewed the recommendations
from other knowledgeable groups.
Throughout
this report, the evidence used as the basis for specific recommendations
is discussed briefly. More comprehensive, annotated discussions
of such evidence will appear in background papers that will
be published in a supplement issue of Clinical Infectious
Diseases. When more than one therapeutic regimen is recommended,
the sequence is in alphabetical order unless the choices for
therapy are prioritized based on efficacy, convenience, or
cost. For STDs with more than one recommended treatment regimen,
it can be assumed that all regimens have similar efficacy
and similar rates of intolerance or toxicity, unless otherwise
specified. Persons treating STDs should use recommended regimens
primarily; alternative regimens can be considered in instances
of substantial drug allergy or other contraindications to
the recommended regimens.
These recommendations were developed in consultation with
public and private sector professionals knowledgeable in the
treatment of persons with STDs. The recommendations are applicable
to various patient-care settings, including family planning
clinics, private physicians' offices, managed care organizations,
and other primary-care facilities.
These
recommendations are meant to serve as a source of clinical
guidance: health-care providers should always consider the
individual clinical circumstances of each person in the context
of local disease prevalence. These guidelines focus on the
treatment and counseling of individual persons and do not
address other community services and interventions that are
important in STD/human immunodeficiency virus (HIV) prevention.
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Clinical
Prevention Guidance
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The
prevention and control of STDs are based on the following
five major strategies:
1) education and counseling of persons at risk on ways to
avoid STDs through changes in sexual behaviors;
2) identification of asymptomatically infected persons and
of symptomatic persons unlikely to seek diagnostic and treatment
services;
3) effective diagnosis and treatment of infected persons;
4) evaluation, treatment, and counseling of sex partners of
persons who are infected with an STD; and
5) preexposure vaccination of persons at risk for vaccine-preventable
STD.
Primary
prevention of STD begins with changing the sexual behaviors
that place persons at risk for infection. Health-care providers
have a unique opportunity to provide education and counseling
to their patients. As part of the clinical interview, health-care
providers should routinely and regularly obtain sexual histories
from their patients and address management of risk reduction
as indicated in this report. Guidance in obtaining a sexual
history is available in Contraceptive Technology, 18th edition
(5) and in the curriculum provided by CDC's STD/HIV Prevention
Training Centers (http://www.stdhivpreventiontraining.org).
Counseling
skills, characterized by respect, compassion, and a nonjudgmental
attitude toward all patients, are essential to obtaining a
thorough sexual history and to delivering prevention messages
effectively. Key techniques that can be effective in facilitating
rapport with patients include the use of 1) open-ended questions
(e.g., "Tell me about any new sex partners you've had
since your last visit" and "what's your experience
with using condoms been like?"), 2) understandable language
("have you ever had a sore or scab on your penis?"),
and 3) normalizing language ("some of my patients have
difficulty using a condom with every sex act. How is it for
you?"). One approach to eliciting information concerning
five key areas of interest has been summarized.
The
Five Ps: Partners, Prevention of Pregnancy, Protection from
STDs, Practices, Past History of STDs
1.
Partners
- "Do
you have sex with men, women, or both?"
- "In
the past 2 months, how many partners have you had sex with?"
- "In
the past 12 months, how many partners have you had sex with?"
2.
Prevention of pregnancy
- "Are
you or your partner trying to get pregnant?" If no,
"What are you doing to prevent pregnancy?"
3.
Protection from STDs
1.
"What do you do to protect yourself from STDs and HIV?"
4.
Practices
- "To
understand your risks for STDs, I need to understand the
kind of sex you have had recently."
- "Have
you had vaginal sex, meaning `penis in vagina sex'"?
- If
yes, "Do you use condoms: never, sometimes, or always?"
- "Have
you had anal sex, meaning `penis in rectum/anus sex'"?
- If
yes, "Do you use condoms: never, sometimes, or always?"
- "Have
you had oral sex, meaning `mouth on penis/vagina'"?
For
condom answers
- If
"never:" "Why don't you use condoms?"
-
If "sometimes": "In what situations or with
whom, do you not use condoms?"
5.
Past history of STDs
- "Have
you ever had an STD?"
- "Have
any of your partners had an STD?"
Additional
questions to identify HIV and hepatitis risk
- "Have
you or any of your partners ever injected drugs?
- "Have
any of your partners exchanged money or drugs for sex?"
- "Is
there anything else about your sexual practices that I need
to know about?"
Patients
should be reassured that treatment will be provided regardless
of individual circumstances (e.g., ability to pay, citizenship
or immigration status, language spoken, or specific sex practices).
Many patients seeking treatment or screening for a particular
STD should be evaluated for all common STDs; even so, all
patients should be informed concerning all the STDs for which
they are being tested and if testing for a common STD (e.g.,
genital herpes) is not being performed.
STD/HIV
Prevention Counseling
Effective
delivery of prevention messages requires that providers integrate
communication of general risk reduction messages that are
relevant to the client (i.e., client-centered counseling)
and education regarding specific actions that can reduce the
risk for STD/HIV transmission (e.g., abstinence, condom use,
limiting the number of sex partners, modifying sexual behaviors,
and vaccination). Each of these specific actions is discussed
separately in this report.
- Interactive
counseling approaches directed at a patient's personal risk,
the situations in which risk occurs, and the use of goal-setting
strategies are effective in STD/HIV prevention. One such
approach, client-centered STD/HIV prevention counseling,
involves tailoring a discussion of risk reduction to the
patient's individual situation. Client-centered counseling
can have a beneficial effect on the likelihood of patients
using risk-reduction practices and can reduce the risk for
future acquisition of an STD. One effective client-centered
approach is Project RESPECT, which demonstrated that a brief
counseling intervention was associated with a reduced frequency
of STD/HIV risk-related behaviors and with a lowered acquisition
of STDs. Practice models based on Project RESPECT have been
successfully implemented in clinic-based settings. Other
approaches use motivational interviewing to move clients
toward achievable risk reduction goals. CDC provides additional
information on these and other effective behavioral interventions
at http://effectiveinterventions.org.
- Interactive
counseling can be used effectively by all health-care providers
or can be conducted by specially trained counselors. The
quality of counseling is best ensured when providers receive
basic training in prevention counseling methods and skill-building
approaches, periodic observation of counseling with immediate
feedback by persons with expertise in the counseling approach,
periodic counselor and/or patient satisfaction evaluations,
and availability of expert assistance or referral for challenging
situations. Training in client-centered counseling is available
through the CDC STD/HIV Prevention Training Centers (http://www.stdhivpreventiontraining.org).
Prevention counseling is most effective if provided in a
nonjudgmental manner appropriate to the patient's culture,
language, sex, sexual orientation, age, and developmental
level.
In
addition to individual prevention counseling, some videos
and large group presentations provide explicit information
concerning how to use condoms correctly. These have been effective
in reducing the occurrence of additional STDs among persons
at high risk, including STD clinic patients and adolescents.
Because
the incidence of some STDs, notably syphilis, has increased
in HIV-infected persons, the use of client-centered STD counseling
for HIV-infected persons has received strong emphasis from
public health agencies and organizations. Consensus guidelines
issued by CDC, the Health Resources and Services Administration,
the HIV Medicine Association of the Infectious Diseases Society
of America, and the National Institutes of Health emphasize
that STD/HIV risk assessment, STD screening, and client-centered
risk reduction counseling should be provided routinely to
HIV-infected persons. Several specific methods have been designed
for the HIV care setting. Additional information regarding
these approaches is available at http://effectiveinterventions.org.
Prevention
Methods
Client-Initiated
Interventions to Reduce Sexual Transmission of STD/HIV and
Unintended Pregnancy
Abstinence
and Reduction of Number of Sex Partners
The
most reliable way to avoid transmission of STDs is to abstain
from sex (i.e., oral, vaginal, or anal sex) or to be in a
long-term, mutually monogamous relationship with an uninfected
partner. Counseling that encourages abstinence from sexual
intercourse is crucial for persons who are being treated for
an STD (or whose partners are undergoing treatment) and for
persons who want to avoid the possible consequences of sex
completely (e.g., STD/HIV and unintended pregnancy). A more
comprehensive discussion of abstinence is available in Contraceptive
Technology, 18th edition. For persons embarking on a mutually
monogamous relationship, screening for common STDs before
initiating sex might reduce the risk for future transmission
of asymptomatic STDs.
Preexposure
Vaccination
Preexposure
vaccination is one of the most effective methods for preventing
transmission of some STDs. For example, because HBV infection
is frequently sexually transmitted, hepatitis B vaccination
is recommended for all unvaccinated, uninfected persons being
evaluated for an STD. In addition, hepatitis A vaccine is
licensed and is recommended for men who have sex with men
(MSM) and illicit drug users (i.e., both injecting and noninjecting).
Specific details regarding hepatitis A and B vaccination are
available at http://cdc.gov/hepatitis.
A quadrivalent vaccine against human papillomavirus (HPV types
6, 11, 16, 18) is now available and licensed for females aged
9--26 years. Vaccine trials for other STDs are being conducted.
Male
Condoms
When
used consistently and correctly, male latex condoms are highly
effective in preventing the sexual transmission of HIV infection
(i.e., HIV-negative partners in heterosexual serodiscordant
relationships in which condoms were consistently used were
80% less likely to become HIV-infected compared with persons
in similar relationships in which condoms were not used) and
can reduce the risk for other STDs, including chlamydia, gonorrhea,
and trichomoniasis, and might reduce the risk of women developing
pelvic inflammatory disease (PID). Condom use might reduce
the risk for transmission of herpes simplex virus-2 (HSV-2),
although data for this effect are more limited. Condom use
might reduce the risk for HPV-associated diseases (e.g., genital
warts and cervical cancer) and mitigate the adverse consequences
of infection with HPV, as their use has been associated with
higher rates of regression of cervical intraepithelial neoplasia
(CIN) and clearance of HPV infection in women, and with regression
of HPV-associated penile lesions in men. A limited number
of prospective studies have demonstrated a protective effect
of condoms on the acquisition of genital HPV; one recent prospective
study among newly sexually active college women demonstrated
that consistent condom use was associated with a 70% reduction
in risk for HPV transmission.
Condoms
are regulated as medical devices and are subject to random
sampling and testing by the Food and Drug Administration (FDA).
Each latex condom manufactured in the United States is tested
electronically for holes before packaging. Rates of condom
breakage during sexual intercourse and withdrawal are approximately
two broken condoms per 100 condoms used in the United States.
The failure of condoms to protect against STD transmission
or unintended pregnancy usually results from inconsistent
or incorrect use rather than condom breakage.
Male
condoms made of materials other than latex are available in
the United States. Although they have had higher breakage
and slippage rates when compared with latex condoms and are
usually more costly, the pregnancy rates among women whose
partners use these condoms are similar to latex condoms. Two
general categories of nonlatex condoms exist. The first type
is made of polyurethane or other synthetic material and provides
protection against STD/HIV and pregnancy equal to that of
latex condoms. These can be substituted for persons with latex
allergy. The second type is natural membrane condoms (frequently
called "natural" condoms or, incorrectly, lambskin
condoms). These condoms are usually made from lamb cecum and
can have pores up to 1500 nm in diameter. Whereas these pores
do not allow the passage of sperm, they are more than 10 times
the diameter of HIV and more than 25 times that of HBV. Moreover,
laboratory studies demonstrate that viral STD transmission
can occur with natural membrane condoms. Using natural membrane
condoms for protection against STDs is not recommended.
Patients
should be advised that condoms must be used consistently and
correctly to be effective in preventing STDs, and they should
be instructed in the correct use of condoms. The following
recommendations ensure the proper use of male condoms:
- Use
a new condom with each sex act (e.g., oral, vaginal, and
anal).
- Carefully
handle the condom to avoid damaging it with fingernails,
teeth, or other sharp objects.
- Put
the condom on after the penis is erect and before any genital,
oral, or anal contact with the partner.
- Use
only water-based lubricants (e.g., K-Y Jelly, Astroglide,
AquaLube, and glycerin) with latex condoms. Oil-based
lubricants (e.g., petroleum jelly, shortening, mineral oil,
massage oils, body lotions, and cooking oil) can weaken
latex.
- Ensure
adequate lubrication during vaginal and anal sex, which
might require the use of exogenous water-based lubricants.
- To
prevent the condom from slipping off, hold the condom firmly
against the base of the penis during withdrawal, and withdraw
while the penis is still erect.
Female
Condoms
Laboratory
studies indicate that the female condom (Reality), which
consists of a lubricated polyurethane sheath with a ring on
each end that is inserted into the vagina, is an effective
mechanical barrier to viruses, including HIV, and to semen.
A limited number of clinical studies have evaluated the efficacy
of female condoms in providing protection from STDs, including
HI. If used consistently and correctly, the female condom
might substantially reduce the risk for STDs. When a male
condom cannot be used properly, sex partners should consider
using a female condom. Female condoms are costly compared
with male condoms. The female condom also has been used for
STD/HIV protection during receptive anal intercourse. Whereas
it might provide some protection in this setting, its efficacy
is undefined.
Vaginal
Spermicides and Diaphragms
Vaginal
spermicides containing nonoxynol-9 (N-9) are not effective
in preventing cervical gonorrhea, chlamydia, or HIV infection.
Furthermore, frequent use of spermicides containing N-9 has
been associated with disruption of the genital epithelium,
which might be associated with an increased risk for HIV transmission.
Therefore, N-9 is not recommended for STD/HIV prevention.
In case-control and cross-sectional studies, diaphragm use
has been demonstrated to protect against cervical gonorrhea,
chlamydia, and trichomoniasis; a randomized controlled trial
will be conducted. On the basis of all available evidence,
diaphragms should not be relied on as the sole source of protection
against HIV infection. Diaphragm and spermicide use have been
associated with an increased risk for bacterial urinary tract
infections in women.
Condoms
and N-9 Vaginal Spermicides
Condoms
lubricated with spermicides are no more effective than other
lubricated condoms in protecting against the transmission
of HIV and other STDs, and those that are lubricated with
N-9 pose the concerns that have been previously discussed.
Use of condoms lubricated with N-9 is not recommended for
STD/HIV prevention because spermicide-coated condoms cost
more, have a shorter shelf-life than other lubricated condoms,
and have been associated with urinary tract infection in young
women.
Rectal
Use of N-9 Spermicides
Recent
studies indicate that N-9 might increase the risk for HIV
transmission during vaginal intercourse. Although similar
studies have not been conducted among men who use N-9 spermicide
during anal intercourse with other men, N-9 can damage the
cells lining the rectum, which might provide a portal of entry
for HIV and other sexually transmissible agents. Therefore,
N-9 should not be used as a microbicide or lubricant during
anal intercourse.
Nonbarrier
Contraception, Surgical Sterilization, and Hysterectomy
Sexually
active women who are not at risk for pregnancy might incorrectly
perceive themselves to be at no risk for STDs, including HIV
infection. Contraceptive methods that are not mechanical barriers
offer no protection against HIV or other STDs. Women who use
hormonal contraception (e.g., oral contraceptives, Norplant,
and Depo-Provera), have intrauterine devices (IUD),
have been surgically sterilized, or have had hysterectomies
should be counseled regarding the use of condoms and the risk
for STDs, including HIV infection.
Emergency
Contraception (EC)
Emergency
use of oral contraceptive pills containing levonorgesterol
alone reduces the risk for pregnancy after unprotected intercourse
by 89%. Pills containing a combination of ethinyl estradiol
and either norgestrel or levonorgestrel can be used and reduce
the risk for pregnancy by 75%. Emergency insertion of a copper
IUD also is highly effective, reducing the risk by as much
as 99%. EC with oral contraceptive pills should be initiated
as soon as possible after unprotected intercourse and definitely
within 120 hours (i.e., 5 days). The only medical contraindication
to provision of EC is current pregnancy.
Providers
who manage persons at risk for STDs should counsel women concerning
the option for EC, if indicated, and provide it in a timely
fashion if desired by the woman. Plan B (two 750 mcg levonorgestrel
tablets) has been approved by FDA and is available in the
United States for the prevention of unintended pregnancy.
Additional information on EC is available in Contraceptive
Technology, 18th edition, or at http://www.arhp.org/healthcareproviders/resources/contraceptionresources.
Postexposure
Prophylaxis (PEP) for HIV
Guidelines
for the use of PEP aimed at preventing HIV acquisition as
a result of sexual exposure are available and are discussed
in this report (see Sexual Assault and STDs).
Partner
Management
Partner
notification, previously referred to as "contact tracing"
but recently included in the broader category of partner services,
is the process by which providers or public health authorities
learn from persons with STDs about their sex partners and
help to arrange for the evaluation and treatment of sex partners.
Providers can seek this information and help to arrange for
evaluation and treatment of sex partners, either directly
or with assistance from state and local health departments.
The intensity of partner services and the specific STDs for
which they are offered vary among providers, agencies, and
geographic areas. Ideally, such services should be accompanied
by health counseling and might include referral of patients
and their partners for other services, whenever appropriate.
In
general, whether partner notification effectively decreases
exposure to STDs and whether it changes the incidence and
prevalence of STDs in a community are uncertain. The paucity
of supporting evidence regarding the effectiveness of partner
notification has spurred the exploration of alternative approaches.
One such approach is to place partner notification in a larger
context by making interventions in the sexual and social networks
in which persons are exposed to STDs. Prospective evaluations
incorporating assessment of venues, community structure, and
social and sexual, contacts in conjunction with partner notification
of efforts are promising in terms of increasing case-finding
and warrant further exploration. The scope of such efforts
probably precludes individual clinician efforts to use network-based
approaches, but STD-control programs might find them useful.
Many
persons individually benefit from partner notification. When
partners are treated, index patients have reduced risk for
reinfection. At a population level, partner notification can
disrupt networks of STD transmission and reduce disease incidence.
Therefore, providers should encourage their patients with
STDs to notify their sex partners and urge them to seek medical
evaluation and treatment, regardless of whether assistance
is available from health agencies. When medical evaluation,
counseling, and treatment of partners cannot be done because
of the particular circumstances of a patient or partner or
because of resource limitations, other partner management
options can be considered. One option is patient-delivered
therapy, a form of expedited partner therapy (EPT) in which
partners of infected patients are treated without previous
medical evaluation or prevention counseling (http://www.cdc.gov/std/treatment/EPTFinalReport2006.pdf).
The
evidence supporting patient-delivered therapy is based on
three clinical trials that included heterosexual men and women
with chlamydia or gonorrhea. The strength of the supporting
evidence differed by STD and by the sex of the index case
when reinfection of the index case was the measured outcome.
Despite this variation, patient-delivered therapy (i.e., via
medications or prescriptions) can prevent reinfection of index
case and has been associated with a higher likelihood of partner
notification, compared with unassisted patient referral of
partners. Medications and prescriptions for patient-delivered
therapy should be accompanied by treatment instructions, appropriate
warnings about taking medications if pregnant, general health
counseling, and advice that partners should seek personal
medical evaluations, particularly women with symptoms of STDs
or PID. Existing data suggest that EPT has a limited role
in partner management for trichomoniasis. No data support
its use in the routine management of syphilis. There is no
experience with expedited partner therapy for gonorrhea or
chlamydia infection among MSM. Currently, EPT is not feasible
in many settings because of operational barriers, including
the lack of clear legal status of EPT in some states.
Reporting
and Confidentiality
The
accurate and timely reporting of STDs is integrally important
for assessing morbidity trends, targeting limited resources,
and assisting local health authorities in partner notification
and treatment. STD/HIV and acquired immunodeficiency syndrome
(AIDS) cases should be reported in accordance with state and
local statutory requirements. Syphilis, gonorrhea, chlamydia,
chanroid, HIV infection, and AIDS are reportable diseases
in every state. The requirements for reporting other STDs
differ by state, and clinicians should be familiar with state
and local reporting requirements.
Reporting can be provider- and/or laboratory-based. Clinicians
who are unsure of state and local reporting requirements should
seek advice from state or local health departments or STD
programs. STD and HIV reports are kept strictly confidential.
In the majority of jurisdictions, such reports are protected
by statute from subpoena. Before public health representatives
conduct a follow-up of a positive STD-test result, they should
consult the patient's health-care provider to verify the diagnosis
and treatment.
Pregnant
Women
Intrauterine
or perinatally transmitted STDs can have severely debilitating
effects on pregnant women, their partners, and their fetuses.
All pregnant women and their sex partners should be asked
about STDs, counseled about the possibility of perinatal infections,
and ensured access to treatment, if needed.
Recommended
Screening Tests
- All
pregnant women in the United States should be tested for
HIV infection as early in pregnancy as possible. Testing
should be conducted after the woman is notified that she
will be tested for HIV as part of the routine panel of prenatal
tests, unless she declines the test (i.e., opt-out screening).
For women who decline HIV testing, providers should address
their objections, and where appropriate, continue to strongly
encourage testing. Women who decline testing because they
have had a previous negative HIV test should be informed
of the importance of retesting during each pregnancy. Testing
pregnant women is vital not only to maintain the health
of the patient but also because interventions (i.e., antiretroviral
and obstetrical) are available that can reduce perinatal
transmission of HIV. Retesting in the third trimester (i.e.,
preferably before 36 weeks' gestation) is recommended for
women at high risk for acquiring HIV infection (i.e., women
who use illicit drugs, have STDs during pregnancy, have
multiple sex partners during pregnancy, or have HIV-infected
partners). Rapid HIV testing should be performed on women
in labor with undocumented HIV status. If a rapid HIV test
result is positive, antiretroviral prophylaxis (with consent)
should be administered without waiting for the results of
the confirmatory test.
- A
serologic test for syphilis should be performed on all pregnant
women at the first prenatal visit. In populations in which
use of prenatal care is not optimal, rapid plasma reagin
(RPR) card test screening (and treatment, if that test is
reactive) should be performed at the time a pregnancy is
confirmed. Women who are at high risk for syphilis, live
in areas of high syphilis morbidity, are previously untested,
or have positive serology in the first trimester should
be screened again early in the third trimester (28 weeks'
gestation) and at delivery. Some states require all women
to be screened at delivery. Infants should not be discharged
from the hospital unless the syphilis serologic status of
the mother has been determined at least one time during
pregnancy and preferably again at delivery. Any woman who
delivers a stillborn infant should be tested for syphilis.
- All
pregnant women should be routinely tested for hepatitis
B surface antigen (HBsAg) during an early prenatal visit
(e.g., first trimester) in each pregnancy, even if they
have been previously vaccinated or tested. Women who were
not screened prenatally, those who engage in behaviors that
put them at high risk for infection (e.g., more than one
sex partner in the previous 6 months, evaluation or treatment
for an STD, recent or current injecting-drug use, and HBsAg-positive
sex partner), and those with clinical hepatitis should be
retested at the time of admission to the hospital for delivery.
Women at risk for HBV infection also should be vaccinated.
To avoid misinterpreting a transient positive HBsAg result
during the 21 days after vaccination, HBsAg testing should
be performed before the vaccination.
- All
laboratories that conduct HBsAg tests should use an HBsAg
test that is FDA-cleared and should perform testing according
to the manufacturer's labeling, including testing of initially
reactive specimens with a licensed neutralizing confirmatory
test. When pregnant women are tested for HBsAg at the time
of admission for delivery, shortened testing protocols may
be used, and initially reactive results should prompt expedited
administration of immunoprophylaxis to infants.
- All
pregnant women should be routinely tested for Chlamydia
trachomatis (see Chlamydia Infections, Diagnostic Considerations)
at the first prenatal visit. Women aged <25 years and
those at increased risk for chlamydia (i.e., women who have
a new or more than one sex partner) also should be retested
during the third trimester to prevent maternal postnatal
complications and chlamydial infection in the infant. Screening
during the first trimester might prevent the adverse effects
of chlamydia during pregnancy, but supportive evidence for
this is lacking. If screening is performed only during the
first trimester, a longer period exists for acquiring infection
before delivery.
- All
pregnant women at risk for gonorrhea or living in an area
in which the prevalence of Neisseria gonorrhoeae is high
should be tested at the first prenatal visit for N. gonorrhoeae.
(See Gonococcal Infections, Diagnostic Considerations).
A repeat test should be performed during the third trimester
for those at continued risk.
- All
pregnant women at high risk for hepatitis C infection should
be tested for hepatitis C antibodies (see Hepatitis C, Diagnostic
Considerations) at the first prenatal visit. Women at high
risk include those with a history of injecting-drug use
and those with a history of blood transfusion or organ transplantion
before 1992.
- Evaluation
for bacterial vaginosis (BV) might be conducted during the
first prenatal visit for asymptomatic patients who are at
high risk for preterm labor (e.g., those who have a history
of a previous preterm delivery). Evidence does not support
routine testing for BV.
- A
Papanicolaou (Pap) smear should be obtained at the first
prenatal visit if none has been documented during the preceding
year.
Other
Concerns
-
Women who are HBsAg positive should be reported to the local
and/or state health department to ensure that they are entered
into a case-management system and that timely and appropriate
prophylaxis is provided for their infants. Information concerning
the pregnant woman's HBsAg status should be provided to
the hospital in which delivery is planned and to the health-care
provider who will care for the newborn. In addition, household
and sex contacts of women who are HBsAg positive should
be vaccinated.
- Women
who are HBsAg positive should be provided with, or referred
for, appropriate counseling and medical management. Pregnant
women who are HBsAg positive pregnant women should receive
information regarding hepatitis B that addresses
--- modes of transmission;
--- perinatal concerns (e.g., breastfeeding is not contraindicated);
--- prevention of HBV transmission, including the importance
of postexposure prophylaxis for the newborn infant and hepatitis
B vaccination for household contacts and sex partners; and
--- evaluation for and treatment of chronic HBV infection.
- No
treatment is available for HCV-infected pregnant women.
However, all women with HCV infection should receive appropriate
counseling and supportive care as needed (see Hepatitis
C, Prevention). No vaccine is available to prevent HCV transmission.
- In
the absence of lesions during the third trimester, routine
serial cultures for HSV are not indicated for women who
have a history of recurrent genital herpes. Prophylactic
cesarean section is not indicated for women who do not have
active genital lesions at the time of delivery. In addition,
insufficient evidence exists to recommend routine HSV-2
serologic screening among previously undiagnosed women during
pregnancy, nor does sufficient evidence exist to recommend
routine antiviral suppressive therapy late in gestation
for all HSV-2 positive women.
- The
presence of genital warts is not an indication for cesarean
section.
- Not
enough evidence exists to recommend routine screening for
Trichomonas vaginalis in asymptomatic pregnant women.
For
a more detailed discussion of STD testing and treatment among
pregnant women and other infections not transmitted sexually,
refer to the following references: Guide to Clinical Preventive
Services; Guidelines for Perinatal Care; ACOG Practice Bulletin:
Prophylatic Antibiotics in Labor and Delivery; ACOG Committee
Opinion: Primary and Preventive Care: Periodic Assessments;
Recommendations for the Prevention and Management of Chlamydia
trachomatis Infections; Hepatitis B Virus: A Comprehensive
Strategy for Eliminating Transmission in the United States---Recommendations
of the Immunization Practices Advisory Committee (ACIP); Mother-To-Infant
Transmission of Hepatitis C Virus; Hepatitis C: Screening
in Pregnancy; American College of Obstetricians and Gynecologists
(ACOG) Educational Bulletin: Viral Hepatitis in Pregnancy;
Revised Public Health Service Recommendations for HIV Screening
of Pregnant Women; Prenatal and Perinatal Human Immunodeficiency
Virus Testing: Expanded Recommendations; US Preventative Task
Force HIV Screening Guidelines; Rapid HIV Antibody Testing
During Labor and Delivery for Women of Unknown HIV Status:
A Practical Guide and Model Protocol; and Sexually Transmitted
Diseases in Adolescents.
These
sources are not entirely consistent in their recommendations.
For example, the Guide to Clinical Preventive Services recommends
screening of patients at high risk for chlamydia but indicates
that the optimal timing for screening is uncertain. The Guidelines
for Perinatal Care recommends that pregnant women at high
risk for chlamydia be screened for infection during the first
prenatal care visit and during the third trimester. Recommendations
to screen pregnant women for STDs are based on disease severity
and sequelae, prevalence in the population, costs, medicolegal
considerations (e.g., state laws), and other factors. The
screening recommendations in this report are broader (i.e.,
if followed, more women will be screened for more STDs than
would be screened by following other recommendations) and
are compatible with other CDC guidelines.
Adolescents
The
rates of many STDs are highest among adolescents. For example,
the reported rates of chlamydia and gonorrhea are highest
among females aged 15--19 years, and many persons acquire
HPV infection during their adolescent years. Among adolescents
with acute HBV infection, the most commonly reported risk
factors are having sexual contact with a chronically infected
person or with multiple sex partners, or reporting their sexual
preference as homosexual. As part of a comprehensive strategy
to eliminate HBV transmission in the United States, ACIP has
recommended that all children and adolescents be administered
HBV vaccine.
Younger
adolescents (i.e., persons aged <15 years) who are sexually
active are at particular risk for STDs, especially youth in
detention facilities, STD clinic patients, male homosexuals,
and injecting-drug users (IDUs). Adolescents are at higher
risk for STDs because they frequently have unprotected intercourse,
are biologically more susceptible to infection, are engaged
in sexual partnerships frequently of limited duration, and
face multiple obstacles to using health care. Several of these
issues can be addressed by clinicians who provide services
to adolescents. Clinicians can address adolescents' lack of
knowledge and awareness regarding the risks and consequences
of STDs by offering guidance concerning healthy sexual behavior
and, therefore, prevent the establishment of patterns of behavior
that can undermine sexual health.
With
a few exceptions, all adolescents in the United States can
legally consent to the confidential diagnosis and treatment
of STDs. In all 50 states and the District of Columbia, medical
care for STDs can be provided to adolescents without parental
consent or knowledge. In addition, in the majority of states,
adolescents can consent to HIV counseling and testing. Consent
laws for vaccination of adolescents differ by state. Several
states consider provision of vaccine similar to treatment
of STDs and provide vaccination services without parental
consent. Because of the crucial importance of confidentially,
health-care providers should follow policies that provide
confidentiality and comply with state laws for STD services.
Despite
the prevalence of STDs among adolescents, providers frequently
fail to inquire about sexual behavior, assess risk for STDs,
provide counseling on risk reduction, and screen for asymptomatic
infection during clinical encounters. The style and content
of counseling and health education on these sensitive subjects
should be adapted for adolescents. Discussions should be appropriate
for the patient's developmental level and should be aimed
at identifying risky behaviors (e.g., sex and drug-use behaviors).
Careful, nonjudgmental, and thorough counseling are particularly
vital for adolescents who might not acknowledge that they
engage in high-risk behaviors.
Children
Management
of children who have STDs requires close cooperation between
clinicians, laboratorians, and child-protection authorities.
Official investigations, when indicated, should be initiated
promptly. Some diseases (e.g., gonorrhea, syphilis, and chlamydia),
if acquired after the neonatal period, are virtually 100%
indicative of sexual contact. For other diseases (e.g., HPV
infection and vaginitis), the association with sexual contact
is not as clear (see Sexual Assault and STDs).
MSM
Some
MSM are at high risk for HIV infection and other viral and
bacterial STDs. The frequency of unsafe sexual practices and
the reported rates of bacterial STDs and incident HIV infection
have declined substantially in MSM from the 1980s through
the mid-1990s. However, during the previous 10 years, increased
rates of infectious syphilis, gonorrhea, and chlamydial infection
and of higher rates of unsafe sexual behaviors have been documented
among MSM in the United States and virtually all industrialized
countries. The effect of these behavioral changes on HIV transmission
has not been ascertained, but preliminary data suggest that
the incidence of HIV infection might be increasing among some
MSM. These adverse trends probably are related to changing
attitudes concerning HIV infection because of the effects
of improved HIV/AIDS therapy on quality of life and survival,
changing patterns of substance abuse, demographic shifts in
MSM populations, and changes in sex partner networks resulting
from new venues for partner acquisition.
Clinicians
should assess the risks of STDs for all male patients, including
a routine inquiry about the sex of patients' sex partners.
MSM, including those with HIV infection, should routinely
undergo nonjudgmental STD/HIV risk assessment and client-centered
prevention counseling to reduce the likelihood of acquiring
or transmitting HIV or other STDs. Clinicians should be familiar
with local community resources available to assist MSM at
high risk in facilitating behavioral change. Clinicians also
should routinely ask sexually active MSM about symptoms consistent
with common STDs, including urethral discharge, dysuria, genital
and perianal ulcers, regional lymphadenopathy, skin rash,
and anorectal symptoms consistent with proctitis. Clinicians
also should maintain a low threshold for diagnostic testing
of symptomatic patients.
Routine
laboratory screening for common STDs is indicated for all
sexually active MSM. The following screening recommendations
are based on preliminary data. These tests should be performed
at least annually for sexually active MSM, including men with
or without established HIV infection:
- HIV
serology, if HIV negative or not tested within the previous
year;
- syphilis
serology;
- a
test for urethral infection with N. gonorrhoeae and C. trachomatis
in men who have had insertive intercourse* during the preceding
year;
- a
test for rectal infection with N. gonorrhoeae and
C. trachomatis in men who have had receptive anal intercourse*
during the preceding year;
- a
test for pharyngeal infection with N. gonorrhoeae
in men who have acknowledged participation in receptive
oral intercourse* during the preceding year; testing for
C. trachomatis pharyngeal infection is not recommended.
In
addition, some specialists would consider type-specific serologic
tests for HSV-2, if infection status is unknown. Routine testing
for anal cytologic abnormalities or anal HPV infection is
not recommended until more data are available on the reliability
of screening methods, the safety of and response to treatment,
and programmatic considerations.
More
frequent STD screening (i.e., at 3--6 month intervals) is
indicated for MSM who have multiple or anonymous partners,
have sex in conjunction with illicit drug use, use methamphetamine,
or whose sex partners participate in these activities.
Vaccination
against hepatitis A and B is recommended for all MSM in whom
previous infection or immunization cannot be documented. Preimmunization
serologic testing might be considered to reduce the cost of
vaccinating MSM who are already immune to these infections,
but this testing should not be delay vaccination. Vaccinating
persons who are immune to HAV or HBV infection because of
previous infection or vaccination does not increase the risk
for vaccine-related adverse events (see Hepatitis B, Prevaccination
Antibody Screening).
Women
Who Have Sex with Women (WSW)
Few
data are available on the risk of STDs conferred by sex between
women, but transmission risk probably varies by the specific
STD and sexual practice (e.g., oral-genital sex, vaginal or
anal sex using hands, fingers, or penetrative sex items, and
oral-anal sex). Practices involving digital-vaginal or digital-anal
contact, particularly with shared penetrative sex items, present
a possible means for transmission of infected cervicovaginal
secretions. This possibility is most directly supported by
reports of metronidazole-resistant trichomoniasis and genotype-concordant
HIV transmitted sexually between women who reported these
behaviors and by the high prevalence of BV among monogamous
WSW. Transmission of HPV can occur with skin-to-skin or skin-to-mucosa
contact, which can occur during sex between women. HPV deoxyribonucleic
acid (DNA) has been detected through polymerase chain reaction
(PCR)-based methods from the cervix, vagina, and vulva in
13%--30% of WSW, and high- and low-grade squamous intraepithelial
lesions (SIL) have been detected on Pap tests in WSW who reported
no previous sex with men. However, the majority of self-identified
WSW (53%--99%) have had sex with men and might continue this
practice. Therefore, all women should undergo Pap test screening
using current national guidelines, regardless of sexual preference
or sexual practices.
HSV-2
genital transmission between female sex partners is probably
inefficient, but the relatively frequent practice of orogenital
sex among WSW might place them at higher risk for genital
infection with HSV-1. This hypothesis is supported by the
recognized association between HSV-1 seropositivity and previous
number of female partners among WSW. Transmission of syphilis
between female sex partners, probably through oral sex, has
been reported. Although the rate of transmission of C. trachomatis
between women is unknown, WSW who also have sex with men are
at risk and should undergo routine screening according to
guidelines.
|
HIV
Infection: Detection, Counseling, and Referral
|
Infection
with HIV produces a spectrum of disease that progresses from
a clinically latent or asymptomatic state to AIDS as a late
manifestation. The pace of disease progression varies. In
untreated patients, the time between infection with HIV and
the development of AIDS ranges from a few months to as long
as 17 years (median: 10 years). The majority of adults and
adolescents infected with HIV remain symptom-free for extended
periods, but viral replication is active during all stages
of infection and increases substantially as the immune system
deteriorates. In the absence of treatment, AIDS will develop
eventually in nearly all HIV-infected persons.
Improvements
in antiretroviral therapy and increasing awareness among both
patients and health-care providers of the risk factors associated
with HIV transmission have led to more testing for HIV and
earlier diagnosis, frequently before symptoms develop. However,
the conditions of nearly 40% of persons who acquire HIV infection
continue to be diagnosed late, within 1 year of acquiring
AIDS. Prompt diagnosis of HIV infection is essential for multiple
reasons. Treatments are available that slow the decline of
immune system function; use of these therapies has been associated
with substantial declines in HIV-associated morbidity and
mortality in recent years. HIV-infected persons who have altered
immune function are at increased risk for infections for which
preventive measures are available (e.g., Pneumocystis jiroveci
pneumonia, toxoplasma encephalitis [TE], disseminated Mycobacterium
avium complex [MAC] disease, tuberculosis [TB], and bacterial
pneumonia). Because of its effect on the immune system, HIV
affects the diagnosis, evaluation, treatment, and follow-up
of multiple other diseases and might affect the efficacy of
antimicrobial therapy for some STDs. Finally, the early diagnosis
of HIV enables health-care providers to counsel infected patients,
refer them to various support services, and help prevent HIV
transmission to others. Acutely infected persons might have
elevated HIV viral loads and, therefore, might be more likely
to transmit HIV to their partners.
Proper
management of HIV infection involves a complex array of behavioral,
psychosocial, and medical services. Although some services
might not be available in STD treatment facilities. Therefore,
referral to a health-care provider or facility experienced
in caring for HIV-infected patients is advised. Providers
working in STD-treatment facilities should be knowledgeable
about the options for referral available in their communities.
While receiving care in STD-treatment facilities, HIV-infected
patients should be educated about HIV infection and the various
options available for support services and HIV care.
A
detailed discussion of the multiple, complex services required
for management of HIV infection is beyond the scope of this
section; however, this information is available in other published
resources. In subsequent sections, this report provides information
regarding diagnostic testing for HIV infection, counseling
patients who have HIV infection, referral of patients for
support services, including medical care, and the management
of sex and injecting-drug partners in STD-treatment facilities.
In addition, the report discusses HIV infection during pregnancy
and in infants and children.
Detection
of HIV Infection: Screening and Diagnostic Testing
All
persons who seek evaluation and treatment for STDs should
be screened for HIV infection. Screening should be routine,
regardless of whether the patient is known or suspected to
have specific behavioral risks for HIV infection.
Consent
and Pretest Information
HIV
screening should be voluntary and conducted only with the
patient's knowledge and understanding that testing is planned.
Persons should be informed orally or in writing that HIV testing
will be performed unless they decline (i.e., opt-out screening).
Oral or written communications should include an explanation
of positive and negative test results, and patients should
be offered an opportunity to ask questions and to decline
testing.
Prevention
Counseling
Prevention
counseling does not need to be explicitly linked to the HIV-testing
process. However, some patients might be more likely to think
about HIV and consider their risks when undergoing an HIV
test. HIV testing might present an ideal opportunity to provide
or arrange for prevention counseling to assist with behavior
changes that can reduce risk for acquiring HIV infection.
Prevention counseling should be offered and encouraged in
all health-care facilities serving patients at high risk and
in those (e.g., STD clinics) where information on HIV-risk
behaviors is routinely elicited.
Diagnostic
Testing
HIV
infection usually is diagnosed by tests for antibodies against
HIV-1. Some combination tests also detect antibodies against
HIV-2 (i.e., HIV-1/2). Antibody testing begins with a sensitive
screening test (e.g., the enzyme immunoassay [EIA] or rapid
test). The advent of HIV rapid testing has enabled clinicians
to make a substantially accurate presumptive diagnosis of
HIV-1 infection within half an hour. This testing can facilitate
the identification of the more than 250,000 persons living
with undiagnosed HIV in the United States. Reactive screening
tests must be confirmed by a supplemental test (e.g., the
Western blot [WB]) or an immunofluorescence assay (IFA). If
confirmed by a supplemental test, a positive antibody test
result indicates that a person is infected with HIV and is
capable of transmitting the virus to others. HIV antibody
is detectable in at least 95% of patients within 3 months
after infection. Although a negative antibody test result
usually indicates that a person is not infected, antibody
tests cannot exclude recent infection.
The
majority of HIV infections in the United States are caused
by HIV-1. However, HIV-2 infection should be suspected in
persons who have epidemiologic risk factors, including being
from West Africa (where HIV-2 is endemic) or have sex partners
from endemic areas, have sex partners known to be infected
with HIV-2, or have received a blood transfusion or nonsterile
injection in a West African country. HIV-2 testing also is
indicated when clinical evidence of HIV exists but tests for
HIV-1 antibodies or HIV-1 viral load are not positive, or
when HIV-1 WB results include the unusual indeterminate pattern
of gag plus pol bands in the absence of env bands.
Health-care
providers should be knowledgeable about the symptoms and signs
of acute retroviral syndrome, which is characterized by fever,
malaise, lymphadenopathy, and skin rash. This syndrome frequently
occurs in the first few weeks after HIV infection, before
antibody test results become positive. Suspicion of acute
retroviral syndrome should prompt nucleic acid testing (HIV
plasma ribonucleic acid [RNA]) to detect the presence of HIV,
although not all nucleic acid tests are approved for diagnostic
purposes; a positive HIV nucleic acid test should be confirmed
by subsequent antibody testing to document seroconversion
(using standard methods, EIA, and WB). Acutely infected patients
might be highly contagious because of increased plasma and
genital HIV RNA concentrations and might be continuing to
engage in risky behaviors. Current guidelines suggest that
persons with recently acquired HIV infection might benefit
from antiretroviral drugs and be candidates for clinical trials.
Therefore, patients with acute HIV infection should be referred
immediately to an HIV clinical care provider.
Diagnosis
of HIV infection should prompt efforts to reduce the risk
behavior that resulted in HIV infection and could result in
transmission of HIV to others. Early counseling and education
are particularly important for persons with recently acquired
infection because HIV plasma RNA levels are characteristically
high during this phase of infection and probably constitute
an increased risk for HIV transmission. The following are
specific recommendations for diagnostic testing for HIV infection:
- HIV
screening is recommended for all persons who seek evaluation
and treatment for STDs.
- HIV
testing must be voluntary.
- Consent
for HIV testing should be incorporated into the general
consent for care (verbally or in writing) with an opportunity
to decline (opt-out screening).
- HIV
rapid testing must be considered, especially in clinics
where a high proportion of patients do not return for HIV
test results.
- Positive
screening tests for HIV antibody must be confirmed by a
supplemental test (e.g., WB or IFA) before being considered
diagnostic of HIV infection.
- Persons
who have positive HIV test results (screening and confirmatory)
must receive initial HIV prevention counseling before leaving
the testing site. Such persons should 1) receive a medical
evaluation and, if indicated, behavioral and psychological
services, or 2) be referred for these services.
- Providers
should be alert to the possibility of acute retroviral syndrome
and should perform nucleic acid testing for HIV, if indicated.
Patients suspected of having recently acquired HIV infection
should be referred for immediate consultation with a specialist.
Counseling
for Patients with HIV Infection and Referral to Support Services
Persons
can be expected to be distressed when first informed of a
positive HIV test result. Such persons face multiple major
adaptive challenges, including
1) accepting the possibility of a shortened life span,
2) coping with the reactions of others to a stigmatizing illness,
3) developing and adopting strategies for maintaining physical
and emotional health, and
4) initiating changes in behavior to prevent HIV transmission
to others.
Many
persons will require assistance with making reproductive choices,
gaining access to health services, confronting possible employment
or housing discrimination, and coping with changes in personal
relationships. Therefore, behavioral and psychosocial services
are an integral part of health care for HIV-infected persons.
Such services should be available on site or through referral
when HIV infection is diagnosed. A comprehensive discussion
of specific recommendations is available in the Guidelines
for HIV Counseling, Testing, and Referral and Revised Recommendations
for HIV Screening of Pregnant Women. Innovative and successful
interventions to decrease risk taking by HIV-infected patients
have been developed for diverse populations.
Practice
settings for offering HIV care differ depending on local resources
and needs. Primary care providers and outpatient facilities
should ensure that appropriate resources are available for
each patient to avoid fragmentation of care. Although a single
source that is capable of providing comprehensive care for
all stages of HIV infection is preferred, the limited availability
of such resources frequently results in the need to coordinate
care among medical and social service providers in different
locations. Providers should avoid long delays between diagnosis
of HIV infection and access to additional medical and psychosocial
services. The use of HIV rapid testing can help avoid unnecessary
delays.
Recently
identified HIV infection might not have been recently acquired.
Persons newly diagnosed with HIV might be at any stage of
infection. Therefore, health-care providers should be alert
for symptoms or signs that suggest advanced HIV infection
(e.g., fever, weight loss, diarrhea, cough, shortness of breath,
and oral candidiasis). The presence of any of these symptoms
should prompt urgent referral for specialty medical care.
Similarly, providers should be alert for signs of psychologic
distress and be prepared to refer patients accordingly.
Diagnosis
of HIV infection reinforces the need to counsel patients regarding
high-risk behaviors because the consequences of such behaviors
include the risk for acquiring additional STDs and for transmitting
HIV (and other STDs) to other persons. Such attention to behaviors
in HIV-infected persons is consistent with national strategies
for HIV prevention. Providers should refer patients for prevention
counseling and risk-reduction support concerning high-risk
behaviors (e.g., substance abuse and high-risk sexual behaviors).
In multiple recent studies, researchers have developed successful
prevention interventions for different HIV-infected populations
that can be adapted to individuals.
Persons
with newly diagnosed HIV infection who receive care in the
STD treatment setting should be educated concerning what to
expect as they enter medical care for HIV infection. In nonemergent
situations, the initial evaluation of HIV-positive patients
usually includes the following:
- a
detailed medical history, including sexual and substance
abuse history; vaccination history; previous STDs; and specific
HIV-related symptoms or diagnoses;
- a
physical examination, including a gynecologic examination
for women;
- testing
for N. gonorrhoeae and C. trachomatis (and for women, a
Pap test and wet mount examination of vaginal secretions);
- complete
blood and platelet counts and blood chemistry profile;
- toxoplasma
antibody test;
- tests
for antibodies to HCV; testing for previous or present HAV
or HBV infection is recommended if determined to be cost-effective
before considering vaccination (see Hepatitis A and Hepatitis
B);
- syphilis
serology;
- a
CD4 T-lymphocyte analysis and determination of HIV plasma
viral load;
- a
tuberculin skin test (sometimes referred to as a purified
protein derivative);
- a
urinalysis; and
- a
chest radiograph.
Some
specialists recommend type-specific testing for HSV-2 if herpes
infection status is unknown. A first dose of hepatitis A and/or
hepatitis B vaccination for previously unvaccinated persons
for whom vaccine is recommended (see Hepatitis A and Hepatitis
B) should be administered at this first visit.
In
subsequent visits, when the results of laboratory and skin
tests are available, antiretroviral therapy may be offered,
if indicated, after initial antiretroviral resistance testing
is performed and specific prophylactic medications are administered
to reduce the incidence of opportunistic infections (e.g.,
Pneumocystis jiroveci pneumonia, TE, disseminated MAC infection,
and TB). The vaccination series for hepatitis A and/or B should
be offered for those in whom vaccination is recommended. Influenza
vaccination should be offered annually, and pneumococcal vaccination
should be given if it has not been administered in the previous
5 years.
Providers
should be alert to the possibility of new or recurrent STDs
and should treat such conditions aggressively. The occurrence
of an STD in an HIV-infected person is an indication of high-risk
behavior and should prompt referral for counseling. Because
many STDs are asymptomatic, routine screening for curable
STDs (e.g., syphilis, gonorrhea, and chlamydia) should be
performed at least yearly for sexually active persons. Women
should be screened for cervical cancer precursor lesions by
annual Pap smears. More frequent STD screening might be appropriate
depending on individual risk behaviors, the local epidemiology
of STDs, and whether incident STDs are detected by screening
or by the presence of symptoms.
Newly
diagnosed HIV-infected persons should receive or be referred
for a thorough psychosocial evaluation, including ascertainment
of behavioral factors indicating risk for transmitting HIV.
Patients might require referral for specific behavioral intervention
(e.g., a substance abuse program), mental health disorders
(e.g., depression), or emotional distress. They might require
assistance with securing and maintaining employment and housing.
Women should be counseled or appropriately referred regarding
reproductive choices and contraceptive options. Patients with
multiple psychosocial problems might be candidates for comprehensive
risk-reduction counseling and services.
The
following are specific recommendations for HIV counseling
and referral:
- Persons
who test positive for HIV antibody should be counseled,
either on site or through referral, concerning the behavioral,
psychosocial, and medical implications of HIV infection.
- Health-care
providers should be alert for medical or psychosocial conditions
that require immediate attention.
- Providers
should assess whether newly diagnosed patients' need for
immediate medical care or support should and link them to
services in which health-care personnel are experienced
in providing care for HIV-infected persons. Such persons
might need medical care or services for substance abuse,
mental health disorders, emotional distress, reproductive
counseling, risk-reduction counseling, and case management.
Providers should follow-up to ensure that patients have
received the needed services.
- Patients
should be educated regarding what to expect in follow-up
medical care.
Several
innovative interventions for HIV prevention have been developed
for diverse at-risk populations, and these can be locally
replicated or adapted. Involvement of nongovernment organizations
and community-based organizations might complement such efforts
in the clinical setting.
Management
of Sex Partners and Injecting-Drug Partners
Clinicians
evaluating HIV-infected persons should collect information
to determine whether any partners should be notified concerning
possible exposure to HIV. When referring to persons who are
infected with HIV, the term "partner" includes not
only sex partners but also IDUs who share syringes or other
injection equipment. The rationale for partner notification
is that the early diagnosis and treatment of HIV infection
in these partners might reduce morbidity and provides the
opportunity to encourage risk-reducing behaviors. Partner
notification for HIV infection should be confidential and
depends on the voluntary cooperation of the patient. Specific
guidance regarding spousal notification may vary by jurisdiction.
Two
complementary notification processes, patient referral and
provider referral, can be used to identify partners. With
patient referral, patients directly inform their partners
of their exposure to HIV infection. With provider referral,
trained health department personnel locate partners on the
basis of the names, descriptions, and addresses provided by
the patient. During the notification process, the confidentiality
of patients is protected; their names are not revealed to
partners who are notified. Many state and local health departments
provide these services.
The
following are specific recommendations for implementing partner-notification
procedures:
- HIV-infected
patients should be encouraged to notify their partners and
to refer them for counseling and testing. If requested by
the patient, health-care providers should assist in this
process, either directly or by referral to health department
partner-notification programs.
- If
patients are unwilling to notify their partners or if they
cannot ensure that their partners will seek counseling,
physicians or health department personnel should use confidential
partner notification procedures.
- Partners
who are contacted within 72 hours of a high-risk sexual
or injecting-drug exposure to an HIV-infected partner, which
involves exposure to genital secretions and/or blood, should
be offered PEP with combination antiretroviral therapy to
complete a 28-day course
Special
Considerations
Pregnancy.
All pregnant women in the United States should be tested for
HIV infection as early during pregnancy as possible. Testing
should occur after the patient is notified that she will be
tested for HIV as part of the routine panel of prenatal tests,
unless she declines (i.e., opt-out screening). For women who
decline, providers should continue to strongly encourage testing
and address concerns that pose obstacles to testing. Women
who decline testing because they have had a previous negative
HIV test should be informed of the importance of retesting
during each pregnancy. Testing pregnant women is particularly
important, not only to maintain the health of the patient,
but also because interventions (i.e., antiretroviral and obstetrical)
can reduce the risk of perinatal transmission of HIV.
After
pregnant women have been identified as being HIV-infected,
they should be educated about the risk of perinatal infection.
Evidence indicates that, in the absence of antiretroviral
and other interventions, 15%--25% of infants born to HIV-infected
mothers will become infected with HIV; such evidence also
indicates that an additional 12%--14% will become infected
during breastfeeding where HIV-infected women breastfeed their
infants into the second year of life.
The
risk of perinatal HIV transmission can be reduced substantially
to <2% through the use of antiretroviral regimens and obstetrical
interventions (i.e., zidovudine or nevirapine and elective
cesarean section at 38 weeks of pregnancy) and by avoiding
breastfeeding. Pregnant women who are HIV infected should
be counseled concerning their options (either on-site or by
referral), given appropriate antenatal treatment, and advised
not to breastfeed their infants (for women living in the United
States, where infant formula is readily available and can
be safely prepared).
HIV
Infection Among Infants and Children
Diagnosis
of HIV infection in a pregnant woman indicates the need to
consider whether other children of the woman might be infected.
Infants and young children with HIV infection differ from
adults and adolescents with respect to the diagnosis, clinical
presentation, and management of HIV disease. For example,
because maternal HIV antibody passes through the placenta,
antibody tests for HIV are expected to be positive in the
sera of both infected and uninfected infants born to seropositive
mothers. A definitive determination of HIV infection for an
infant aged <18 months is usually based on HIV nucleic
acid testing. Management of infants, children, and adolescents
who are known or suspected to be infected with HIV requires
referral to physicians familiar with the manifestations and
treatment of pediatric HIV infection.
|
Diseases
Characterized by Genital Ulcers
|
Management
of Patients Who Have Genital Ulcers
In
the United States, the majority of young, sexually active
patients who have genital ulcers have either genital herpes,
syphilis, or chancroid. The frequency of each condition differs
by geographic area and patient population; however, genital
herpes is the most prevalent of these diseases. More than
one of these diseases can be present in a patient who has
genital ulcers. All three of these diseases has been associated
with an increased risk for HIV infection. Not all genital
ulcers are caused by sexually transmitted infections.
A
diagnosis based only on the patient's medical history and
physical examination frequently is inaccurate. Therefore,
all patients who have genital ulcers should be evaluated with
a serologic test for syphilis and a diagnostic evaluation
for genital herpes; in settings where chancroid is prevalent,
a test for Haemophilus ducreyi should also be performed. Specific
tests for evaluation of genital ulcers include
1) syphilis serology and either darkfield examination or
direct immunofluorescence test for T. pallidum;
2) culture or antigen test for HSV; and
3) culture for H. ducreyi.
No
FDA-cleared PCR test for these organisms is available in the
United States; however, such testing can be performed by clinical
laboratories that have developed their own tests and conducted
a Clinical Laboratory Improvement Amendment (CLIA) verification
study. Type-specific serology for HSV-2 might be helpful in
identifying persons with genital herpes (see Genital Herpes,
Type-Specific Serologic Tests). Biopsy of genital ulcers might
be helpful in identifying the cause of ulcers that are unusual
or that do not respond to initial therapy. HIV testing should
be performed on all patients who have genital ulcers caused
by T. pallidum or H. ducreyi, and should be strongly considered
for those who have genital ulcers caused by HSV (see Diagnostic
Considerations, sections, Syphilis, Chancroid, and Genital
Herpes Simplex Virus).
Health-care
providers frequently must treat patients before test results
are available because early treatment decreases the possibility
of ongoing transmission and because successful treatment of
genital herpes depends on prompt initiation of therapy. The
clinician should treat for the diagnosis considered most likely,
on the basis of clinical presentation and epidemiologic circumstances.
In some instances, treatment must be initiated for additional
conditions because of diagnostic uncertainty. Even after complete
diagnostic evaluation, at least 25% of patients who have genital
ulcers have no laboratory-confirmed diagnosis.
Chancroid
In
the United States, chancroid usually occurs in discrete outbreaks,
although the disease is endemic in some areas. Chancroid is
a cofactor for HIV transmission, as are genital herpes and
syphilis; high rates of HIV infection among patients who have
chancroid occur in the United States and other countries.
Approximately 10% of persons who have chancroid that was acquired
in the United States are coinfected with T. pallidum or HSV;
this percentage is higher in persons who have acquired chancroid
outside the United States.
A
definitive diagnosis of chancroid requires the identification
of H. ducreyi on special culture media that is not widely
available from commercial sources; even when these media are
used, sensitivity is <80%. No FDA-cleared PCR test for
H. ducreyi is available in the United States, but such testing
can be performed by clinical laboratories that have developed
their own PCR test and conducted a CLIA verification study.
The
combination of a painful genital ulcer and tender suppurative
inguinal adenopathy suggests the diagnosis of chancroid. A
probable diagnosis of chancroid, for both clinical and surveillance
purposes, can be made if all of the following criteria are
met:
1) the patient has one or more painful genital ulcers;
2) the patient has no evidence of T. pallidum infection by
darkfield examination of ulcer exudate or by a serologic test
for syphilis
performed at least 7 days after onset
of ulcers;
3) the clinical presentation, appearance of genital ulcers
and, if present, regional lymphadenopathy are typical for
chancroid; and
4) a test for HSV performed on the ulcer exudate is negative.
Treatment
Successful
treatment for chancroid cures the infection, resolves the
clinical symptoms, and prevents transmission to others. In
advanced cases, scarring can result, despite successful therapy.
Recommended
Regimens*
Azithromycin 1 g orally in a single dose
OR
Ceftriaxone 250 mg intramuscularly (IM) in a single dose
OR
Ciprofloxacin 500 mg orally twice a day for 3 days
OR
Erythromycin base 500 mg orally three times a day for 7 days
*
Ciprofloxacin is contraindicated for pregnant and lactating
women. Azithromycin and ceftriaxone offer the advantage of
single-dose therapy. Worldwide, several isolates with intermediate
resistance to either ciprofloxacin or erythromycin have been
reported.
Other
Management Considerations
Male
patients who are uncircumcised and patients with HIV infection
do not respond as well to treatment as those who are circumcised
or HIV negative. Patients should be tested for HIV infection
at the time chancroid is diagnosed. Patients should be retested
for syphilis and HIV 3 months after the diagnosis of chancroid,
if the initial test results were negative.
Follow-Up
Patients
should be reexamined 3--7 days after initiation of therapy.
If treatment is successful, ulcers usually improve symptomatically
within 3 days and objectively within 7 days after therapy.
If no clinical improvement is evident, the clinician must
consider whether
1) the diagnosis is correct,
2) the patient is coinfected with another STD,
3) the patient is infected with HIV,
4) the treatment was not used as instructed, or
5) the H. ducreyi strain causing the infection is resistant
to the prescribed antimicrobial.
The
time required for complete healing depends on the size of
the ulcer; large ulcers might require >2 weeks. In addition,
healing is slower for some uncircumcised men who have ulcers
under the foreskin. Clinical resolution of fluctuant lymphadenopathy
is slower than resolution for ulcers and might require needle
aspiration or incision and drainage. Although needle aspiration
of chancroid buboes is a simple procedure, incision and drainage
might be preferred because of a reduced need for repeat drainage
procedures.
Management
of Sex Partners
Sex
partners of patients who have chancroid should be examined
and treated, regardless of whether symptoms of the disease
are present, if they had sexual contact with the patient during
the 10 days preceding the patient's onset of symptoms.
Special
Considerations
Pregnancy
The
safety and efficacy of azithromycin for pregnant and lactating
women have not been established. Ciprofloxacin is contraindicated
during pregnancy and lactation. No adverse effects of chancroid
on pregnancy outcome have been reported.
HIV
Infection
HIV-infected
patients who have chancroid should be monitored closely because,
as a group, these patients are more likely to experience treatment
failure and to have ulcers that heal more slowly. HIV-infected
patients might require longer courses of therapy than those
recommended for HIV-negative patients, and treatment failures
can occur with any regimen. Because evidence is limited concerning
the therapeutic efficacy of the recommended ceftriaxone and
azithromycin regimens in HIV-infected patients, these regimens
should be used for such patients only if follow-up can be
ensured. Some specialists prefer the erythromycin 7-day regimen
for treating HIV-infected persons.
Genital
HSV Infections
Genital
herpes is a chronic, life-long viral infection. Two types
of HSV have been identified, HSV-1 and HSV-2. The majority
of cases of recurrent genital herpes are caused by HSV-2 although
HSV-1 might become more common as a cause of first episode
genital herpes. At least 50 million persons in the United
States have genital HSV infection.
The
majority of persons infected with HSV-2 have not been diagnosed
with genital herpes. Many such persons have mild or unrecognized
infections but shed virus intermittently in the genital tract.
The majority of genital herpes infections are transmitted
by persons unaware that they have the infection or who are
asymptomatic when transmission occurs.
Diagnosis
of HSV Infection
The
clinical diagnosis of genital herpes is both insensitive and
nonspecific. The classical painful multiple vesicular or ulcerative
lesions are absent in many infected persons. Up to 50% of
first-episode cases of genital herpes are caused by HSV-1,
but recurrences and subclinical shedding are much less frequent
for genital HSV-1 infection than genital HSV-2 infection.
Therefore, whether genital herpes is caused by HSV-1 or HSV-2
influences prognosis and counseling. Therefore, the clinical
diagnosis of genital herpes should be confirmed by laboratory
testing (66). Both virologic and type-specific serologic tests
for HSV should be available in clinical settings that provide
care for patients with STDs or those at risk for STDs.
Virologic
Tests
Isolation
of HSV in cell culture is the preferred virologic test for
patients who seek medical treatment for genital ulcers or
other mucocutaneous lesions. However, the sensitivity of culture
is low, especially for recurrent lesions, and declines rapidly
as lesions begin to heal. PCR assays for HSV DNA are more
sensitive and have been used instead of viral culture; however,
PCR tests are not FDA-cleared for testing of genital specimens.
PCR is the test of choice for detecting HSV in spinal fluid
for diagnosis of HSV infection of the central nervous system
(CNS). Viral culture isolates should be typed to determine
if HSV-1 or HSV-2 is the cause of the infection. Lack of HSV
detection (i.e., culture or PCR) does not indicate a lack
of HSV infection, as viral shedding is intermittent. The use
of cytologic detection of cellular changes of HSV infection
is an insensitive and nonspecific method of diagnosis, both
for genital lesions (i.e., Tzanck preparation) and for cervical
Pap smears and should not be relied upon.
Type-Specific
Serologic Tests
Both
type-specific and nontype-specific antibodies to HSV develop
during the first several weeks after infection and persist
indefinitely. Accurate type-specific HSV serologic assays
are based on the HSV-specific glycoprotein G2 (HSV-2) and
glycoprotein G1 (HSV-1). Such assays first became commercially
available in 1999, but older assays that do not accurately
distinguish HSV-1 from HSV-2 antibody (despite claims to the
contrary) remain on the market. Therefore, the serologic type-specific
glycoprotein G (gG)-based assays should be specifically requested
when serology is performed.
The
FDA-cleared glycoprotein G-based type-specific assays include
the laboratory-based assays HerpeSelect-1 enzyme-linked
immunosorbent assay (ELISA) immunoglobulin G (IgG) or HerpeSelect-2
ELISA IgG and HerpeSelect 1 and 2 Immunoblot IgG (Focus
Technology, Inc., Herndon, Virginia), and HSV-2 ELISA (Trinity
Biotech USA, Berkeley Heights, New Jersey). Two other assays,
Biokit HSV-2 and SureVue HSV-2 (Biokit USA, Lexington, Massachusetts,
and Fisher Scientific, Pittsburgh, Pennsylvania, respectively),
are point-of-care tests that provide results for HSV-2 antibodies
from capillary blood or serum during a clinic visit. The sensitivities
of these glycoprotein G type-specific tests for the detection
of HSV-2 antibody vary from 80%--98%, and false-negative results
might be more frequent at early stages of infection. The specificities
of these assays are >96%. False-positive results can occur,
especially in patients with a low likelihood of HSV infection.
Repeat or confirmatory testing might be indicated in some
settings, especially if recent acquisition of genital herpes
is suspected.
Because
nearly all HSV-2 infections are sexually acquired, the presence
of type-specific HSV-2 antibody implies anogenital infection
and education and counseling appropriate for persons with
genital herpes should be provided. The presence of HSV-1 antibody
alone is more difficult to interpret. The majority of persons
with HSV-1 antibody have oral HSV infection acquired during
childhood, which might be asymptomatic. However, acquisition
of genital HSV-1 appears to be increasing, and genital HSV-1
also might be asymptomatic. Lack of symptoms in an HSV-1 seropositive
person does not distinguish anogenital from orolabial or cutaneous
infection. Persons with HSV-1 infection, regardless of site
of infection, remain at risk for HSV-2 acquisition.
Type-specific
HSV serologic assays might be useful in the following scenarios:
1) recurrent genital symptoms or atypical symptoms with negative
HSV cultures;
2) a clinical diagnosis of genital herpes without laboratory
confirmation; and
3) a partner with genital herpes.
Some
specialists believe that HSV serologic testing should be included
in a comprehensive evaluation for STDs among persons with
multiple sex partners, HIV infection, and among MSM at increased
risk for HIV acquisition. Screening for HSV-1 or HSV-2 in
the general population is not indicated.
Principles
of Management of Genital Herpes
Antiviral
chemotherapy offers clinical benefits to the majority of symptomatic
patients and is the mainstay of management. Counseling regarding
the natural history of genital herpes, sexual and perinatal
transmission, and methods to reduce transmission is integral
to clinical management.
Systemic
antiviral drugs can partially control the signs and symptoms
of herpes episodes when used to treat first clinical and recurrent
episodes, or when used as daily suppressive therapy. However,
these drugs neither eradicate latent virus nor affect the
risk, frequency, or severity of recurrences after the drug
is discontinued. Randomized trials have indicated that three
antiviral medications provide clinical benefit for genital
herpes: acyclovir, valacyclovir, and famciclovir (72--80).
Valacyclovir is the valine ester of acyclovir and has enhanced
absorption after oral administration. Famciclovir also has
high oral bioavailability. Topical therapy with antiviral
drugs offers minimal clinical benefit, and its use is discouraged.
First
Clinical Episode of Genital Herpes
Many
persons with first-episode herpes have mild clinical manifestations
but later develop severe or prolonged symptoms. Therefore,
patients with initial genital herpes should receive antiviral
therapy.
Recommended
Regimens*
Acyclovir 400 mg orally three times a day for 7--10 days
OR
Acyclovir 200 mg orally five times a day for 7--10 days
OR
Famciclovir 250 mg orally three times a day for 7--10 days
OR
Valacyclovir 1 g orally twice a day for 7--10 days
· Treatment might be extended if healing is incomplete
after 10 days of therapy.
Established
HSV-2 infection
The
majority of patients with symptomatic, first-episode genital
HSV-2 infection subsequently experience recurrent episodes
of genital lesions; recurrences are less frequent after initial
genital HSV-1 infection. Intermittent asymptomatic shedding
occurs in persons with genital HSV-2 infection, even in those
with longstanding or clinically silent infection. Antiviral
therapy for recurrent genital herpes can be administered either
episodically to ameliorate or shorten the duration of lesions
or continuously as suppressive therapy to reduce the frequency
of recurrences. Many persons, including those with mild or
infrequent recurrent outbreaks, benefit from antiviral therapy;
therefore, options for treatment should be discussed. Some
persons might prefer suppressive therapy, which has the additional
advantage of decreasing the risk of genital HSV-2 transmission
to susceptible partners.
Suppressive
Therapy for Recurrent Genital Herpes
Suppressive
therapy reduces the frequency of genital herpes recurrences
by 70%--80% in patients who have frequent recurrences (i.e.,
>6 recurrences per year), and many patients report no symptomatic
outbreaks. Treatment also is effective in patients with less
frequent recurrences. Safety and efficacy have been documented
among patients receiving daily therapy with acyclovir for
as long as 6 years and with valacyclovir or famciclovir for
1 year. Quality of life frequently is improved in patients
with frequent recurrences who receive suppressive therapy,
compared with episodic treatment.
The
frequency of recurrent genital herpes outbreaks diminishes
over time in many patients, and the patient's psychological
adjustment to the disease might change. Therefore, periodically
during suppressive treatment (e.g., once a year), providers
should discuss the need to continue therapy with the patient.
Daily
treatment with valacyclovir 500 mg daily decreases the rate
of HSV-2 transmission in discordant, heterosexual couples
in which the source partner has a history of genital HSV-2
infection (82). Such couples should be encouraged to consider
suppressive antiviral therapy as part of a strategy to prevent
transmission, in addition to consistent condom use and avoidance
of sexual activity during recurrences. Suppressive antiviral
therapy probably reduces transmission when used by persons
who have multiple partners (including MSM) and by those who
are HSV-2 seropositive without a history of genital herpes.
Recommended
Regimens
Acyclovir 400 mg orally twice a day
OR
Famiciclovir 250 mg orally twice a day
OR
Valacyclovir 500 mg orally once a day
OR
Valacyclovir 1.0 g orally once a day
Valacyclovir
500 mg once a day might be less effective than other valacyclovir
or acyclovir dosing regimens in patients who have very frequent
recurrences (i.e., >10 episodes per year). Several studies
have compared valacyclovir or famciclovir with acyclovir.
The results of these studies suggest that valacyclovir and
famciclovir are comparable to acyclovir in clinical outcome.
Ease of administration and cost also are important considerations
for prolonged treatment.
Episodic
Therapy for Recurrent Genital Herpes
Effective
episodic treatment of recurrent herpes requires initiation
of therapy within 1 day of lesion onset or during the prodrome
that precedes some outbreaks. The patient should be provided
with a supply of drug or a prescription for the medication
with instructions to initiate treatment immediately when symptoms
begin.
Recommended
Regimens
Acyclovir 400 mg orally three times a day for 5 days
OR
Acyclovir 800 mg orally twice a day for 5 days
OR
Acyclovir 800 mg orally three times a day for 2 days
OR
Famciclovir 125 mg orally twice daily for 5 days
OR
Famciclovir 1000 mg orally twice daily for 1 day
OR
Valacyclovir 500 mg orally twice a day for 3 days
OR
Valacyclovir 1.0 g orally once a day for 5 days
Severe
Disease
Intravenous
(IV) acyclovir therapy should be provided for patients who
have severe HSV disease or complications that necessitate
hospitalization (e.g., disseminated infection, pneumonitis,
or hepatitis) or CNS complications (e.g., meningitis or encephalitis).
The recommended regimen is acyclovir 5--10 mg/kg body weight
IV every 8 hours for 2--7 days or until clinical improvement
is observed, followed by oral antiviral therapy to complete
at least 10 days of total therapy.
Counseling
Counseling
of infected persons and their sex partners is critical to
the management of genital herpes. The goal of counseling is
to
1) help patients cope with the infection and
2) prevent sexual and perinatal transmission (8).
Although
initial counseling can be provided at the first visit, many
patients benefit from learning about the chronic aspects of
the disease after the acute illness subsides. Multiple resources,
including websites (http://www.ashastd.org
and http://www.ihmf.org)
and printed materials are available to assist patients, their
partners, and clinicians in counseling.
HSV-infected
persons might express anxiety concerning genital herpes that
does not reflect the actual clinical severity of their disease;
the psychological effect of HSV infection frequently is substantial.
Common concerns regarding genital herpes include the severity
of initial clinical manifestations, recurrent episodes, sexual
relationships and transmission to sex partners, and ability
to bear healthy children. The misconception that HSV causes
cancer should be dispelled. The psychological effect of a
serologic diagnosis of HSV-2 infection in a person with asymptomatic
or unrecognized genital herpes appears small and transient.
The
following recommendations apply to counseling of persons with
HSV infection:
- Persons
who have genital herpes should be educated concerning the
natural history of the disease, with emphasis on the potential
for recurrent episodes, asymptomatic viral shedding, and
the attendant risks of sexual transmission.
- Persons
experiencing a first episode of genital herpes should be
advised that suppressive therapy is available and is effective
in preventing symptomatic recurrent episodes and that episodic
therapy sometimes is useful in shortening the duration of
recurrent episodes.
- All
persons with genital HSV infection should be encouraged
to inform their current sex partners that they have genital
herpes and to inform future partners before initiating a
sexual relationship.
- Sexual
transmission of HSV can occur during asymptomatic periods.
Asymptomatic viral shedding is more frequent in genital
HSV-2 infection than genital HSV-1 infection and is most
frequent during the first 12 months after acquiring HSV-2.
- All
persons with genital herpes should remain abstinent from
sexual activity with uninfected partners when lesions or
prodromal symptoms are present.
- The
risk of HSV-2 sexual transmission can be decreased by the
daily use of valacyclovir by the infected person.
- Recent
studies indicate that latex condoms, when used consistently
and correctly, might reduce the risk for genital herpes
transmission.
- Sex
partners of infected persons should be advised that they
might be infected even if they have no symptoms. Type-specific
serologic testing of asymptomatic partners of persons with
genital herpes is recommended to determine whether risk
for HSV acquisition exists.
- The
risk for neonatal HSV infection should be explained to all
persons, including men. Pregnant women and women of childbearing
age who have genital herpes should inform their providers
who care for them during pregnancy and those who will care
for their newborn infant. Pregnant women who are not infected
with HSV-2 should be advised to avoid intercourse during
the third trimester with men who have genital herpes. Similarly,
pregnant women who are not infected with HSV-1 should be
counseled to avoid genital exposure to HSV-1 during the
third trimester (e.g., oral sex with a partner with oral
herpes and vaginal intercourse with a partner with genital
HSV-1 infection).
- Asymptomatic
persons diagnosed with HSV-2 infection by type-specific
serologic testing should receive the same counseling messages
as persons with symptomatic infection. In addition, such
persons should be taught about the clinical manifestations
of genital herpes.
Management
of Sex Partners
The
sex partners of patients who have genital herpes can benefit
from evaluation and counseling. Symptomatic sex partners should
be evaluated and treated in the same manner as patients who
have genital lesions. Asymptomatic sex partners of patients
who have genital herpes should be questioned concerning histories
of genital lesions and offered type-specific serologic testing
for HSV infection.
Special
Considerations
Allergy,
Intolerance, and Adverse Reactions
Allergic
and other adverse reactions to acyclovir, valacyclovir, and
famciclovir are rare. Desensitization to acyclovir has been
described (85).
HIV Infection
Immunocompromised
patients might have prolonged or severe episodes of genital,
perianal, or oral herpes. Lesions caused by HSV are common
among HIV-infected patients and might be severe, painful,
and atypical. HSV shedding is increased in HIV-infected persons.
Whereas antiretroviral therapy reduces the severity and frequency
of symptomatic genital herpes, frequent subclinical shedding
still occurs. Suppressive or episodic therapy with oral antiviral
agents is effective in decreasing the clinical manifestations
of HSV among HIV-positive persons. HIV-infected persons are
likely to be more contagious for HSV; the extent to which
suppressive antiviral therapy will decrease HSV transmission
from this population is unknown. Some specialists suggest
that HSV type-specific serologies be offered to HIV-positive
persons during their initial evaluation, and that suppressive
antiviral therapy be considered in those who have HSV-2 infection.
Recommended
Regimens for Daily Suppressive Therapy in Persons Infected
with HIV
Acyclovir 400--800 mg orally twice to three times a day
OR
Famciclovir 500 mg orally twice a day
OR
Valacyclovir 500 mg orally twice a day
Recommended
Regimens for Episodic Infection in Persons Infected with HIV
Acyclovir 400 mg orally three times a day for 5--10 days
OR
Famiciclovir 500 mg orally twice a day for 5--10 days
OR
Valacyclovir 1.0 grams orally twice a day for 5--10 days
Acyclovir,
valacyclovir, and famciclovir are safe for use in immunocompromised
patients in the doses recommended for treatment of genital
herpes. For severe HSV disease, initiating therapy with acyclovir
5--10 mg/kg body weight IV every 8 hours might be necessary.
If
lesions persist or recur in a patient receiving antiviral
treatment, HSV resistance should be suspected and a viral
isolate should be obtained for sensitivity testing (90). Such
patients should be managed in consultation with an HIV specialist,
and alternate therapy should be administered. All acyclovir-resistant
strains are resistant to valacyclovir, and the majority are
resistant to famciclovir. Foscarnet, 40 mg/kg body weight
IV every 8 hours until clinical resolution is attained, is
frequently effective for treatment of acyclovir-resistant
genital herpes. Topical cidofovir gel 1% applied to the lesions
once daily for 5 consecutive days also might be effective.
This preparation is not commercially available and must be
compounded at a pharmacy.
Genital
Herpes in Pregnancy
The
majority of mothers of infants who acquire neonatal herpes
lack histories of clinically evident genital herpes. The risk
for transmission to the neonate from an infected mother is
high (30%--50%) among women who acquire genital herpes near
the time of delivery and is low (<1%) among women with
histories of recurrent herpes at term or who acquire genital
HSV during the first half of pregnancy. However, because recurrent
genital herpes is much more common than initial HSV infection
during pregnancy, the proportion of neonatal HSV infections
acquired from mothers with recurrent herpes is substantial.
Prevention of neonatal herpes depends both on preventing acquisition
of genital HSV infection during late pregnancy and avoiding
exposure of the infant to herpetic lesions during delivery.
Women
without known genital herpes should be counseled to avoid
intercourse during the third trimester with partners known
or suspected of having genital herpes. In addition, pregnant
women without known orolabial herpes should be advised to
avoid receptive oral sex during the third trimester with partners
known or suspected to have orolabial herpes. Some specialists
believe that type-specific serologic tests are useful to identify
pregnant women at risk for HSV infection and to guide counseling
regarding the risk for acquiring genital herpes during pregnancy.
Such testing should be offered to women without genital herpes
whose sex partner has HSV infection. The effectiveness of
antiviral therapy to decrease the risk for HSV transmission
to pregnant women has not been studied.
All
pregnant women should be asked whether they have a history
of genital herpes. At the onset of labor, all women should
be questioned carefully about symptoms of genital herpes,
including prodromal symptoms, and all women should be examined
carefully for herpetic lesions. Women without symptoms or
signs of genital herpes or its prodrome can deliver vaginally.
The majority of specialists recommend that women with recurrent
genital herpetic lesions at the onset of labor deliver by
cesarean section to prevent neonatal herpes. However, cesarean
section does not completely eliminate the risk for HSV transmission
to the infant.
The
safety of systemic acyclovir, valacyclovir, and famciclovir
therapy in pregnant women has not been definitively established.
Available data do not indicate an increased risk for major
birth defects compared with the general population in women
treated with acyclovir during the first trimester (91). These
findings provide some assurance to women who have had prenatal
exposure to acyclovir. The experience with prenatal exposure
to valacyclovir and famciclovir is too limited to provide
useful information on pregnancy outcomes. Acyclovir may be
administered orally to pregnant women with first episode genital
herpes or severe recurrent herpes and should be administered
IV to pregnant women with severe HSV infection. Acyclovir
treatment late in pregnancy reduces the frequency of cesarean
sections among women who have recurrent genital herpes by
diminishing the frequency of recurrences at term, and many
specialists recommend such treatment. No data support the
use of antiviral therapy among HSV seropositive women without
a history of genital herpes. The risk for herpes is high in
infants of women who acquire genital HSV during late pregnancy;
such women should be managed in consultation with an infectious
diseases specialist. Some specialists recommend acyclovir
therapy in this circumstance, some recommend routine cesarean
section to reduce the risk for neonatal herpes, and others
recommend both.
Neonatal
Herpes
Infants
exposed to HSV during birth, as documented by maternal virologic
testing or presumed by observation of maternal lesions, should
be followed carefully in consultation with a specialist. Some
specialists recommend that such infants undergo surveillance
cultures of mucosal surfaces to detect HSV infection before
development of clinical signs of neonatal herpes. In addition,
some specialists recommend the use of acyclovir for infants
born to women who acquired HSV near term because the risk
for neonatal herpes is high for these infants. All infants
who have neonatal herpes should be promptly evaluated and
treated with systemic acyclovir. The recommended regimen for
infants treated for known or suspected neonatal herpes is
acyclovir 20 mg/kg body weight IV every 8 hours for 21 days
for disseminated and CNS disease or for 14 days for disease
limited to the skin and mucous membranes.
Granuloma
Inguinale (Donovanosis)
Granuloma
inguinale is a genital ulcerative disease caused by the intracellular
gram-negative bacterium Klebsiella granulomatis (formerly
known as Calymmatobacterium granulomatis). The disease occurs
rarely in the United States, although it is endemic in some
tropical and developing areas, including India; Papua, New
Guinea; central Australia; and southern Africa. Clinically,
the disease is commonly characterized as painless, progressive
ulcerative lesions without regional lymphadenopathy. The lesions
are highly vascular (i.e., beefy red appearance) and bleed
easily on contact. However, the clinical presentation also
can include hypertrophic, necrotic, or sclerotic variants.
The causative organism is difficult to culture, and diagnosis
requires visualization of dark-staining Donovan bodies on
tissue crush preparation or biopsy. No FDA-cleared PCR tests
for the detection of K. granulomatis DNA exist, but such an
assay might be useful if a CLIA verification study has been
conducted. The lesions might develop secondary bacterial infection
or can coexist with other sexually transmitted pathogens.
Treatment
A
limited number of studies on Donovanosis treatment have been
published. Treatment halts progression of lesions, although
prolonged therapy is usually required to permit granulation
and reepithelialization of the ulcers. Healing typically proceeds
inward from the ulcer margins. Relapse can occur 6--18 months
after apparently effective therapy. Several antimicrobial
regimens have been effective, but a limited number of controlled
trials have been published.
Recommended
Regimen
Doxycycline 100 mg orally twice a day for at least 3 weeks
and until all lesions have completely healed
Alternative Regimens
Azithromycin 1 g orally once per week for at least 3 weeks
and until all lesions have completely healed
OR
Ciprofloxacin 750 mg orally twice a day for at least 3 weeks
and until all lesions have completely healed
OR
Erythromycin base 500 mg orally four times a day for at least
3 weeks and until all lesions have completely healed
OR
Trimethoprim-sulfamethoxazole one double-strength (160 mg/800
mg) tablet orally twice a day for at least 3 weeks and until
all lesions have completely healed
Therapy
should be continued at least 3 weeks and until all lesions
have completely healed. Some specialists recommend the addition
of an aminoglycoside (e.g., gentamicin 1 mg/kg IV every 8
hours) to these regimens if improvement is not evident within
the first few days of therapy.
Follow-Up
Patients
should be followed clinically until signs and symptoms have
resolved.
Management
of Sex Partners
Persons
who have had sexual contact with a patient who has granuloma
inguinale within the 60 days before onset of the patient's
symptoms should be examined and offered therapy. However,
the value of empiric therapy in the absence of clinical signs
and symptoms has not been established.
Special
Considerations
Pregnancy
Pregnancy
is a relative contraindication to the use of sulfonamides.
Pregnant and lactating women should be treated with the erythromycin
regimen, and consideration should be given to the addition
of a parenteral aminoglycoside (e.g., gentamicin). Azithromycin
might prove useful for treating granuloma inguinale during
pregnancy, but published data are lacking. Doxycycline and
ciprofloxacin are contraindicated in pregnant
Persons
with both granuloma inguinale and HIV infection should receive
the same regimens as those who are HIV negative. Consideration
should be given to the addition of a parenteral aminoglycoside
(e.g., gentamicin).
Lymphogranuloma
Venereum
Lymphogranuloma
venereum (LGV) is caused by C. trachomatis serovars L1, L2,
or L3 (96). The most common clinical manifestation of LGV
among heterosexuals is tender inguinal and/or femoral lymphadenopathy
that is typically unilateral. A self-limited genital ulcer
or papule sometimes occurs at the site of inoculation. However,
by the time patients seek care, the lesions might have disappeared.
Rectal exposure in women or MSM might result in proctocolitis
(including mucoid and/or hemorrhagic rectal discharge, anal
pain, constipation, fever, and/or tenesmus). LGV is an invasive,
systemic infection, and if it is not treated early, LGV proctocolitis
might lead to chronic, colorectal fistulas and strictures.
Genital and colorectal LGV lesions might also develop secondary
bacterial infection or might be coinfected with other sexually
and nonsexually transmitted pathogens.
Diagnosis is based on clinical suspicion, epidemiologic information,
and the exclusion of other etiologies (of proctocolitis, inguinal
lymphadenopathy, or genital or rectal ulcers), along with
C. trachomatis testing, if available.
Genital
and lymph node specimens (i.e., lesion swab or bubo aspirate)
may be tested for C. trachomatis by culture, direct immunofluorescence,
or nucleic acid detection. Nucleic acid amplification tests
(NAAT) for C. trachomatis are not FDA-cleared for testing
rectal specimens. Additional procedures (e.g., genotyping)
are required for differentiating LGV from non-LGV C. trachomatis
but are not widely available.
Chlamydia
serology (complement fixation titers >1:64) can support
the diagnosis in the appropriate clinical context. Comparative
data between types of serologic tests are lacking, and the
diagnostic utility of serologic methods other than complement
fixation and some microimmunofluorescence procedures has not
been established. Serologic test interpretation for LGV is
not standardized, tests have not been validated for clinical
proctitis presentations, and C. trachomatis serovar-specific
serologic tests are not widely available.
In
the absence of specific LGV diagnostic testing, patients with
a clinical syndrome consistent with LGV, including proctocolitis
or genital ulcer disease with lymphadenopathy, should be treated
for LGV as described in this report.
Treatment
Treatment
cures infection and prevents ongoing tissue damage, although
tissue reaction to the injection can result in scarring. Buboes
might require aspiration through intact skin or incision and
drainage to prevent the formation of inguinal/femoral ulcerations.
Doxycycline is the preferred treatment.
Recommended
Regimen
Doxycycline 100 mg orally twice a day for 21 days
Alternative Regimen
Erythromycin base 500 mg orally four times a day for 21 days
Some
STD specialists believe that azithromycin 1.0 g orally once
weekly for 3 weeks is probably effective, although clinical
data are lacking.
Follow-Up
Patients
should be followed clinically until signs and symptoms have
resolved.
Management
of Sex Partners
Persons
who have had sexual contact with a patient who has LGV within
the 60 days before onset of the patient's symptoms should
be examined, tested for urethral or cervical chlamydial infection,
and treated with a standard chlamydia regimen (azithromycin
1 gm orally x 1 or doxycycline 100 mg orally twice a day for
7 days). The optimum contact interval is unknown; some specialists
use longer contact intervals.
Special
Considerations
Pregnancy
Pregnant
and lactating women should be treated with erythromycin. Azithromycin
might prove useful for treatment of LGV in pregnancy, but
no published data are available regarding its safety and efficacy.
Doxycycline is contraindicated in pregnant women.
HIV
Infection
Persons
with both LGV and HIV infection should receive the same regimens
as those who are HIV negative. Prolonged therapy might be
required, and delay in resolution of symptoms might occur.
General
Principles
Background
Syphilis
is a systemic disease caused by T. pallidum. Patients who
have syphilis might seek treatment for signs or symptoms of
primary infection (i.e., ulcer or chancre at the infection
site), secondary infection (i.e., manifestations that include,
but are not limited to, skin rash, mucocutaneous lesions,
and lymphadenopathy), or tertiary infection (e.g., cardiac
or ophthalmic manifestations, auditory abnormalities, or gummatous
lesions). Latent infections (i.e., those lacking clinical
manifestations) are detected by serologic testing. Latent
syphilis acquired within the preceding year is referred to
as early latent syphilis; all other cases of latent syphilis
are either late latent syphilis or latent syphilis of unknown
duration. Treatment for both late latent syphilis and tertiary
syphilis theoretically might require a longer duration of
therapy because organisms are dividing more slowly; however,
the validity of this concept has not been assessed.
Diagnostic
Considerations and Use of Serologic Tests
Darkfield
examinations and direct fluorescent antibody (DFA) tests of
lesion exudate or tissue are the definitive methods for diagnosing
early syphilis. A presumptive diagnosis is possible with the
use of two types of serologic tests:
1) nontreponemal tests (e.g., Venereal Disease Research Laboratory
[VDRL] and RPR) and
2) treponemal tests (e.g., fluorescent treponemal antibody
absorbed [FTA-ABS] and T. pallidum particle agglutination
[TP-PA]).
The use of only one type of serologic test
is insufficient for diagnosis because false-positive nontreponemal
test results are sometimes
associated with various medical conditions
unrelated to syphilis.
Nontreponemal
test antibody titers usually correlate with disease activity,
and results should be reported quantitatively. A fourfold
change in titer, equivalent to a change of two dilutions (e.g.,
from 1:16--1:4 or from 1:8--1:32), is considered necessary
to demonstrate a clinically significant difference between
two nontreponemal test results that were obtained using the
same serologic test. Sequential serologic tests in individual
patients should be performed by using the same testing method
(e.g., VDRL or RPR), preferably by the same laboratory. The
VDRL and RPR are equally valid assays, but quantitative results
from the two tests cannot be compared directly because RPR
titers frequently are slightly higher than VDRL titers. Nontreponemal
tests usually become nonreactive with time after treatment;
however, in some patients, nontreponemal antibodies can persist
at a low titer for a long period of time, sometimes for the
life of the patient. This response is referred to as the serofast
reaction.
The majority of patients who have reactive treponemal tests
will have reactive tests for the remainder of their lives,
regardless of treatment or disease activity. However, 15%--25%
of patients treated during the primary stage revert to being
serologically nonreactive after 2--3 years (97). Treponemal
test antibody titers do not correlate with disease activity
and should not be used to assess treatment response.
Some clinical laboratories and blood banks have begun to screen
samples using treponemal EIA tests (98). This strategy will
identify both persons with previous treatment and persons
with untreated or incompletely treated syphilis. False-positive
results can occur, particularly among populations with a low
prevalence of syphilis.
Persons
with a positive treponemal screening test should have a standard
nontreponemal test with titer to guide patient management
decisions. If the nontreponemal test is negative, then a different
treponemal test should be performed to confirm the results
of the initial test. If a second trepomenal test is positive,
treatment decisions should be discussed in consultation with
a specialist. Some HIV-infected patients can have atypical
serologic test results (i.e., unusually high, unusually low,
or fluctuating titers). For such patients, when serologic
tests do not correspond with clinical syndromes suggestive
of early syphilis, use of other tests (e.g., biopsy and direct
microscopy) should be considered. However, for the majority
of HIV-infected patients, serologic tests are accurate and
reliable for the diagnosis of syphilis and for following the
response to treatment.
No single test can be used to diagnose neurosyphilis. The
VDRL-cerebrospinal fluid (CSF) is highly specific, but it
is insensitive. The majority of other tests are both insensitive
and nonspecific and must be interpreted in relation to other
test results and the clinical assessment. Therefore, the diagnosis
of neurosyphilis usually depends on various combinations of
reactive serologic test results, CSF cell count or protein,
or a reactive VDRL-CSF with or without clinical manifestations.
The CSF leukocyte count usually is elevated (>5 white blood
cell count [WBC]/mm3) in patients with neurosyphilis; this
count also is a sensitive measure of the effectiveness of
therapy. The VDRL-CSF is the standard serologic test for CSF,
and when reactive in the absence of substantial contamination
of CSF with blood, it is considered diagnostic of neurosyphilis.
However, the VDRL-CSF might be nonreactive even when neurosyphilis
is present. Some specialists recommend performing an FTA-ABS
test on CSF. The CSF FTA-ABS is less specific (i.e., yields
more false-positive results) for neurosyphilis than the VDRL-CSF,
but the test is highly sensitive. Therefore, some specialists
believe that a negative CSF FTA-ABS test excludes neurosyphilis.
Treatment
Penicillin
G, administered parenterally, is the preferred drug for treatment
of all stages of syphilis. The preparation(s) used (i.e.,
benzathine, aqueous procaine, or aqueous crystalline), the
dosage, and the length of treatment depend on the stage and
clinical manifestations of the disease. However, neither combinations
of benzathine penicillin and procaine penicillin nor oral
penicillin preparations are considered appropriate for the
treatment of syphilis. Reports have indicated that inappropriate
use of combination benzathine-procaine penicillin (Bicillin
C-R®) instead of the standard benzathine penicillin product
widely used in the United States (Bicillin L-A®) has occurred.
Practitioners, pharmacists, and purchasing agents should be
aware of the similar names of these two products and avoid
use of the inappropriate combination therapy agent for treating
syphilis.
The
efficacy of penicillin for the treatment of syphilis was well
established through clinical experience even before the value
of randomized controlled clinical trials was recognized. Therefore,
nearly all the recommendations for the treatment of syphilis
are based on the opinions of persons knowledgeable about STDs
and are reinforced by case series, clinical trials, and 50
years of clinical experience.
Parenteral
penicillin G is the only therapy with documented efficacy
for syphilis during pregnancy. Pregnant women with syphilis
in any stage who report penicillin allergy should be desensitized
and treated with penicillin. Skin testing for penicillin allergy
might be useful in pregnant women; such testing also is useful
in other patients (see Management of Patients Who Have a History
of Penicillin Allergy).
The
Jarisch-Herxheimer reaction is an acute febrile reaction frequently
accompanied by headache, myalgia, and other symptoms that
usually occur within the first 24 hours after any therapy
for syphilis. Patients should be informed about this possible
adverse reaction. The Jarisch-Herxheimer reaction occurs most
frequently among patients who have early syphilis. Antipyretics
may be used, but they have not been proven to prevent this
reaction. The Jarisch-Herxheimer reaction might induce early
labor or cause fetal distress in pregnant women, but this
possibly should not prevent or delay therapy (see Syphilis
During Pregnancy).
Management
of Sex Partners
Sexual
transmission of T. pallidum occurs only when mucocutaneous
syphilitic lesions are present; such manifestations are uncommon
after the first year of infection. However, persons exposed
sexually to a patient who has syphilis in any stage should
be evaluated clinically and serologically and treated with
a recommended regimen, according to the following recommendations:
- Persons
who were exposed within the 90 days preceding the diagnosis
of primary, secondary, or early latent syphilis in a sex
partner might be infected even if seronegative; therefore,
such persons should be treated presumptively.
- Persons
who were exposed >90 days before the diagnosis of primary,
secondary, or early latent syphilis in a sex partner should
be treated presumptively if serologic test results are not
available immediately and the opportunity for follow-up
is uncertain.
- For
purposes of partner notification and presumptive treatment
of exposed sex partners, patients with syphilis of unknown
duration who have high nontreponemal serologic test titers
(i.e., >1:32) can be assumed to have early syphilis.
However, serologic titers should not be used to differentiate
early from late latent syphilis for the purpose of determining
treatment (see Latent Syphilis, Treatment).
- Long-term
sex partners of patients who have latent syphilis should
be evaluated clinically and serologically for syphilis and
treated on the basis of the evaluation findings.
For
identification of at-risk sexual partners, the periods before
treatment are
1) 3 months plus duration of symptoms for primary syphilis,
2) 6 months plus duration of symptoms for secondary syphilis,
and
3) 1 year for early latent syphilis.
Primary
and Secondary Syphilis
Treatment
Parenteral
penicillin G has been used effectively for more than 50 years
to achieve clinical resolution (i.e., healing of lesions and
prevention of sexual transmission) and to prevent late sequelae.
However, no comparative trials have been adequately conducted
to guide the selection of an optimal penicillin regimen (i.e.,
the dose, duration, and preparation). Substantially fewer
data are available for nonpenicillin regimens.
Recommended
Regimen for Adults*
Benzathine penicillin G 2.4 million units IM in a single dose
* Recommendations for treating HIV-infected persons and pregnant
women for syphilis have been discussed in this report (see
Syphilis, Special considerations and Syphilis in Pregnancy).
Recommended
Regimen for Children
After
the newborn period (aged >1 month), children with syphilis
should have a CSF examination to detect asymptomatic neurosyphilis,
and birth and maternal medical records should be reviewed
to assess whether such children have congenital or acquired
syphilis (see Congenital Syphilis). Children with acquired
primary or secondary syphilis should be evaluated (e.g., through
consultation with child-protection services) (see Sexual Assault
or Abuse of Children) and treated by using the following pediatric
regimen.
Benzathine
penicillin G 50,000 units/kg IM, up to the adult dose of 2.4
million units in a single dose
Other
Management Considerations
All
patients who have syphilis should be tested for HIV infection.
In geographic areas in which the prevalence of HIV is high,
patients who have primary syphilis should be retested for
HIV after 3 months if the first HIV test result was negative.
Patients
who have syphilis and symptoms or signs suggesting neurologic
disease (e.g., meningitis) or ophthalmic disease (e.g., uveitis,
iritis, neuroretinitis, or optic neuritis) should have an
evaluation that includes CSF analysis and ocular slit-lamp
examination. Treatment should be guided by the results of
this evaluation.
Invasion
of CSF by T. pallidum accompanied by CSF abnormalities is
common among adults who have primary or secondary syphilis.
However, neurosyphilis develops in only a limited number of
patients after treatment with the penicillin regimens recommended
for primary and secondary syphilis. Therefore, unless clinical
signs or symptoms of neurologic or ophthalmic involvement
are present, CSF analysis is not recommended for routine evaluation
of patients who have primary or secondary syphilis.
Follow-Up
Treatment
failure can occur with any regimen. However, assessing response
to treatment frequently is difficult, and definitive criteria
for cure or failure have not been established. Nontreponemal
test titers might decline more slowly for persons who previously
had syphilis. Patients should be reexamined clinically and
serologically 6 months and 12 months after treatment; more
frequent evaluation might be prudent if follow-up is uncertain.
Patients
who have signs or symptoms that persist or recur or who have
a sustained fourfold increase in nontreponemal test titer
(i.e., compared with the maximum or baseline titer at the
time of treatment) probably failed treatment or were reinfected.
These patients should be retreated and reevaluated for HIV
infection. Because treatment failure usually cannot be reliably
distinguished from reinfection with T. pallidum, a CSF analysis
also should be performed. Clinical trial data have demonstrated
that 15% of patients with early syphilis treated with the
recommended therapy will not achieve a two dilution decline
in nontreponemal titer used to define response at 1 year after
treatment.
Failure
of nontreponemal test titers to decline fourfold within 6
months after therapy for primary or secondary syphilis might
be indicative of probable treatment failure. Persons for whom
titers remain serofast should be reevaluated for HIV infection.
Optimal management of such patients is unclear. At a minimum,
these patients should receive additional clinical and serologic
follow-up. HIV-infected patients should be evaluated more
frequently (i.e., at 3-month intervals instead of 6-month
intervals). If additional follow-up cannot be ensured, re-treatment
is recommended. Because treatment failure might be the result
of unrecognized CNS infection, many specialists recommend
CSF examination in such situations.
For retreatment, the majority of STD specialists recommend
administering weekly injections of benzathine penicillin G
2.4 million units IM for 3 weeks, unless CSF examination indicates
that neurosyphilis is present. In rare instances, serologic
titers do not decline despite a negative CSF examination and
a repeated course of therapy. Additional therapy or repeated
CSF examinations are not warranted in these circumstances.
Management
of Sex Partners
See
General Principles, Management of Sex Partners.
Special
Considerations
Penicillin
Allergy. Data to support the use of alternatives to penicillin
in the treatment of early syphilis are limited. However, several
therapies might be effective in nonpregnant, penicillin-allergic
patients who have primary or secondary syphilis. Doxycycline
(100 mg orally twice daily for 14 days) and tetracycline (500
mg four times daily for 14 days) are regimens that have been
used for many years. Compliance is likely to be better with
doxycycline than tetracycline because tetracycline can cause
gastrointestinal side effects. Although limited clinical studies,
along with biologic and pharmacologic evidence, suggest that
ceftriaxone is effective for treating early syphilis, the
optimal dose and duration of ceftriaxone therapy have not
been defined. Some specialists recommend 1 g daily either
IM or IV for 8--10 days. Some patients who are allergic to
penicillin also might be allergic to ceftriaxone; in these
circumstances, use of an alternative agent might be required.
Preliminary data suggest that azithromycin might be effective
as a single oral dose of 2 g. However, several cases of azithromycin
treatment failure have been reported, and resistance to azithromycin
has been documented in several geographic areas. Close follow-up
of persons receiving alternative therapies is essential. The
use of any of these therapies in HIV-infected persons has
not been well-studied; therefore, the use of doxycycline,
ceftriaxone, and azithromycin among such persons must be undertaken
with caution.
Patients
with penicillin allergy whose compliance with therapy or follow-up
cannot be ensured should be desensitized and treated with
benzathine penicillin. Skin testing for penicillin allergy
might be useful in some circumstances in which the reagents
and expertise are available to perform the test adequately
(see Management of Patients Who Have a History of Penicillin
Allergy).
Pregnancy.
Pregnant patients who are allergic to penicillin should be
desensitized and treated with penicillin (see Management of
Patients Who Have a History of Penicillin Allergy and Syphilis
During Pregnancy).
HIV
Infection. See Syphilis Among HIV-Infected Persons.
Latent
Syphilis
Latent
syphilis is defined as syphilis characterized by seroreactivity
without other evidence of disease. Patients who have latent
syphilis and who acquired syphilis within the preceding year
are classified as having early latent syphilis. Patients'
conditions can be diagnosed as early latent syphilis if, within
the year preceding the evaluation, they had
1)
a documented seroconversion or fourfold or greater increase
in titer of a nontreponemal test;
2) unequivocal symptoms of primary or secondary syphilis;
3) a sex partner documented to have primary, secondary, or
early latent syphilis; or
4) reactive nontreponemal and treponemal tests from a person
whose only possible exposure occurred within the previous
12 months.
Nontreponemal
serologic titers usually are higher during early latent syphilis
than late latent syphilis. However, early latent syphilis
cannot be reliably distinguished from late latent syphilis
solely on the basis of nontreponemal titers. All patients
with latent syphilis should have careful examination of all
accessible mucosal surfaces (i.e., the oral cavity, the perineum
in women, and perianal area, underneath the foreskin in uncircumcised
men) to evaluate for internal mucosal lesions. All patients
who have syphilis should be tested for HIV infection.
Treatment
Treatment
of latent syphilis usually does not affect transmission and
is intended to prevent late complications. Although clinical
experience supports the effectiveness of penicillin in achieving
this goal, limited evidence is available for guidance in choosing
specific regimens.
The
following regimens are recommended for penicillin nonallergic
patients who have normal CSF examinations (if performed).
Recommended
Regimens for Adults
Early Latent Syphilis
Benzathine penicillin G 2.4 million units IM in a single dose
Late
Latent Syphilis or Latent Syphilis of Unknown Duration
Benzathine penicillin G 7.2 million units total, administered
as 3 doses of 2.4 million units IM each at 1-week intervals
After the newborn period, children with syphilis should have
a CSF examination to exclude neurosyphilis. In addition, birth
and maternal medical records should be reviewed to assess
whether children have congenital or acquired syphilis (see
Congenital Syphilis). Older children with acquired latent
syphilis should be evaluated as described for adults and treated
using the following pediatric regimens (see Sexual Assault
or Abuse of Children). These regimens are for penicillin nonallergic
children who have acquired syphilis and who have normal CSF
examination results.
Recommended
Regimens for Children
Early Latent Syphilis
Benzathine penicillin G 50,000 units/kg IM, up to the adult
dose of 2.4 million units in a single dose
Late Latent Syphilis or Latent Syphilis of Unknown Duration
Benzathine penicillin G 50,000 units/kg IM, up to the adult
dose of 2.4 million units, administered as 3 doses at 1-week
intervals (total 150,000 units/kg up to the adult total dose
of 7.2 million units)
Other
Management Considerations
All
persons who have latent syphilis should be evaluated clinically
for evidence of tertiary disease (e.g., aortitis and gumma)
and syphilitic ocular disease (e.g., iritis and uveitis).
Patients who have syphilis and who demonstrate any of the
following criteria should have a prompt CSF examination:
- neurologic
or ophthalmic signs or symptoms,
- evidence
of active tertiary syphilis (e.g., aortitis and gumma),
- treatment
failure, or
- HIV
infection with late latent syphilis or syphilis of unknown
duration.
If
dictated by circumstances and patient preferences, a CSF examination
may be performed for patients who do not meet these criteria.
Some specialists recommend performing a CSF examination on
all patients who have latent syphilis and a nontreponemal
serologic test of >1:32 or if the patient is HIV-infected
with a serum CD4 count <350. However, the likelihood of
neurosyphilis in this circumstance is unknown. If a CSF examination
is performed and the results indicate abnormalities consistent
with neurosyphilis, the patient should be treated for neurosyphilis
(see Neurosyphilis).
If
a patient misses a dose of penicillin in a course of weekly
therapy for late syphilis, the appropriate course of action
is unclear. Pharmacologic considerations suggest that an interval
of 10--14 days between doses of benzathine penicillin for
late syphilis or latent syphilis of unknown duration might
be acceptable before restarting the sequence of injections.
Missed doses are not acceptable for pregnant patients receiving
therapy for late latent syphilis; pregnant women who miss
any dose of therapy must repeat the full course of therapy.
Follow-Up
Quantitative
nontreponemal serologic tests should be repeated at 6, 12,
and 24 months. Patients with a normal CSF examination should
be re-treated for latent syphilis if
1)
titers increase fourfold,
2) an initially high titer (>1:32) fails to decline at
least fourfold (i.e., two dilutions) within 12--24 months
of therapy, or
3) signs or symptoms attributable to syphilis develop. In
rare instances, despite a negative CSF examination and a repeated
course of therapy, serologic titers
might still not decline. In these circumstances, the need
for additional therapy or repeated CSF examinations is unclear.
Management
of Sex Partners. See General Principles, Management of Sex
Partners.
Special
Considerations
Penicillin
Allergy. The effectiveness of alternatives to penicillin in
the treatment of latent syphilis has not been well-documented.
Nonpregnant patients allergic to penicillin who have clearly
defined early latent syphilis should respond to therapies
recommended as alternatives to penicillin for the treatment
of primary and secondary syphilis (see Primary and Secondary
Syphilis, Treatment). The only acceptable alternatives for
the treatment of late latent syphilis or latent syphilis of
unknown duration are doxycycline (100 mg orally twice daily)
or tetracycline (500 mg orally four times daily), both for
28 days. These therapies should be used only in conjunction
with close serologic and clinical follow-up. Limited clinical
studies, along with biologic and pharmacologic evidence, suggest
that ceftriaxone might be effective for treating late latent
syphilis or syphilis of unknown duration. However, the optimal
dose and duration of ceftriaxone therapy have not been defined,
and treatment decisions should be discussed in consultation
with a specialist. Some patients who are allergic to penicillin
also might be allergic to ceftriaxone; in these circumstances,
use of an alternative agent might be required. The efficacy
of these alternative regimens in HIV-infected persons has
not been well-studied and, therefore, must be considered with
caution.
Pregnancy
Pregnant
patients who are allergic to penicillin should be desensitized
and treated with penicillin (see Management of Patients Who
Have a History of Penicillin Allergy and Syphilis During Pregnancy).
HIV
Infection. See Syphilis Among HIV-Infected Persons.
Tertiary
Syphilis
Tertiary
syphilis refers to gumma and cardiovascular syphilis but not
to all neurosyphilis. Patients who are not allergic to penicillin
and have no evidence of neurosyphilis should be treated with
the following regimen.
Recommended
Regimen
Benzathine penicillin G 7.2 million units total, administered
as 3 doses of 2.4 million units IM each at 1-week intervals
Other
Management Considerations
Patients
who have symptomatic late syphilis should be given a CSF examination
before therapy is initiated. Some providers treat all patients
who have cardiovascular syphilis with a neurosyphilis regimen.
The complete management of patients who have cardiovascular
or gummatous syphilis is beyond the scope of these guidelines.
These patients should be managed in consultation with an infectious
diseases specialist.
Follow-Up
Limited
information is available concerning clinical response and
follow-up of patients who have tertiary syphilis.
Management
of Sex Partners. See General Principles, Management of Sex
Partners.
Special
Considerations
Penicillin
Allergy. Patients allergic to penicillin should be treated
according to treatment regimens recommended for late latent
syphilis.
Pregnancy.
Pregnant patients who are allergic to penicillin should be
desensitized, if necessary, and treated with penicillin (see
Management of Patients Who Have a History of Penicillin Allergy
and Syphilis During Pregnancy).
HIV
Infection. See Syphilis Among HIV-Infected Persons.
Neurosyphilis
Treatment
CNS
involvement can occur during any stage of syphilis. A patient
who has clinical evidence of neurologic involvement with syphilis
(e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic
or auditory symptoms, cranial nerve palsies, and symptoms
or signs of meningitis) should have a CSF examination.
Syphilitic
uveitis or other ocular manifestations frequently are associated
with neurosyphilis; patients with these symptoms should be
treated according to the recommendations for patients with
neurosyphilis. A CSF examination should be performed for all
such patients to identify those with abnormalities that require
follow-up CSF examinations to assess treatment response.
Patients
who have neurosyphilis or syphilitic eye disease (e.g., uveitis,
neuroretinitis, and optic neuritis) should be treated with
the following regimen.
Recommended
Regimen
Aqueous crystalline penicillin G 18--24 million units per
day, administered as 3--4 million units IV
every 4 hours or continuous infusion, for 10--14 days
If compliance with therapy can be ensured, patients may be
treated with the following alternative regimen.
Alternative Regimen
Procaine penicillin 2.4 million units IM once daily
PLUS
Probenecid 500 mg orally four times a day, both for 10--14
days
The durations of the recommended and alternative regimens
for neurosyphilis are shorter than that of the regimen used
for late syphilis in the absence of neurosyphilis. Therefore,
some specialists administer benzathine penicillin, 2.4 million
units IM once per week for up to 3 weeks after completion
of these neurosyphilis treatment regimens to provide a comparable
total duration of therapy.
Other
Management Considerations
Other
considerations in the management of patients who have neurosyphilis
are as follows:
- All
patients who have syphilis should be tested for HIV.
- Many
specialists recommend treating patients who have evidence
of auditory disease caused by syphilis in the same manner
as patients who have neurosyphilis, regardless of CSF examination
results. Although systemic steroids are used frequently
as adjunctive therapy for otologic syphilis, such drugs
have not been proven beneficial.
Follow-Up
If
CSF pleocytosis was present initially, a CSF examination should
be repeated every 6 months until the cell count is normal.
Follow-up CSF examinations also can be used to evaluate changes
in the VDRL-CSF or CSF protein after therapy; however, changes
in these two parameters occur more slowly than cell counts,
and persistent abnormalities might be less important. If the
cell count has not decreased after 6 months or if the CSF
is not normal after 2 years, re-treatment should be considered.
Recent data on HIV-infected persons with neurosyphilis suggest
that CSF abnormalities might persist for extended periods
in these persons, and close clinical follow-up is warranted
(105,106).
Management
of Sex Partners. See General Principles, Management of Sex
Partners.
Special
Considerations
Penicillin
Allergy. Ceftriaxone can be used as an alternative treatment
for patients with neurosyphilis, although the possibility
of cross-reactivity between this agent and penicillin exists.
Some specialists recommend ceftriaxone 2 g daily either IM
or IV for 10--14 days. Other regimens have not been adequately
evaluated for treatment of neurosyphilis. Therefore, if concern
exists regarding the safety of ceftriaxone for a patient with
neurosyphilis, the patient should obtain skin testing to confirm
penicillin allergy and, if necessary, be desensitized and
managed in consultation with a specialist.
Pregnancy.
Pregnant patients who are allergic to penicillin should be
desensitized, if necessary, and treated with penicillin (see
Syphilis During Pregnancy).
HIV
Infection. See Syphilis Among HIV-Infected Patients.
Syphilis
Among HIV-Infected Persons
Diagnostic
Considerations
Unusual
serologic responses have been observed among HIV-infected
persons who have syphilis. The majority of reports have involved
serologic titers that were higher than expected, but false-negative
serologic test results and delayed appearance of seroreactivity
also have been reported. However, unusual serologic responses
are uncommon, and the majority of specialists believe that
both treponemal and nontreponemal serologic tests for syphilis
can be interpreted in the usual manner for the majority of
patients who are coinfected with T. pallidum and HIV.
When
clinical findings are suggestive of syphilis but serologic
tests are nonreactive or their interpretation is unclear,
alternative tests (e.g., biopsy of a lesion, darkfield examination,
or DFA staining of lesion material) might be useful for diagnosis.
Neurosyphilis should be considered in the differential diagnosis
of neurologic disease in HIV-infected persons.
Treatment
Compared
with HIV-negative patients, HIV-positive patients who have
early syphilis might be at increased risk for neurologic complications
and might have higher rates of treatment failure with currently
recommended regimens. The magnitude of these risks is not
defined precisely but is likely minimal. No treatment regimens
for syphilis have been demonstrated to be more effective in
preventing neurosyphilis in HIV-infected patients than the
syphilis regimens recommended for HIV-negative patients (100).
Careful follow-up after therapy is essential.
Primary
and Secondary Syphilis Among HIV-Infected Persons
Treatment
Treatment
with benzathine penicillin G, 2.4 million units IM in a single
dose is recommended. Some specialists recommend additional
treatments (e.g., benzathine penicillin G administered at
1-week intervals for 3 weeks, as recommended for late syphilis)
in addition to benzathine penicillin G 2.4 million units IM.
Other
Management Considerations
Because
CSF abnormalities (e.g., mononuclear pleocytosis and elevated
protein levels) are common in patients with early syphilis
and in persons with HIV infection, the clinical and prognostic
significance of such CSF abnormalities in HIV-infected persons
with primary or secondary syphilis is unknown. Although the
majority of HIV-infected persons respond appropriately to
standard benzathine penicillin therapy, some specialists recommend
intensified therapy when CNS syphilis is suspected in these
persons. Therefore, some specialists recommend CSF examination
before treatment of HIV-infected persons with early syphilis,
with follow-up CSF examination conducted after treatment in
persons with initial abnormalities.
Follow-Up.
HIV-infected persons should be evaluated clinically and serologically
for treatment failure at 3, 6, 9, 12, and 24 months after
therapy. Although of unproven benefit, some specialists recommend
a CSF examination 6 months after therapy.
HIV-infected
persons who meet the criteria for treatment failure (i.e.,
signs or symptoms that persist or recur or persons who have
fourfold increase in nontreponemal test titer) should be managed
in the same manner as HIV-negative patients (i.e., a CSF examination
and re-treatment). CSF examination and re-treatment also should
be strongly considered for persons whose nontreponemal test
titers do not decrease fourfold within 6--12 months of therapy.
The majority of specialists would re-treat patients with benzathine
penicillin G administered as 3 doses of 2.4 million units
IM each at weekly intervals, if CSF examinations are normal.
Special
Considerations
Penicillin
Allergy. Penicillin-allergic patients who have primary or
secondary syphilis and HIV infection should be managed according
to the recommendations for penicillin-allergic, HIV-negative
patients. The use of alternatives to penicillin has not been
well studied in HIV-infected patients.
Latent
Syphilis Among HIV-Infected Persons
Diagnostic
Considerations
HIV-infected
patients who have early latent syphilis should be managed
and treated according to the recommendations for HIV-negative
patients who have primary and secondary syphilis. HIV-infected
patients who have either late latent syphilis or syphilis
of unknown duration should have a CSF examination before treatment.
Treatment
Patients
with late latent syphilis or syphilis of unknown duration
and a normal CSF examination can be treated with benzathine
penicillin G, at weekly doses of 2.4 million units for 3 weeks.
Patients who have CSF consistent with neurosyphilis should
be treated and managed as patients who have neurosyphilis
(see Neurosyphilis).
Follow-Up
Patients
should be evaluated clinically and serologically at 6, 12,
18, and 24 months after therapy. If, at any time, clinical
symptoms develop or nontreponemal titers rise fourfold, a
repeat CSF examination should be performed and treatment administered
accordingly. If during 12--24 months the nontreponemal titer
does not decline fourfold, the CSF examination should be repeated
and treatment administered accordingly.
Special
Considerations
Penicillin
Allergy. The efficacy of alternative nonpenicillin regimens
in HIV-infected persons has not been well studied. Patients
with penicillin allergy whose compliance with therapy or follow-up
cannot be ensured should be desensitized and treated with
penicillin (see Management of Patients Who Have a History
of Penicillin Allergy). These therapies should be used only
in conjunction with close serologic and clinical follow-up.
Limited clinical studies, along with biologic and pharmacologic
evidence, suggest that ceftriaxone might be effective. However,
optimal dose and duration of ceftriaxone therapy have not
been defined.
Syphilis
During Pregnancy
All
women should be screened serologiclly for syphilis during
the early stages of pregnancy. The majority of states mandate
screening at the first prenatal visit for all women. Antepartum
screening by nontreponemal antibody testing is typical, but
in some settings, treponemal antibody testing is being used.
Pregnant women with reactive treponemal screening tests should
have confirmatory testing with nontreponemal tests with titers.
In populations in which use of prenatal care is not optimal,
RPR-card test screening and treatment (i.e., if the RPR-card
test is reactive) should be performed at the time a pregnancy
is diagnosed. For communities and populations in which the
prevalence of syphilis is high or for patients at high risk,
serologic testing should be performed twice during the third
trimester, at 28 to 32 weeks' gestation and at delivery. Any
woman who delivers a stillborn infant after 20 weeks' gestation
should be tested for syphilis. No infant should leave the
hospital without the maternal serologic status having been
determined at least once during pregnancy.
Diagnostic
Considerations
Seropositive
pregnant women should be considered infected unless an adequate
treatment history is documented clearly in the medical records
and sequential serologic antibody titers have declined. Serofast
low antibody titers might not require treatment; however,
persistent higher titer antibody tests might indicate reinfection
and require treatment.
Treatment
Penicillin
is effective for preventing maternal transmission to the fetus
and for treating fetal infection. Evidence is insufficient
to determine specific, recommended penicillin regimens that
are optimal (107).
Recommended
Regimen
Treatment during pregnancy should be the penicillin regimen
appropriate for the stage of syphilis.
Other
Management Considerations
Some
specialists recommend additional therapy for pregnant women
in some settings (e.g., a second dose of benzathine penicillin
2.4 million units IM administered 1 week after the initial
dose for women who have primary, secondary, or early latent
syphilis). During the second half of pregnancy, syphilis management
may be facilitated by a sonographic fetal evaluation for congenital
syphilis, but this evaluation should not delay therapy. Sonographic
signs of fetal or placental syphilis (i.e., hepatomegaly,
ascites, hydrops, or a thickened placenta) indicate a greater
risk for fetal treatment failure; such cases should be managed
in consultation with obstetric specialists. Evidence is insufficient
to recommend specific regimens for these situations.
Women
treated for syphilis during the second half of pregnancy are
at risk for premature labor and/or fetal distress, if the
treatment precipitates the Jarisch-Herxheimer reaction. These
women should be advised to seek obstetric attention after
treatment, if they notice any contractions or decrease in
fetal movements. Stillbirth is a rare complication of treatment,
but concern for this complication should not delay necessary
treatment. All patients who have syphilis should be offered
testing for HIV infection.
Follow-Up.
Coordinated prenatal care and treatment follow-up are vital.
Serologic titers should be repeated at 28--32 weeks' gestation,
at delivery, and following the recommendations for the stage
of disease. Serologic titers can be checked monthly in women
at high risk for reinfection or in geographic areas in which
the prevalence of syphilis is high. The clinical and antibody
response should be appropriate for the stage of disease. The
majority of women will deliver before their serologic response
to treatment can be assessed definitively. Inadequate maternal
treatment is likely if delivery occurs within 30 days of therapy,
if clinical signs of infection are present at delivery, or
if the maternal antibody titer is fourfold higher than the
pretreatment titer.
Management
of Sex Partners. See General Principles, Management of Sex
Partners.
Special
Considerations
Penicillin
Allergy. For treatment of syphilis during pregnancy, no proven
alternatives to penicillin exist. Pregnant women who have
a history of penicillin allergy should be desensitized and
treated with penicillin. Skin testing might be helpful (see
Management of Patients Who Have a History of Penicillin Allergy).
Tetracycline
and doxycycline usually are not used during pregnancy. Erythromycin
should not be used because it does not reliably cure an infected
fetus. Data are insufficient to recommend azithromycin or
ceftriaxone for treatment of maternal infection and prevention
of congenital syphilis.
HIV Infection. Placental inflammation from congenital infection
might increase the risk for perinatal transmission of HIV.
All HIV-infected women should be evaluated for infectious
syphilis and treated. Data are insufficient to recommend a
specific regimen (see Syphilis Among HIV-Infected Patients).
Effective
prevention and detection of congenital syphilis depends on
the identification of syphilis in pregnant women and, therefore,
on the routine serologic screening of pregnant women during
the first prenatal visit. In communities and populations in
which the risk for congenital syphilis is high, serologic
testing and a sexual history also should be obtained at 28
weeks' gestation and at delivery. Moreover, as part of the
management of pregnant women who have syphilis, information
concerning treatment of sex partners should be obtained to
assess the risk for reinfection. All pregnant women who have
syphilis should be tested for HIV infection. Routine screening
of newborn sera or umbilical cord blood is not recommended.
Serologic testing of the mother's serum is preferred rather
than testing of the infant's serum because the serologic tests
performed on infant serum can be nonreactive if the mother's
serologic test result is of low titer or was infected late
in pregnancy (see Diagnostic Considerations and Use of Serologic
Tests). No infant or mother should leave the hospital unless
the maternal serologic status has been documented at least
once during pregnancy, and at delivery in communities and
populations in which the risk for congenital syphilis is high.
Evaluation
and Treatment of Infants During the First Month of Life
The
diagnosis of congenital syphilis is complicated by the transplacental
transfer of maternal nontreponemal and treponemal IgG antibodies
to the fetus. This transfer of antibodies makes the interpretation
of reactive serologic tests for syphilis in infants difficult.
Treatment decisions frequently must be made on the basis of
1) identification of syphilis in the mother;
2) adequacy of maternal treatment;
3) presence of clinical, laboratory, or radiographic evidence
of syphilis in the infant; and
4) comparison of maternal (at delivery) and infant nontreponemal
serologic titers by using the same test and preferably the
same laboratory.
All
infants born to mothers who have reactive nontreponemal and
treponemal test results should be evaluated with a quantitative
nontreponemal serologic test (RPR or VDRL) performed on infant
serum because umbilical cord blood can become contaminated
with maternal blood and could yield a false-positive result.
Conducting a treponemal test (i.e., TP-PA or FTA-ABS) on a
newborn's serum is not necessary. No commercially available
immunoglobulin (IgM) test can be recommended.
All
infants born to women who have reactive serologic tests for
syphilis should be examined thoroughly for evidence of congenital
syphilis (e.g., nonimmune hydrops, jaundice, hepatosplenomegaly,
rhinitis, skin rash, and/or pseudoparalysis of an extremity).
Pathologic examination of the placenta or umbilical cord by
using specific fluorescent antitreponemal antibody staining
is suggested. Darkfield microscopic examination or DFA staining
of suspicious lesions or body fluids (e.g., nasal discharge)
also should be performed.
The
following scenarios describe the evaluation and treatment
of infants for congenital syphilis:
Scenario
1. Infants with proven or highly probable disease and
1. an abnormal physical examination that is consistent with
congenital syphilis,
2. a serum quantitative nontreponemal serologic titer that
is fourfold higher than the mother's titer,§ or
3. a positive darkfield or fluorescent antibody test of body
fluid(s).
Recommended
Evaluation
-
CSF analysis for VDRL, cell count, and protein
- Complete
blood count (CBC) and differential and platelet count
- Other
tests as clinically indicated (e.g., long-bone radiographs,
chest radiograph, liver-function tests, cranial ultrasound,
ophthalmologic examination, and auditory brainstem response)
Recommended
Regimens
Aqueous crystalline penicillin G 100,000--150,000 units/kg/day,
administered as 50,000 units/kg/dose IV every 12 hours during
the first 7 days of life and every 8 hours thereafter for
a total of 10 days OR
Procaine penicillin G 50,000 units/kg/dose IM in a single
daily dose for 10 days
If
>1 day of therapy is missed, the entire course should be
restarted. Data are insufficient regarding the use of other
antimicrobial agents (e.g., ampicillin). When possible, a
full 10-day course of penicillin is preferred, even if ampicillin
was initially provided for possible sepsis. The use of agents
other than penicillin requires close serologic follow-up to
assess adequacy of therapy. In all other situations, the maternal
history of infection with T. pallidum and treatment for syphilis
must be considered when evaluating and treating the infant.
Scenario
2. Infants who have a normal physical examination and a serum
quantitive nontreponemal serologic titer the same or less
than fourfold the maternal titer and the
1. mother was not treated, inadequately treated, or has no
documentation of having received treatment;
2. mother was treated with erythromycin or other nonpenicillin
regimen;** or
3. mother received treatment <4 weeks before delivery.
Recommended
Evaluation
-
CSF analysis for VDRL, cell count, and protein
- CBC
and differential and platelet count
- Long-bone
radiographs
A
complete evaluation is not necessary if 10 days of parenteral
therapy is administered. However, such evaluations might be
useful; a lumbar puncture might document CSF abnormalities
that would prompt close follow-up. Other tests (e.g., CBC,
platelet count, and bone radiographs) may be performed to
further support a diagnosis of congenital syphilis. If a single
dose of benzathine penicillin G is used, then the infant must
be fully evaluated (i.e., through CSF examination, long-bone
radiographs, and CBC with platelets), the full evaluation
must be normal, and follow-up must be certain. If any part
of the infant's evaluation is abnormal or not performed or
if the CSF analysis is rendered uninterpretable because of
contamination with blood, then a 10-day course of penicillin
is required.
Recommended
Regimens
Aqueous crystalline penicillin G 100,000--150,000 units/kg/day,
administered as 50,000 units/kg/dose IV every 12 hours during
the first 7 days of life and every 8 hours thereafter for
a total of 10 days
OR
Procaine penicillin G 50,000 units/kg/dose IM in a single
daily dose for 10 days
OR
Benzathine penicillin G 50,000 units/kg/dose IM in a single
dose
Some
specialists prefer the 10 days of parenteral therapy if the
mother has untreated early syphilis at delivery.
Scenario 3. Infants who have a normal physical examination
and a serum quantitative nontreponemal serologic titer the
same or less than fourfold the maternal titer and the
-
mother was treated during pregnancy, treatment was appropriate
for the stage of infection, and treatment was administered
>4 weeks before delivery; and
-
mother has no evidence of reinfection or relapse.
Recommended
Evaluation
No
evaluation is required.
Recommended
Regimen
Benzathine penicillin G 50,000 units/kg/dose IM in a single
dose§§
Scenario
4. Infants who have a normal physical examination and a serum
quantitative nontreponemal serologic titer the same or less
than fourfold the maternal titer and the
1. mother's treatment was adequate before pregnancy, and
2. mother's nontreponemal serologic titer remained low and
stable before and during pregnancy and at delivery (VDRL <1:2;
RPR <1:4).
Recommended
Evaluation
No
evaluation is required.
Recommended
Regimen
No treatment is required; however, some specialists would
treat with benzathine penicillin G 50,000 units/kg as a single
IM injection, particularly if follow-up is uncertain.
Evaluation and Treatment of Older Infants and Children
Children
who are identified as having reactive serologic tests for
syphilis after the neonatal period (i.e., aged >1 month)
should have maternal serology and records reviewed to assess
whether the child has congenital or acquired syphilis (see
Primary and Secondary Syphilis and Latent Syphilis, Sexual
Assault or Abuse of Children). Any child at risk for congenital
syphilis should receive a full evaluation and testing for
HIV infection.
Recommended
Evaluation
-
CSF analysis for VDRL, cell count, and protein
- CBC,
differential, and platelet count
- Other
tests as clinically indicated (e.g., long-bone radiographs,
chest radiograph, liver function tests, abdominal ultrasound,
ophthalmologic examination, and auditory brain stem response)
Recommended
Regimen
Aqueous crystalline penicillin G 200,000--300,000 units/kg/day
IV, administered as 50,000 units/kg every 4--6 hours for 10
days
If
the child has no clinical manifestations of disease, the CSF
examination is normal, and the CSF VDRL test result is negative,
some specialists would treat with up to 3 weekly doses of
benzathine penicillin G, 50,000 U/kg IM.
Any
child who is suspected of having congenital syphilis or who
has neurologic involvement should be treated with aqueous
penicillin G. Some specialists also suggest giving these patients
a single dose of benzathine penicillin G, 50,000 units/kg
IM after the 10-day course of IV aqueous penicillin. This
treatment also would be adequate for children who might have
other treponemal infections.
Follow-Up
All
seroreactive infants (or infants whose mothers were seroreactive
at delivery) should receive careful follow-up examinations
and serologic testing (i.e., a nontreponemal test) every 2--3
months until the test becomes nonreactive or the titer has
decreased fourfold. Nontreponemal antibody titers should decline
by age 3 months and should be nonreactive by age 6 months
if the infant was not infected (i.e., if the reactive test
result was caused by passive transfer of maternal IgG antibody)
or was infected but adequately treated. The serologic response
after therapy might be slower for infants treated after the
neonatal period. If these titers are stable or increase after
age 6--12 months, the child should be evaluated (e.g., given
a CSF examination) and treated with a 10-day course of parenteral
penicillin G.
Treponemal
tests should not be used to evaluate treatment response because
the results for an infected child can remain positive despite
effective therapy. Passively transferred maternal treponemal
antibodies can be present in an infant until age 15 months.
A reactive treponemal test after age 18 months is diagnostic
of congenital syphilis. If the nontreponemal test is nonreactive
at this time, no further evaluation or treatment is necessary.
If the nontreponemal test is reactive at age 18 months, the
infant should be fully (re)evaluated and treated for congenital
syphilis.
Infants
whose initial CSF evaluations are abnormal should undergo
a repeat lumbar puncture approximately every 6 months until
the results are normal. A reactive CSF VDRL test or abnormal
CSF indices that cannot be attributed to other ongoing illness
requires re-treatment for possible neurosyphilis.
Follow-up
of children treated for congenital syphilis after the newborn
period should be conducted as is recommended for neonates.
Special
Considerations
Penicillin
Allergy
Infants
and children who require treatment for syphilis but who have
a history of penicillin allergy or develop an allergic reaction
presumed secondary to penicillin should be desensitized, if
necessary, and then treated with penicillin (see Management
of Patients With a History of Penicillin Allergy). Data are
insufficient regarding the use of other antimicrobial agents
(e.g., ceftriaxone); if a nonpenicillin agent is used, close
serologic and CSF follow-up are indicated.
HIV
Infection
Evidence
is insufficient to determine whether infants who have congenital
syphilis and whose mothers are coinfected with HIV require
different evaluation, therapy, or follow-up for syphilis than
is recommended for all infants.
Penicillin
Shortage
During
periods when the availability of penicillin is compromised,
the following is recommended (see http://www.cdc.gov/nchstp/dstd/penicillinG.htm):
-
For infants with clinical evidence of congenital syphilis
(Scenario 1), check local sources for aqueous crystalline
penicillin G (potassium or sodium). If IV penicillin G is
limited, substitute some or all daily doses with procaine
penicillin G (50,000 U/kg/dose IM a day in a single daily
dose for 10 days).
If
aqueous or procaine penicillin G is not available, ceftriaxone
(in doses according to age and weight) may be considered
with careful clinical and serologic follow-up. Ceftriaxone
must be used with caution in infants with jaundice. For
infants aged >30 days, use 75 mg/kg IV/IM a day in a
single daily dose for 10--14 days; however, dose adjustment
might be necessary based on birthweight. For older infants,
the dose should be 100 mg/kg a day in a single daily dose.
Studies that strongly support ceftriaxone for the treatment
of congenital syphilis have not been conducted. Therefore,
ceftriaxone should be used in consultation with a specialist
in the treatment of infants with congenital syphilis. Management
may include a repeat CSF examination at age 6 months if
the initial examination was abnormal.
-
For infants at risk for congenital syphilis without any
clinical evidence of infection (Scenarios 2 and 3), use
a. procaine penicillin G, 50,000 U/kg/dose IM a day in a
single dose for 10 days;
OR
b. benzathine penicillin G, 50,000 U/kg IM as a single dose.
If any part of the evaluation for congenital syphilis is
abnormal, CSF examination is not interpretable, CSF examination
was not performed, or follow-up is uncertain, Procaine penicillin
G is recommended. A single dose of ceftriaxone is inadequate
therapy.
- For
premature infants at risk for congenital syphilis but who
have no other clinical evidence of infection (Scenarios
2 and 3) and who might not tolerate IM injections because
of decreased muscle
mass, IV ceftriaxone may be considered with careful clinical
and serologic follow-up (see Penicillin Shortage, Number
1). Ceftriaxone dosing must be adjusted to age and birthweight.
|
Management
of Patients Who Have a History of Penicillin Allergy
|
No
proven alternatives to penicillin are available for treating
neurosyphilis, congenital syphilis, or syphilis in pregnant
women. Penicillin also is recommended for use, whenever possible,
in HIV-infected patients. Of the adult U.S. population, 3%--10%
have experienced an immunoglobulin E (IgE) mediated allergic
response to penicillin such as urticaria, angioedema, or anaphylaxis
(i.e., upper airway obstruction, bronchospasm, or hypotension).
Re-administration of penicillin to these patients can cause
severe, immediate reactions. Because anaphylactic reactions
to penicillin can be fatal, every effort should be made to
avoid administering penicillin to penicillin-allergic patients,
unless they undergo acute desensitization to eliminate anaphylactic
sensitivity.
An
estimated 10% of persons who report a history of severe allergic
reactions to penicillin remain allergic. With the passage
of time, the majority of persons who have had a severe reaction
to penicillin stop expressing penicillin-specific IgE. These
persons can be treated safely with penicillin. The results
of many investigations indicate that skin testing with the
major and minor determinants of penicillin can reliably identify
persons at high risk for penicillin reactions. Although these
reagents are easily generated and have been available for
>30 years, only benzylpenicilloyl poly-L-lysine (Pre-Pen®
[i.e., the major determinant]) and penicillin G have been
available commercially. Testing with only the major determinant
and penicillin G identifies an estimated 90%--97% of the currently
allergic patients. However, because skin testing without the
minor determinants would still miss 3%--10% of allergic patients
and because serious or fatal reactions can occur among these
minor-determinant--positive patients, specialists suggest
exercising caution when the full battery of skin-test reagents
is not available (Box
1). An additional challenge has occurred with the recent
unavailability of Pre-Pen®; however, plans for future
availability of this product have been made, as well as a
companion minor determinant mixture.
Recommendations
If
the full battery of skin-test reagents is available, including
the major and minor determinants (see Penicillin Allergy Skin
Testing), patients who report a history of penicillin reaction
and who are skin-test negative can receive conventional penicillin
therapy. Skin-test--positive patients should be desensitized.
If
the full battery of skin-test reagents, including the minor
determinants, is not available, the patient should be skin
tested using benzylpenicilloyl poly-L-lysine (i.e., the major
determinant) and penicillin G. Patients who have positive
test results should be desensitized. Some specialists suggest
that persons who have negative test results should be regarded
as probably allergic and should be desensitized. Others suggest
that those with negative skin-test results can be test-dosed
gradually with oral penicillin in a monitored setting in which
treatment for anaphylactic reaction can be provided.
If
the major determinant (Pre-Pen®) is not available for
skin testing, all patients with a history suggesting IgE mediated
reactions (anaphylaxis, angioedema, bronchospasm, or urticaria)
to penicillin should be desensitized in a hospital setting.
In patients with reactions not likely to be IgE mediated,
outpatient oral desensitization or monitored test doses may
be considered.
Penicillin
Allergy Skin Testing
Patients
at high risk for anaphylaxis, including those who 1) have
a history of penicillin-related anaphylaxis, asthma, or other
diseases that would make anaphylaxis more dangerous or 2)
are being treated with beta-adrenergic blocking agents should
be tested with 100-fold dilutions of the full-strength skin-test
reagents before being tested with full-strength reagents.
In these situations, patients should be tested in a monitored
setting in which treatment for an anaphylactic reaction is
available. If possible, the patient should not have taken
antihistamines recently (e.g., chlorpheniramine maleate or
terfenadine during the preceding 24 hours, diphenhydramine
HCl or hydroxyzine during the preceding 4 days, or astemizole
during the preceding 3 weeks).
Procedures
Dilute
the antigens either 1) 100-fold for preliminary testing if
the patient has had a life-threatening reaction to penicillin
or 2) 10-fold if the patient has had another type of immediate,
generalized reaction to penicillin within the preceding year.
Epicutaneous
(Prick) Tests
Duplicate
drops of skin-test reagent are placed on the volar surface
of the forearm. The underlying epidermis is pierced with a
26-gauge needle without drawing blood.
An
epicutaneous test is positive if the average wheal diameter
after 15 minutes is 4 mm larger than that of negative controls;
otherwise, the test is negative. The histamine controls should
be positive to ensure that results are not falsely negative
because of the effect of antihistaminic drugs.
Intradermal
Test
If
epicutaneous tests are negative, duplicate 0.02-mL intradermal
injections of negative control and antigen solutions are made
into the volar surface of the forearm by using a 26- or 27-gauge
needle on a syringe. The diameters of the wheals induced by
the injections should be recorded.
An intradermal test is positive if the average wheal diameter
15 minutes after injection is >2 mm larger than the initial
wheal size and also is >2 mm larger than the negative controls.
Otherwise, the tests are negative.
Desensitization
Patients
who have a positive skin test to one of the penicillin determinants
can be desensitized (Table 1). This is a straightforward,
relatively safe procedure that can be performed orally or
IV. Although the two approaches have not been compared, oral
desensitization is regarded as safer and easier to perform.
Patients should be desensitized in a hospital setting because
serious IgE-mediated allergic reactions can occur. Desensitization
usually can be completed in approximately 4 hours, after which
the first dose of penicillin is administered. After desensitization,
patients must be maintained on penicillin continuously for
the duration of the course of therapy.
|
Diseases
Characterized by Urethritis and Cervicitis
|
Management
of Male Patients Who Have Urethritis
Urethritis,
as characterized by urethral inflammation, can result from
infectious and noninfectious conditions. Symptoms, if present,
include discharge of mucopurulent or purulent material, dysuria,
or urethral pruritis. Asymptomatic infections are common.
N. gonorrhoeae and C. trachomatis are clinically important
infectious causes of urethritis. If clinic-based diagnostic
tools (Gram stain microscopy) are not available, patients
should be treated for both gonorrhea and chlamydia. Further
testing to determine the specific etiology is recommended
because both chlamydia and gonorrhea are reportable to state
health departments, and a specific diagnosis might enhance
partner notification and improve compliance with treatment,
especially in exposed partners. Culture, nucleic acid hybridization
tests, and nucleic acid amplification tests are available
for the detection of both N. gonorrhoeae and C. trachomatis.
Culture and hybridization tests require urethral swab specimens,
whereas amplification tests can be performed on urine specimens.
Because of their higher sensitivity, amplification tests are
preferred for the detection of C. trachomatis.
Etiology
Several
organisms can cause infectious urethritis. The presence of
Gram-negative intracellular diplococci (GNID) on urethral
smear is indicative of gonorrhea infection, which is frequently
accompanied by chlamydial infection. Nongonoccocal urethritis
(NGU) is diagnosed when microscopy indicates inflammation
without GNID. C. trachomatis is a frequent cause of NGU (i.e.,
15%--55% of cases); however, the prevalence varies by age
group, with lower prevalence among older men. The proportion
of NGU cases caused by chlamydia has been declining gradually.
Complications of NGU among men infected with C. trachomatis
include epididymitis, prostatitis, and Reiter's syndrome.
Documentation of chlamydia infection is essential because
of the need for partner referral for evaluation and treatment.
The
etiology of the majority of cases of nonchlamydial NGU is
unknown. Ureaplasma urealyticum and Mycoplasma genitalium
have been implicated as etiologic agents of NGU in some studies;
however, detection of these organisms is frequently difficult.
T. vaginalis, HSV, and adenovirus might also cause NGU. Diagnostic
and treatment procedures for these organisms are reserved
for situations in which these infections are suspected (e.g.,
contact with trichomoniasis and genital lesions or severe
dysuria and meatitis, which might suggest genital herpes)
or when NGU is not responsive to therapy. Enteric bacteria
have been identified as an uncommon cause of NGU and might
be associated with insertive anal sex.
Confirmed
Urethritis
Clinicians
should document that urethritis is present. Urethritis can
be documented on the basis of any of the following signs or
laboratory tests:
- Mucopurulent
or purulent discharge.
- Gram
stain of urethral secretions demonstrating >5 WBC per
oil immersion field. The Gram stain is the preferred rapid
diagnostic test for evaluating urethritis. It is highly
sensitive and specific for documenting both urethritis and
the presence or absence of gonococcal infection. Gonococcal
infection is established by documenting the presence of
WBC containing GNID, or
- Positive
leukocyte esterase test on first-void urine or microscopic
examination of first-void urine sediment demonstrating >10
WBC per high power field.
If
none of these criteria are present, treatment should be deferred,
and the patient should be tested for N. gonorrhoeae and C.
trachomatis and followed closely if test results are negative.
If the results demonstrate infection with either N. gonorrhoeae
or C. trachomatis, the appropriate treatment should be given
and sex partners referred for evaluation and treatment.
Empiric
treatment of symptoms without documentation of urethritis
is recommended only for patients at high risk for infection
who are unlikely to return for a follow-up evaluation. Such
patients should be treated for gonorrhea and chlamydia. Partners
of patients treated empirically should be evaluated and treated.
Management
of Patients Who Have Nongonococcal Urethritis
Diagnosis
All
patients who have confirmed or suspected urethritis should
be tested for gonorrhea and chlamydia. Testing for chlamydia
is strongly recommended because of the increased utility and
availability of highly sensitive and specific testing methods
and because a specific diagnosis might enhance partner notification
and improve compliance with treatment, especially in the exposed
partner.
Treatment
Treatment
should be initiated as soon as possible after diagnosis. Azithromycin
and doxycycline are highly effective for chlamydial urethritis;
however, infections with M. genitalium may respond better
to azithromycin. Single-dose regimens have the advantage of
improved compliance and directly observed treatment. To improve
compliance, ideally the medication should be provided in the
clinic or health-care provider's office.
Recommended
Regimens
Azithromycin 1 g orally in a single dose
OR
Doxycycline 100 mg orally twice a day for 7 days
Alternative Regimens
Erythromycin base 500 mg orally four times a day for 7 days
OR
Erythromycin ethylsuccinate 800 mg orally four times a day
for 7 days
OR
Ofloxacin 300 mg orally twice a day for 7 days
OR
Levofloxacin 500 mg orally once daily for 7 days
Follow-Up
for Patients Who Have Urethritis
Patients
should be instructed to return for evaluation if symptoms
persist or recur after completion of therapy. Symptoms alone,
without documentation of signs or laboratory evidence of urethral
inflammation, are not a sufficient basis for re-treatment.
Patients should be instructed to abstain from sexual intercourse
until 7 days after therapy is initiated, provided their symptoms
have resolved and their sex partners have been adequately
treated. Persistence of pain, discomfort, and irritative voiding
symptoms beyond 3 months should alert the clinician to the
possibility of chronic prostatitis/chronic pelvic pain syndrome
in men. Persons whose conditions have been diagnosed as a
new STD should receive testing for other STDs, including syphilis
and HIV.
Partner
Referral
Persons
with NGU should refer for evaluation and treatment all sex
partners within the preceding 60 days. Because a specific
diagnosis might facilitate partner referral, testing for gonorrhea
and chlamydia is encouraged.
Recurrent
and Persistent Urethritis
Objective
signs of urethritis should be present before initiation of
antimicrobial therapy. In persons who have persistent symptoms
after treatment without objective signs of urethritis, the
value of extending the duration of antimicrobials has not
been demonstrated. Persons who have persistent or recurrent
urethritis can be re-treated with the initial regimen if they
did not comply with the treatment regimen or if they were
reexposed to an untreated sex partner. Otherwise, a T. vaginalis
culture should be performed using an intraurethral swab or
a first-void urine specimen. Some cases of recurrent urethritis
after doxycycline treatment might be caused by tetracycline-resistant
U. urealyticum. Urologic examinations usually do not reveal
a specific etiology. Approximately 50% of men with chronic
nonbacterial prostatitis/chronic pelvic pain syndrome have
evidence of urethral inflammation without any identifiable
microbial pathogens. If the patient was compliant with the
initial regimen and reexposure can be excluded, the following
regimen is recommended.
Recommended
Regimens
Metronidazole 2 g orally in a single dose
OR
Tinidazole 2 g orally in a single dose
PLUS
Azithromycin 1 g orally in a single dose (if not used for
initial episode)
Special
Considerations
HIV
Infection
Gonococcal
urethritis, chlamydial urethritis, and nongonococcal, nonchlamydial
urethritis might facilitate HIV transmission. Patients who
have NGU and also are infected with HIV should receive the
same treatment regimen as those who are HIV negative.
Management
of Patients Who Have Cervicitis
Two
major diagnostic signs characterize cervicitis: 1) a purulent
or mucopurulent endocervical exudate visible in the endocervical
canal or on an endocervical swab specimen (commonly referred
to as "mucopurulent cervicitis" or cervicitis),
and 2) sustained endocervical bleeding easily induced by gentle
passage of a cotton swab through the cervical os. Either or
both signs might be present. Cervicitis frequently is asymptomatic,
but some women complain of an abnormal vaginal discharge and
intermenstrual vaginal bleeding (e.g., after sexual intercourse).
A finding of leukorrhea (>10 WBC per high power field on
microscopic examination of vaginal fluid) has been associated
with chlamydial and gonococcal infection of the cervix. In
the absence of inflammatory vaginitis, leukorrhea might be
a sensitive indicator of cervical inflammation with a high
negative predictive value. Although some specialists consider
an increased number of polymorphonuclear leukocytes on endocervical
Gram stain as being useful in the diagnosis of cervicitis,
this criterion has not been standardized. In addition, it
has a low positive-predictive value (PPV) for infection with
C. trachomatis and N. gonorrhoeae and is not available in
the majority of clinical settings. Finally, although the presence
of GNID on Gram stain of endocervical fluid is specific for
the diagnosis of gonococcal cervical infection, it is insensitive
because it is observed in only 50% of women with this infection.
Etiology
When
an etiologic organism is isolated in the setting of cervicitis,
it is typically C. trachomatis or N. gonorrhoeae. Cervicitis
also can accompany trichomoniasis and genital herpes (especially
primary HSV-2 infection). However, in the majority of cases
of cervicitis, no organism is isolated, especially in women
at relatively low risk for recent acquisition of these STDs
(for example, women aged >30 years). Limited data indicate
that infection with M. genitalium and BV as well as frequent
douching might cause cervicitis. For reasons that are unclear,
cervicitis can persist despite repeated courses of antimicrobial
therapy. Because the majority of persistent cases of cervicitis
are not caused by relapse or reinfection with C. trachomatis
or N. gonorrhoeae, other determinants (e.g., persistent abnormality
of vaginal flora, douching or exposure to chemical irritants,
or idiopathic inflammation in the zone of ectopy) might be
involved.
Diagnosis
Because
cervicitis might be a sign of upper genital tract infection
(endometritis), women who seek medical treatment for a new
episode of cervicitis should be assessed for signs of PID
and should be tested for C. trachomatis and for N. gonorrhoeae
with the most sensitive and specific test available, NAAT.
Women with cervicitis also should be evaluated for the presence
of BV and trichomoniasis, and these conditions should be treated,
if present. Because the sensitivity of microscopy to detect
T. vaginalis is relatively low (approximately 50%), symptomatic
women with cervicitis and negative microscopy for trichomonads
should receive further testing (i.e., culture or antigen-based
detection). Although HSV-2 infection has been associated with
cervicitis, the utility of specific testing (i.e., culture
or serologic testing) for HSV-2 in this setting is unclear.
Standardized diagnostic tests for M. genitalium are not commercially
available.
NAAT
for C. trachomatis and N. gonorrhoeae are preferred for the
diagnostic evaluation of cervicitis and can be performed on
either cervical or urine samples. A finding of >10 WBC
in vaginal fluid, in the absence of trichomoniasis, might
indicate endocervical inflammation caused specifically by
C. trachomatis or N. gonorrhoeae.
Treatment
Several
factors should affect the decision to provide presumptive
therapy for cervicitis or to await the results of diagnostic
tests. Treatment with antibiotics for C. trachomatis should
be provided in women at increased risk for this common STD
(age <25 years, new or multiple sex partners, and unprotected
sex), especially if follow-up cannot be ensured and if a relatively
insensitive diagnostic test (not a NAAT) is used. Concurrent
therapy for N. gonorrhoeae is indicated if the prevalence
of this infection is high (>5%) in the patient population
(young age and facility prevalence).
Concomitant
trichomoniasis or symptomatic BV should also be treated if
detected. For women in whom any component of (or all) presumptive
therapy is deferred, the results of sensitive tests for C.
trachomatis and N. gonorrhoeae (e.g., nucleic acid amplification
tests) should determine the need for treatment subsequent
to the initial evaluation.
Recommended
Regimens for Presumptive Treatment*
Azithromycin 1 g orally in a single dose
OR
Doxycycline 100 mg orally twice a day for 7 days
* Consider concurrent treatment for gonococcal infection
if prevalence of gonorrhea is high in the patient population
under assessment.
Recurrent
and Persistent Cervicitis
Women
with persistent cervicitis should be reevaluated for possible
reexposure to an STD, and her vaginal flora should be reassessed.
If relapse and/or reinfection with a specific STD has been
excluded, BV is not present, and sex partners have been evaluated
and treated, management options for persistent cervicitis
are undefined. For such women, the value of repeated or prolonged
administration of antibiotic therapy for persistent symptomatic
cervicitis is unknown. Women who receive such a course should
return after treatment so that a determination can be made
regarding whether cervicitis has resolved. In women with persistent
symptoms that are clearly attributable to cervicitis, ablative
therapy may be considered by a gynecologic specialist.
Follow-Up
Follow-up
should be conducted as recommended for the infections for
which a woman is treated. If symptoms persist, women should
be instructed to return for reevaluation.
Management
of Sex Partners
Management
of sex partners of women treated for cervicitis should be
appropriate for the identified or suspected STD. Partners
should be notified and examined if chlamydia, gonorrhea, or
trichomoniasis was identified or suspected in the index patient
and treated for the STDs for which the index patient received
treatment. To avoid re-infection, patients and their sex partners
should abstain from sexual intercourse until therapy is completed
(i.e., 7 days after a single-dose regimen or after completion
of a 7-day regimen).
Special
Considerations
HIV
Infection
Patients
who have cervicitis and also are infected with HIV should
receive the same treatment regimen as those who are HIV negative.
Treatment of cervicitis in HIV-infected women is vital because
cervicitis increases cervical HIV shedding. Treatment of cervicitis
in HIV-infected women reduces HIV shedding from the cervix
and might reduce HIV transmission to susceptible sex partners.
Chlamydial
Infections
Chlamydial
Infections in Adolescents and Adults
In
the United States, chlamydial genital infection is the most
frequently reported infectious disease, and the prevalence
is highest in persons aged <25 years. Several important
sequelae can result from C. trachomatis infection in women;
the most serious of these include PID, ectopic pregnancy,
and infertility. Some women who have uncomplicated cervical
infection already have subclinical upper reproductive tract
infection.
Asymptomatic
infection is common among both men and women, and to detect
chlamydial infections health-care providers frequently rely
on screening tests. Annual screening of all sexually active
women aged <25 years is recommended, as is screening of
older women with risk factors (e.g., those who have a new
sex partner or multiple sex partners). The benefits of C.
trachomatis screening in women have been demonstrated in areas
where screening programs have reduced both the prevalence
of infection and rates of PID. Evidence is insufficient to
recommend routine screening for C. trachomatis in sexually
active young men, based on feasibility, efficacy, and cost-effectiveness.
However, screening of sexually active young men should be
considered in clinical settings with a high prevalence of
chlamydia (e.g., adolescent clinics, correctional facilities,
and STD clinics). An appropriate sexual risk assessment should
be conducted for all persons and might indicate more frequent
screening for some women or certain men.
Diagnostic
Considerations
C.
trachomatis urogenital infection in women can be diagnosed
by testing urine or swab specimens collected from the endocervix
or vagina. Diagnosis of C. trachomatis urethral infection
in men can be made by testing a urethral swab or urine specimen.
Rectal C. trachomatis infections in persons that engage in
receptive anal intercourse can be diagnosed by testing a rectal
swab specimen. Culture, direct immunofluorescence, EIA, nucleic
acid hybridization tests, and NAATs are available for the
detection of C. trachomatis on endocervical and male urethral
swab specimens. NAATs are the most sensitive tests for these
specimens and are FDA-cleared for use with urine, and some
tests are cleared for use with vaginal swab specimens. The
majority of tests, including NAAT and nucleic acid hybridization
tests, are not FDA-cleared for use with rectal swab specimens,
and chlamydia culture is not widely available for this purpose.
Some noncommercial laboratories have initiated NAAT of rectal
swab specimens after establishing the performance of the test
to meet CLIA requirements. Patients' whose condition has been
diagnosed as chlamydia also should be tested for other STDs.
Treatment
Treating
infected patients prevents transmission to sex partners. In
addition, treating pregnant women usually prevents transmission
of C. trachomatis to infants during birth. Treatment of sex
partners helps to prevent reinfection of the index patient
and infection of other partners.
Coinfection
with C. trachomatis frequently occurs among patients who have
gonococcal infection; therefore, presumptive treatment of
such patients for chlamydia is appropriate (see Gonococcal
Infection, Dual Therapy for Gonococcal and Chlamydial Infections).
The following recommended treatment regimens and alternative
regimens cure infection and usually relieve symptoms.
Recommended
Regimens
Azithromycin 1 g orally in a single dose
OR
Doxycycline 100 mg orally twice a day for 7 days
Alternative Regimens
Erythromycin base 500 mg orally four times a day for 7 days
OR
Erythromycin ethylsuccinate 800 mg orally four times a day
for 7 days
OR
Ofloxacin 300 mg orally twice a day for 7 days
OR
Levofloxacin 500 mg orally once daily for 7 days
A
recent meta-analysis of 12 randomized clinical trials of azithromycin
versus doxycycline for the treatment of genital chlamydial
infection demonstrated that the treatments were equally efficacious,
with microbial cure rates of 97% and 98%, respectively. These
studies were conducted primarily in populations in which follow-up
was encouraged, adherence to a 7-day regimen was effective,
and culture or EIA (rather than the more sensitive NAAT was
used for determining microbiological outcome. Azithromycin
should always be available to treat patients for whom compliance
with multiday dosing is in question.
In
populations that have erratic health-care--seeking behavior,
poor treatment compliance, or unpredictable follow-up, azithromycin
might be more cost-effective because it enables the provision
of a single-dose of directly observed therapy. However, doxycycline
costs less than azithromycin and has no higher risk for adverse
events. Erythromycin might be less efficacious than either
azithromycin or doxycycline, mainly because of the frequent
occurrence of gastrointestinal side effects that discourage
compliance. Ofloxacin and levofloxacin are effective treatment
alternatives but are more expensive and offer no advantage
in the dosage regimen. Other quinolones either are not reliably
effective against chlamydial infection or have not been evaluated
adequately.
To
maximize compliance with recommended therapies, medications
for chlamydial infections should be dispensed on site, and
the first dose should be directly observed. To minimize transmission,
persons treated for chlamydia should be instructed to abstain
from sexual intercourse for 7 days after single-dose therapy
or until completion of a 7-day regimen. To minimize the risk
for reinfection, patients also should be instructed to abstain
from sexual intercourse until all of their sex partners are
treated.
Follow-up
Except
in pregnant women, test-of-cure (repeat testing 3--4 weeks
after completing therapy) is not recommended for persons treated
with the recommended or alterative regimens, unless therapeutic
compliance is in question, symptoms persist, or reinfection
is suspected. Moreover, the validity of chlamydial diagnostic
testing at <3 weeks after completion of therapy (to identify
patients who did not respond to therapy) has not been established.
False-negative results might occur because of persistent infections
involving limited numbers of chlamydial organisms. In addition,
NAAT conducted at <3 weeks after completion of therapy
in persons who were treated successfully could yield false-positive
results because of the continued presence of dead organisms.
A
high prevalence of C. trachomatis infection is observed in
women who were treated for chlamydial infection in the preceding
several months . The majority of posttreatment infections
result from reinfection, frequently occurring because the
patient's sex partners were not treated or because the patient
resumed sex with a new partner infected with C. trachomatis.
Repeat infections confer an elevated risk for PID and other
complications when compared with the initial infection. Therefore,
recently infected women are a major priority for repeat testing
for C. trachomatis. Clinicians and health-care agencies should
consider advising all women with chlamydial infection to be
retested approximately 3 months after treatment. Providers
also are strongly encouraged to retest all women treated for
chlamydial infection whenever they next seek medical care
within the following 3--12 months, regardless of whether the
patient believes that her sex partners were treated. Recognizing
that retesting is distinct from a test-of-cure, as discussed
in this report, is vital. Limited evidence is available on
the benefit of retesting for chlamydia in men previously infected;
however, some specialists suggest retesting men approximately
3 months after treatment.
Management
of Sex Partners
Patients
should be instructed to refer their sex partners for evaluation,
testing, and treatment. The following recommendations on exposure
intervals are based on limited evaluation. Sex partners should
be evaluated, tested, and treated if they had sexual contact
with the patient during the 60 days preceding onset of symptoms
in the patient or diagnosis of chlamydia. The most recent
sex partner should be evaluated and treated, even if the time
of the last sexual contact was >60 days before symptom
onset or diagnosis.
If
concerns exist that sex partners will not seek evaluation
and treatment, or if other management strategies are impractical
or unsuccessful, then delivery of antibiotic therapy (either
a prescription or medication) by heterosexual male or female
patients to their partners might be an option (see Partner
Notification). Limited studies to date have demonstrated a
trend toward a decrease in rates of persistent or recurrent
chlamydia with this approach compared with standard partner
referral. Male patients must inform female partners of their
infection and be given accompanying written materials about
the importance of seeking evaluation for PID (especially if
symptomatic). Patient-delivered partner therapy is not routinely
recommended for MSM because of a high risk for coexisting
infections, especially undiagnosed HIV infection, in their
partners.
Patients
should be instructed to abstain from sexual intercourse until
they and their sex partners have completed treatment. Abstinence
should be continued until 7 days after a single-dose regimen
or after completion of a 7-day regimen. Timely treatment of
sex partners is essential for decreasing the risk for reinfecting
the index patient.
Special
Considerations
Pregnancy.
Doxycycline, ofloxacin, and levofloxacin are contraindicated
in pregnant women. However, clinical experience and studies
suggest that azithromycin is safe and effective. Repeat testing
(preferably by NAAT) 3 weeks after completion of therapy with
the following regimens is recommended for all pregnant women
to ensure therapeutic cure, considering the sequelae that
might occur in the mother and neonate if the infection persists.
The frequent gastrointestinal side effects associated with
erythromycin might discourage patient compliance with the
alternative regimens.
Recommended
Regimens
Azithromycin 1 g orally in a single dose
OR
Amoxicillin 500 mg orally three times a day for 7 days
Alternative Regimens
Erythromycin base 500 mg orally four times a day for 7 days
OR
Erythromycin base 250 mg orally four times a day for 14 days
OR
Erythromycin ethylsuccinate 800 mg orally four times a day
for 7 days
OR
Erythromycin ethylsuccinate 400 mg orally four times a day
for 14 days
Erythromycin
estolate is contraindicated during pregnancy because of drug-related
hepatotoxicity. The lower dose 14-day erythromycin regimens
may be considered if gastrointestinal tolerance is a concern.
HIV
Infection. Patients who have chlamydial infection and also
are infected with HIV should receive the same treatment regimen
as those who are HIV negative.
Chlamydial
Infections Among Infants
Prenatal
screening of pregnant women can prevent chlamydial infection
among neonates. Pregnant women aged <25 years are at high
risk for infection. Local or regional prevalence surveys of
chlamydial infection can be conducted to confirm the utility
of using these recommendations in particular settings.
C.
trachomatis infection of neonates results from perinatal exposure
to the mother's infected cervix. Neonatal ocular prophylaxis
with silver nitrate solution or antibiotic ointments does
not prevent perinatal transmission of C. trachomatis from
mother to infant. However, ocular prophylaxis with those agents
does prevent gonococcal ophthalmia and, therefore, should
be continued (see Prevention of Ophthalmia Neonatorum).
Initial C. trachomatis perinatal infection involves the mucous
membranes of the eye, oropharynx, urogenital tract, and rectum
and might be asymptomatic in these locations. C. trachomatis
infection in neonates is most frequently recognized by conjunctivitis
that develops 5--12 days after birth. C. trachomatis also
can cause a subacute, afebrile pneumonia with onset at ages
1--3 months. C. trachomatis has been the most frequent identifiable
infectious cause of ophthalmia neonatorum, but perinatal chlamydial
infections, including opthalmia and pneumonia, are detected
less frequently because of the institution of widespread prenatal
screening and treatment of pregnant women.
Ophthalmia
Neonatorum Caused by C. trachomatis
A
chlamydial etiology should be considered for all infants aged
<30 days who have conjunctivitis, especially if the mother
has a history of untreated chlamydia infection.
Diagnostic
Considerations
Sensitive
and specific methods used to diagnose chlamydial ophthalmia
in the neonate include both tissue culture and nonculture
tests (e.g., DFA tests, EIA, and NAAT). The majority of nonculture
tests are not FDA-cleared for the detection of chlamydia from
conjunctival swabs, and clinical laboratories must verify
the procedure according to CLIA regulations. Specimens must
contain conjunctival cells, not exudate alone. Specimens for
culture isolation and nonculture tests should be obtained
from the everted eyelid using a dacron-tipped swab or the
swab specified by the manufacturer's test kit. A specific
diagnosis of C. trachomatis infection confirms the need for
treatment not only for the neonate but also for the mother
and her sex partner(s). Ocular exudate from infants being
evaluated for chlamydial conjunctivitis also should be tested
for N. gonorrhoeae.
Recommended
Regimen
Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided
into 4 doses daily for 14 days,***
Topical
antibiotic therapy alone is inadequate for treatment of chlamydial
infection and is unnecessary when systemic treatment is administered.
Follow-Up
The
efficacy of erythromycin treatment is approximately 80%; a
second course of therapy might be required and, therefore,
follow-up of infants is recommended to determine whether initial
treatment was effective. The possibility of concomitant chlamydial
pneumonia should be considered.
Management
of Mothers and Their Sex Partners
The
mothers of infants who have chlamydial infection and the sex
partners of these women should be evaluated and treated (see
Chlamydial Infection in Adolescents and Adults).
Infant
Pneumonia Caused by C. trachomatis
Characteristic
signs of chlamydial pneumonia in infants include 1) a repetitive
staccato cough with tachypnea and 2) hyperinflation and bilateral
diffuse infiltrates on a chest radiograph. Wheezing is rare,
and infants are typically afebrile. Peripheral eosinophilia
(>400 cells/mm3) occurs frequently. Because clinical presentations
differ, initial treatment and diagnostic tests should include
C. trachomatis for all infants aged 1--3 months who possibly
have pneumonia (especially with untreated maternal chlamydial
infection).
Diagnostic
Considerations
Specimens
for chlamydial testing should be collected from the nasopharynx.
Tissue culture is the definitive standard for chlamydial pneumonia.
Nonculture tests (e.g., EIA, DFA, and NAAT) can be used, although
nonculture tests of nasopharyngeal specimens have a lower
sensitivity and specificity than nonculture tests of ocular
specimens. DFA is the only FDA-cleared test for the detection
of C. trachomatis from nasopharyngeal specimens. Tracheal
aspirates and lung biopsy specimens, if collected, should
be tested for C. trachomatis.
Because
of the delay in obtaining test results for chlamydia, the
decision to provide treatment for C. trachomatis pneumonia
must frequently be based on clinical and radiologic findings.
The results of tests for chlamydial infection assist in the
management of an infant's illness and determine the need for
treating the mother and her sex partner(s).
Recommended
Regimen
Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided
into 4 doses daily for 14 days
Follow-Up
The
effectiveness of erythromycin in treating pneumonia caused
by C. trachomatis is approximately 80%; a second course of
therapy might be required. Follow-up of infants is recommended
to determine whether the pneumonia has resolved. Some infants
with chlamydial pneumonia have abnormal pulmonary function
tests later in childhood.
Management
of Mothers and Their Sex Partners
Mothers
of infants who have chlamydia pneumonia and the sex partners
of these women should be evaluated and treated according to
the recommended treatment of adults for chlamydial infections
(see Chlamydial Infection in Adolescents and Adults).
Infants
Born to Mothers Who Have Chlamydial Infection
Infants
born to mothers who have untreated chlamydia are at high risk
for infection; however, prophylatic antibiotic treatment is
not indicated, and the efficacy of such treatment is unknown.
Infants should be monitored to ensure appropriate treatment
if symptoms develop.
Chlamydial
Infections Among Children
Sexual
abuse must be considered a cause of chlamydial infection in
preadolescent children, although perinatally transmitted C.
trachomatis infection of the nasopharynx, urogenital tract,
and rectum might persist for >1 year (see Sexual Assault
or Abuse of Children).
Diagnostic
Considerations
Nonculture,
nonamplified probe tests for chlamydia (EIA, DFA) should not
be used because of the possibility of false-positive test
results. With respiratory tract specimens, false-positive
results can occur because of cross-reaction of test reagents
with C. pneumoniae; with genital and anal specimens, false-positive
results might occur because of cross-reaction with fecal flora.
Recommended
Regimens for Children Who Weigh <45 kg
Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided
into 4 doses daily for 14 days
Recommended
Regimen for Children Who Weigh >45 kg but Who Are Aged
>8 Years
Azithromycin 1 g orally in a single dose
Recommended
Regimens for Children Aged >8 years
Azithromycin 1 g orally in a single dose
OR
Doxycycline 100 mg orally twice a day for 7 days
Other
Management Considerations
See
Sexual Assault or Abuse of Children.
Follow-Up.
Follow-up cultures are necessary to ensure that treatment
has been effective.
Gonococcal
Infections in Adolescents and Adults
In
the United States, an estimated 600,000 new N. gonorrhoeae
infections occur each year (123). Gonorrhea is the second
most commonly reported bacterial STD. The majority of urethral
infections caused by N. gonorrhoeae among men produce symptoms
that cause them to seek curative treatment soon enough to
prevent serious sequelae, but treatment might not be soon
enough to prevent transmission to others. Among women, several
infections do not produce recognizable symptoms until complications
(e.g., PID) have occurred. Both symptomatic and asymptomatic
cases of PID can result in tubal scarring that can lead to
infertility or ectopic pregnancy.
Because
gonococcal infections among women frequently are asymptomatic,
an essential component of gonorrhea control in the United
States continues to be the screening of women at high risk
for STDs. The U.S. Preventive Services Task Force (USPSTF)
recommends that clinicians screen all sexually active women,
including those who are pregnant, for gonorrhea infection
if they are at increased risk. Women aged <25 years are
at highest risk for gonorrhea infection. Other risk factors
for gonorrhea include a previous gonorrhea infection, other
sexually transmitted infections, new or multiple sex partners,
inconsistent condom use, commercial sex work, and drug use.
The prevalence of gonorrhea infection varies widely among
communities and patient populations. The USPSTF does not recommend
screening for gonorrhea in men and women who are at low risk
for infection.
Diagnostic
Considerations
Because
of high specificity (>99%) and sensitivity (>95%), a
Gram stain of a male urethral specimen that demonstrates polymorphonuclear
leukocytes with intracellular Gram-negative diplococci can
be considered diagnostic for infection with N. gonorrhoeae
in symptomatic men. However, because of lower sensitivity,
a negative Gram stain should not be considered sufficient
for ruling out infection in asymptomatic men. In addition,
Gram stain of endocervical specimens, pharyngeal, or rectal
specimens also are not sufficient to detect infection and,
therefore, are not recommended. Specific testing for N. gonorrhoeae
is recommended because of the increased utility and availability
of highly sensitive and specific testing methods and because
a specific diagnosis might enhance partner notification.
Specific
diagnosis of infection with N. gonorrhoeae may be performed
by testing endocervical, vaginal, male urethral, or urine
specimens. Culture, nucleic acid hybridization tests, and
NAAT are available for the detection of genitourinary infection
with N. gonorrhoeae. Culture and nucleic acid hybridization
tests require female endocervical or male urethral swab specimens.
NAAT offer the widest range of testing specimen types because
they are FDA-cleared for use with endocervical swabs, vaginal
swabs, male urethral swabs, and female and male urine. However,
product inserts for each NAAT vendor must be carefully examined
to assess current indications because FDA-cleared specimen
types might vary. In general, culture is the most widely available
option for the diagnosis of infection with N. gonorrhoeae
in nongenital sites (e.g., rectum and pharynx). Nonculture
tests are not FDA-cleared for use in the rectum and pharynx.
Some NAATs have the potential to cross-react with nongonococcal
Neisseria and related organisms that are commonly found in
the throat. Some noncommercial laboratories have initiated
NAAT of rectal and pharyngeal swab specimens after establishing
the performance of the test to meet CLIA requirements.
Because
nonculture tests cannot provide antimicrobial susceptibility
results, in cases of persistent gonococcal infection after
treatment, clinicians should perform both culture and antimicrobial
susceptibility testing.
All
patients tested for gonorrhea should be tested for other STDs,
including chlamydia, syphilis, and HIV.
Dual
Therapy for Gonococcal and Chlamydial Infections
Patients
infected with N. gonorrhoeae frequently are coinfected with
C. trachomatis; this finding has led to the recommendation
that patients treated for gonococcal infection also be treated
routinely with a regimen that is effective against uncomplicated
genital C. trachomatis infection (135). Because the majority
of gonococci in the United States are susceptible to doxycycline
and azithromycin, routine cotreatment might also hinder the
development of antimicrobial-resistant N. gonorrhoeae.
Because
of the high sensitivity of NAATs for chlamydial infection,
patients with a negative chlamydial NAAT result at the time
of treatment for gonorrhea do not need to be treated for chlamydia
as well. However, if chlamydial test results are not available
or if a non-NAAT was negative for chlamydia, patients should
be treated for both gonorrhea and chlamydia.
Quinolone-Resistant
N. gonorrhoeae (QRNG)
QRNG
continues to spread, making the treatment of gonorrhea with
quinolones such as ciprofloxacin inadvisable in many areas
and populations. Resistance to ciprofloxacin usually indicates
resistance to other quinolones as well. QRNG is common in
parts of Europe, the Middle East, Asia, and the Pacific. In
the United States, QRNG is becoming increasingly common. Previously,
CDC had advised that quinolones not be used in California
and Hawaii because of the high prevalence of QRNG in these
areas. The prevalence of QRNG has increased in other areas
of the United States, which has resulted in changes in recommended
treatment regimens by other states and local areas. QRNG prevalence
will continue to increase, and quinolones will eventually
not be advisable for the treatment of gonorrhea. The CDC website
(http://www.cdc.gov/std/gisp)
or state health departments can provide the most current information.
In 2004, of 6,322 isolates collected by CDC's Gonococcal Isolate
Surveillance Project (GISP), 6.8% were resistant to ciprofloxacin
(minimum inhibitory concentrations [MICs] >1.0 µg/mL).
Excluding isolates from California and Hawaii, 3.6% of isolates
were QRNG. QRNG was more common among MSM than among heterosexual
men (23.9% versus 2.9%). In 2004, QRNG among heterosexual
men outside of California and Hawaii was 1.4%.
Quinolones
should not be used for the treatment of gonorrhea among MSM
or in areas with increased QRNG prevalence in the United States
(e.g., California and Hawaii) or for infections acquired while
traveling abroad. Because oral alternatives to quinolones
are limited, quinolones may continue to be used for heterosexual
men and women in areas and populations not known to have elevated
levels of resistance. Clinicians should obtain information
on the sexual behavior and recent travel history (including
histories from sex partners) of persons to be treated for
gonorrhea to ensure appropriate antibiotic therapy.
Resistance
of N. gonorrhoeae to fluoroquinolones and other antimicrobials
is expected to continue to spread; therefore, state and local
surveillance for antimicrobial resistance is crucial for guiding
local therapy recommendations. GISP, which samples approximately
3% of all U.S. men who have gonococcal infections, is a mainstay
of surveillance. However, surveillance by clinicians also
is critical. Clinicians who have diagnosed N. gonorrhoeae
infection in a person who was previously treated with a recommended
regimen and who probably has not been reexposed should perform
culture and susceptibility testing of relevant clinical specimens
and report the case to the local health department.
Uncomplicated
Gonococcal Infections of the Cervix, Urethra, and Rectum
Recommended
Regimens*
Ceftriaxone 125 mg IM in a single dose
OR
Cefixime 400 mg orally in a single dose
OR
Ciprofloxacin 500 mg orally in a single dose*
OR
Ofloxacin 400 mg orally in a single dose*
OR
Levofloxacin 250 mg orally in a single dose*
PLUS
TREATMENT FOR CHLAMYDIA IF CHLAMYDIAL INFECTION IS NOT RULED
OUT
*
Quinolones should not be used for infections in MSM or in
those with a history of recent foreign travel or partners'
travel, infections acquired in California or Hawaii, or infections
acquired in other areas with increased QRNG prevalence.
Recommended
Regimens for MSM or Heterosexuals with a History of Recent
Travel*
Ceftriaxone 125 mg IM in a single dose
OR
Cefixime 400 mg orally in a single dose
PLUS
TREATMENT FOR CHLAMYDIA IF CHLAMYDIAL INFECTION IS NOT RULED
OUT
*
Quinolones should not be used for infections in MSM or in
those with a history of recent foreign travel or partners'
travel, infections acquired in California or Hawaii, or infections
acquired in other areas with increased QRNG prevalence.
To
maximize compliance with recommended therapies, medications
for gonococcal infections should be dispensed on site.
Ceftriaxone
in a single injection of 125 mg provides sustained, high bactericidal
levels in the blood. Extensive clinical experience indicates
that ceftriaxone is safe and effective for the treatment of
uncomplicated gonorrhea at all anatomic sites, curing 98.9%
of uncomplicated urogenital and anorectal infections in published
clinical trials.
Cefixime
has an antimicrobial spectrum similar to that of ceftriaxone,
but the 400 mg oral dose does not provide as high, nor as
sustained, a bactericidal level as that provided by the 125
mg dose of ceftriaxone. In published clinical trials, the
400 mg dose cured 97.4% of uncomplicated urogenital and anorectal
gonococcal infections. The advantage of cefixime is that it
can be administered orally. Updates on the availability of
cefixime are available from CDC or state health departments.
Ciprofloxacin
is no longer universally effective against N. gonorrhoeae
in the United States. However, ciprofloxacin is safe, inexpensive,
and can be administered orally. In published clinical trials
of uncomplicated urogenital and anorectal infections in the
absence of QRNG, a dose of 500 mg of ciprofloxacin provides
sustained bactericidal levels with cure rates of 99.8%. If
QRNG is suspected, ceftriaxone IM or cefixime PO (by mouth)
should be used. If neither of these regimens are feasible
options, then one of the alternative nonquinolone regimens
in this report should be considered.
Similar to ciprofloxacin, ofloxacin is no longer universally
effective against N. gonorrhoeae in the United States. The
400 mg oral dose of ofloxacin has been effective for treatment
of uncomplicated urogenital and anorectal infections; in clinical
trials, 98.6% of infections were cured. Levofloxacin, the
active l-isomer of ofloxacin, can be used in place of ofloxacin
as a single dose of 250 mg.
Alternative
Regimens
Spectinomycin 2 g in a single IM dose
OR
Single-dose cephalosporin regimens
OR
Single-dose quinolone regimens
Several
other antimicrobials are active against N. gonorrhoeae, but
none have substantial advantages over the recommended regimens.
Spectinomycin is expensive and must be injected; however,
it has been effective in published clinical trials, curing
98.2% of uncomplicated urogenital and anorectal gonococcal
infections. Spectinomycin is useful for the treatment of patients
who cannot tolerate cephalosporins and quinolones.
Single-dose
cephalosporin regimens (other than ceftriaxone 125 mg IM and
cefixime 400 mg orally) that are safe and highly effective
against uncomplicated urogenital and anorectal gonococcal
infections include ceftizoxime (500 mg, administered IM),
cefoxitin (2 g, administered IM with probenecid 1 g orally),
and cefotaxime (500 mg, administered IM). None of the injectable
cephalosporins offer any advantage over ceftriaxone.
Single-dose
quinolone regimens include gatifloxacin 400 mg orally, norfloxacin
800 mg orally, and lomefloxacin 400 mg orally. These regimens
appear to be safe and effective for the treatment of uncomplicated
gonorrhea, but data regarding their use are limited. None
of the regimens appear to offer any advantage over ciprofloxacin,
ofloxacin, or levofloxacin, and they are not effective against
QRNG.
Some
evidence suggests that cefpodoxime and cefuroxime axetil 1
g orally might be additional oral alternatives in the treatment
of uncomplicated urogenital gonorrhea; additional information
on alternative oral regimens are available at http://www.cdc.gov/std.
Cefpodoxime proxetil 200 mg PO is less active against N. gonorrhoeae
than cefixime and also does not quite meet the minimum efficacy
criteria (demonstrated efficacy with lower 95% confidence
interval [CI] of >95% in summed clinical trials) with cure
rates, 96.5% (CI = 94.8%--98.9%) for urogenital and rectal
infection; efficacy in treating pharyngeal infection is unsatisfactory,
78.9% (CI = 54.5%--94%). Clinical studies are being conducted
to assess whether cefpodoxime 400 mg PO is an acceptable oral
alternative. Treatment with cefuroxime axetil 1 g PO does
not quite meet the minimum efficacy criteria for urogenital
and rectal infection (95.9%; CI = 94.5%--97.3%) and, its efficacy
in treating pharyngeal infection is unacceptable (56.9%; CI
= 42.2%--70.7%).
Azithromycin
2 g orally is effective against uncomplicated gonococcal infection
but is expensive and causes gastrointestinal distress and
is not recommended for treatment of gonorrhea. Although azithromycin
1 g theoretically meets alternative regimen criteria, it is
not recommended because of concerns regarding the possible
rapid emergence of antimicrobial resistance. N. gonorrhoeae
in the United States is not adequately susceptible to penicillins,
tetracyclines, and macrolides (e.g., erythromycin) for these
antimicrobials to be recommended.
Uncomplicated
Gonococcal Infections of the Pharynx
Gonococcal
infections of the pharynx are more difficult to eradicate
than infections at urogenital and anorectal sites. Few antimicrobial
regimens can reliably cure >90% of gonococcal pharyngeal
infections. Although chlamydial coinfection of the pharynx
is unusual, coinfection at genital sites sometimes occurs.
Therefore, treatment for both gonorrhea and chlamydia is recommended.
Recommended
Regimens*
Ceftriaxone 125 mg IM in a single dose
OR
Ciprofloxacin 500 mg orally in a single dose
PLUS
TREATMENT FOR CHLAMYDIA IF CHLAMYDIAL INFECTION IS NOT RULED
OUT
*
Quinolones should not be used for infections in MSM or in
those with a history of recent foreign travel or partners'
travel, infections acquired in California or Hawaii, or infections
acquired in other areas with increased QRNG prevalence.
Recommended
Regimens for MSM or Heterosexuals with a History of Recent
Travel
Ceftriaxone 125 mg IM in a single dose
PLUS
TREATMENT FOR CHLAMYDIA IN CHLAMYDIAL INFECTION IS NOT RULED
OUT
Follow-Up
Patients
who have uncomplicated gonorrhea and who are treated with
any of the recommended or alternative regimens do not need
a test of cure. Patients who have symptoms that persist after
treatment should be evaluated by culture for N. gonorrhoeae,
and any gonococci isolated should be tested for antimicrobial
susceptibility. Persistent urethritis, cervicitis, or proctitis
also might be caused by C. trachomatis or other organisms.
A
high prevalence of N. gonorrhoeae infection is observed in
patients who have had gonorrhea in the preceding several months.
The majority of infections identified after treatment with
one of the recommended regimens result from reinfection rather
than treatment failure, indicating a need for improved patient
education and referral of sex partners. Repeat infection might
confer an elevated risk for PID and other complications, when
compared with initial infection. Clinicians should consider
advising all patients with gonorrhea to be retested 3 months
after treatment. If patients do not seek medical care for
retesting in 3 months, providers are encouraged to test these
patients whenever they next seek medical care within the following
12 months, regardless of whether the patient believes that
their sex partners were treated. Retesting is distinct from
test of cure to detect therapeutic failure, which is not recommended.
Management
of Sex Partners
Effective
clinical management of patients with treatable STDs requires
treatment of the patients' recent sex partners to prevent
reinfection and curtail further transmission. Patients should
be instructed to refer their sex partners for evaluation and
treatment. Sex partners of patients with N. gonorrhoeae infection
whose last sexual contact with the patient was within 60 days
before onset of symptoms or diagnosis of infection in the
patient should be evaluated and treated for N. gonorrhoeae
and C. trachomatis infections. If a patient's last sexual
intercourse was >60 days before onset of symptoms or diagnosis,
the patient's most recent sex partner should be treated. Patients
should be instructed to avoid sexual intercourse until therapy
is completed and until they and their sex partners no longer
have symptoms.
For
patients with gonorrhea whose partners' treatment cannot be
ensured or is unlikely, delivery of antibiotic therapy (i.e.,
either a prescription or medication) by heterosexual male
or female patients to their partners is an option (see Partner
Notification). Use of this approach should always be accompanied
by efforts to educate partners about symptoms and to encourage
partners to seek clinical evaluation. Male patients must inform
female partners of their infection and be given accompanying
materials about the importance of seeking medical evaluation
for PID (especially if symptomatic). Possible undertreatment
of PID in female partners and possible missed opportunities
to diagnose other STDs are of concern and have not been evaluated
in comparisons with patient-delivered therapy and partner
referral. Patient-delivered therapy for patients with gonorrhea
should routinely include treatment for chlamydia. This approach
should not be considered a routine partner management strategy
in MSM because of the high risk of coexisting undiagnosed
STDs or HIV infection.
Special
Considerations
Allergy,
Intolerance, and Adverse Reactions
Persons who cannot tolerate cephalosporins or quinolones should
be treated with spectinomycin. Because spectinomycin is unreliable
(52% effective) against pharyngeal infections, patients who
have suspected or known pharyngeal infection should have a
pharyngeal culture 3--5 days after treatment to verify eradication
of infection.
Pregnancy
Pregnant
women should not be treated with quinolones or tetracyclines.
Those infected with N. gonorrhoeae should be treated with
a recommended or alternate cephalosporin. Women who cannot
tolerate a cephalosporin should be administered a single 2-g
dose of spectinomycin IM. Either azithromycin or amoxicillin
is recommended for treatment of presumptive or diagnosed C.
trachomatis infection during pregnancy (see Chlamydial Infections).
Administration
of Quinolones to Adolescents
Fluoroquinolones
have not been recommended for persons aged <18 years because
studies have indicated that they can damage articular cartilage
in some young animals. However, no joint damage attributable
to quinolone therapy has been observed in children treated
with prolonged ciprofloxacin regimens (143). Therefore, children
who weigh >45 kg can be treated with any regimen recommended
for adults (See Gonococcal Infections).
HIV
Infection
Patients
who have gonococcal infection and also are infected with HIV
should receive the same treatment regimen as those who are
HIV negative.
Gonococcal
Conjunctivitis
In
the only published study of the treatment of gonococcal conjunctivitis
among U.S. adults, all 12 study participants responded to
a single 1-g IM injection of ceftriaxone. The following recommendation
reflects the opinions of consultants knowledgeable in the
field of STDs.
Recommended
Regimen
Ceftriaxone 1 g IM in a single dose
Consider
lavage of the infected eye with saline solution once.
Management
of Sex Partners
Patients
should be instructed to refer their sex partners for evaluation
and treatment (see Gonococcal Infections, Management of Sex
Partners).
Disseminated
Gonococcal Infection (DGI)
DGI
results from gonococcal bacteremia. DGI frequently results
in petechial or pustular acral skin lesions, asymmetrical
arthralgia, tenosynovitis, or septic arthritis. The infection
is complicated occasionally by perihepatitis and rarely by
endocarditis or meningitis. Some strains of N. gonorrhoeae
that cause DGI may cause minimal genital inflammation.
No
studies on the treatment of DGI among adults have been published
since publication of the last CDC STD treatment guidelines
publication. DGI treatment recommendations reflect the opinions
of consultants. No treatment failures have been reported with
the recommended regimens.
Treatment
Hospitalization
is recommended for initial therapy, especially for patients
who might not comply with treatment, for those in whom diagnosis
is uncertain, and for those who have purulent synovial effusions
or other complications. Patients should be examined for clinical
evidence of endocarditis and meningitis. Patients treated
for DGI should be treated presumptively for concurrent C.
trachomatis infection, unless appropriate testing excludes
this infection.
Recommended
Regimen
Ceftriaxone 1 g IM or IV every 24 hours
Alternative Regimens
Cefotaxime 1 g IV every 8 hours
OR
Ceftizoxime 1 g IV every 8 hours
OR
Ciprofloxacin 400 mg IV every 12 hours*
OR
Ofloxacin 400 mg IV every 12 hours*
OR
Levofloxacin 250 mg IV daily*
OR
Spectinomycin 2 g IM every 12 hours
*
Quinolones should not be used for infections in MSM or in
those with a history of recent foreign travel or partners'
travel, infections acquired in California or Hawaii, or infections
acquired in other areas with increased QRNG prevalence.
All
of the preceding regimens should be continued for 24--48 hours
after improvement begins, at which time therapy may be switched
to one of the following regimens to complete at least 1 week
of antimicrobial therapy.
Cefixime
400 mg orally twice daily
OR
Ciprofloxacin 500 mg orally twice daily*
OR
Ofloxacin 400 mg orally twice daily*
OR
Levofloxacin 500 mg orally once daily*
*
Quinolones should not be used for infections in MSM or in
those with a history of recent foreign travel or partners'
travel, infections acquired in California or Hawaii, or infections
acquired in other areas with increased QRNG prevalence.
Management
of Sex Partners
Gonococcal
infection frequently is asymptomatic in sex partners of patients
who have DGI. As with uncomplicated gonococcal infections,
patients should be instructed to refer their sex partners
for evaluation and treatment (see Gonococcal Infection, Management
of Sex Partners).
Gonococcal
Meningitis and Endocarditis
Recommended
Regimen
Ceftriaxone 1--2 g IV every 12 hours
Therapy
for meningitis should be continued for 10--14 days; therapy
for endocarditis should be continued for at least 4 weeks.
Treatment of complicated DGI should be undertaken in consultation
with a specialist.
Management
of Sex Partners
Patients
should be instructed to refer their sex partners for evaluation
and treatment (see Gonococcal Infection, Management of Sex
Partners).
Gonococcal
Infections Among Infants
Gonococcal
infection among infants usually results from exposure to infected
cervical exudate at birth. It is usually an acute illness
that manifests 2--5 days after birth. The prevalence of infection
among infants depends on the prevalence of infection among
pregnant women, whether pregnant women are screened for gonorrhea,
and whether newborns receive ophthalmia prophylaxis. The most
severe manifestations of N. gonorrhoeae infection in newborns
are ophthalmia neonatorum and sepsis, which can include arthritis
and meningitis. Less severe manifestations include rhinitis,
vaginitis, urethritis, and reinfection at sites of fetal monitoring.
Ophthalmia
Neonatorum Caused by N. gonorrhoeae
In
the United States, although N. gonorrhoeae causes ophthalmia
neonatorum less frequently than C. trachomatis and nonsexually
transmitted agents, identifying and treating this infection
is especially important because ophthalmia neonatorum can
result in perforation of the globe of the eye and blindness.
Diagnostic
Considerations
Infants
at increased risk for gonococcal ophthalmia are those who
do not receive ophthalmia prophylaxis and those whose mothers
have had no prenatal care or whose mothers have a history
of STDs or substance abuse. Gonococcal ophthalmia is strongly
suspected when intracellular gram-negative diplococci are
identified in conjunctival exudate, justifying presumptive
treatment for gonorrhea after appropriate cultures for N.
gonorrhoeae are obtained. Appropriate chlamydial testing should
be done simultaneously. Presumptive treatment for N. gonorrhoeae
might be indicated for newborns who are at increased risk
for gonococcal ophthalmia and who have conjunctivitis but
do not have gonococci in a Gram-stained smear of conjunctival
exudate.
In
all cases of neonatal conjunctivitis, conjunctival exudates
should be cultured for N. gonorrhoeae and tested for antibiotic
susceptibility before a definitive diagnosis is made. A definitive
diagnosis is vital because of the public health and social
consequences of a diagnosis of gonorrhea. Nongonococcal causes
of neonatal ophthalmia include Moraxella catarrhalis and other
Neisseria species that are indistinguishable from N. gonorrhoeae
on Gram-stained smear but can be differentiated in the microbiology
laboratory.
Recommended
Regimen
Ceftriaxone 25--50 mg/kg IV or IM in a single dose, not to
exceed 125 mg
Topical
antibiotic therapy alone is inadequate and is unnecessary
if systemic treatment is administered.
Other
Management Considerations
Simultaneous
infection with C. trachomatis should be considered when a
patient does not improve after treatment. Both mother and
infant should be tested for chlamydial infection at the same
time that gonorrhea testing is conducted (see Ophthalmia Neonatorum
Caused by C. trachomatis). Ceftriaxone should be administered
cautiously to hyperbilirubinemic infants, especially those
born prematurely.
Follow-Up
Infants
who have gonococcal ophthalmia should be hospitalized and
evaluated for signs of disseminated infection (e.g., sepsis,
arthritis, and meningitis). One dose of ceftriaxone is adequate
therapy for gonococcal conjunctivitis.
Management
of Mothers and Their Sex Partners
The
mothers of infants who have gonococcal infection and the mothers'
sex partners should be evaluated and treated according to
the recommendations for treating gonococcal infections in
adults (see Gonococcal Infections in Adolescents and Adults).
DGI
and Gonococcal Scalp Abscesses in Newborns
Sepsis,
arthritis, and meningitis (or any combination of these conditions)
are rare complications of neonatal gonococcal infection. Localized
gonococcal infection of the scalp can result from fetal monitoring
through scalp electrodes. Detection of gonococcal infection
in neonates who have sepsis, arthritis, meningitis, or scalp
abscesses requires cultures of blood, CSF, and joint aspirate
on chocolate agar. Specimens obtained from the conjunctiva,
vagina, oropharynx, and rectum that are cultured on gonococcal
selective medium are useful for identifying the primary site(s)
of infection, especially if inflammation is present. Positive
Gram-stained smears of exudate, CSF, or joint aspirate provide
a presumptive basis for initiating treatment for N. gonorrhoeae.
Diagnoses based on Gram-stained smears or presumptive identification
of cultures should be confirmed with definitive tests on culture
isolates.
Recommended
Regimens
Ceftriaxone 25--50 mg/kg/day IV or IM in a single daily dose
for 7 days, with a duration of 10--14 days, if meningitis
is documented
OR
Cefotaxime 25 mg/kg IV or IM every 12 hours for 7 days, with
a duration of 10--14 days, if meningitis is documented
Prophylactic
Treatment for Infants Whose Mothers Have Gonococcal Infection
Infants
born to mothers who have untreated gonorrhea are at high risk
for infection.
Recommended
Regimen in the Absence of Signs of Gonococcal Infection
Ceftriaxone 25--50 mg/kg IV or IM, not to exceed 125 mg, in
a single dose
Other
Management Considerations
Both
mother and infant should be tested for chlamydial infection.
Follow-Up
Follow-up examination is not required.
Management
of Mothers and Their Sex Partners
The
mothers of infants who have gonococcal infection and the mothers'
sex partners should be evaluated and treated according to
the recommendations for treatment of gonococcal infections
in adults (see Gonococcal Infections).
Gonococcal
Infections Among Children
Sexual
abuse is the most frequent cause of gonococcal infection in
pre-adolescent children (see Sexual Assault or Abuse of Children).
Vaginitis is the most common manifestation of gonococcal infection
in preadolescent girls. PID after vaginal infection is probably
less common in children than among adults. Among sexually
abused children, anorectal and pharyngeal infections with
N. gonorrhoeae are common and frequently asymptomatic.
Diagnostic
Considerations
Because
of the legal implications of a diagnosis of N. gonorrhoeae
infection in a child, only standard culture procedures for
the isolation of N. gonorrhoeae should be used for children.
Nonculture gonococcal tests for gonococci (e.g., Gram-stained
smear, nucleic acid hybridization tests, EIA, and NAAT) should
not be used without standard culture; none of these tests
have been approved by FDA for use with specimens obtained
from the oropharynx, rectum, or genital tract of children.
Specimens from the vagina, urethra, pharynx, or rectum should
be streaked onto selective media for isolation of N. gonorrhoeae,
and all presumptive isolates of N. gonorrhoeae should be identified
definitively by at least two tests that involve different
principles (e.g., biochemical, enzyme substrate, or serologic).
Isolates should be preserved to enable additional or repeated
testing.
Recommended
Regimens for Children Who Weigh >45 kg
Treat with one of the regimens recommended for adults (see
Gonococcal Infections)
Fluoroquinolones
have not been recommended for persons aged <18 years because
they have damaged articular cartilage in young animals. However,
no such joint damage clearly attributable to quinolone therapy
has been observed in children, even in those receiving multiple-dose
regimens.
Recommended
Regimens for Children Who Weigh <45 kg and Who Have Uncomplicated
Gonococcal Vulvovaginitis,
Cervicitis, Urethritis, Pharyngitis, or Proctitis
Ceftriaxone 125 mg IM in a single dose
Alternative
Regimen
Spectinomycin 40 mg/kg (maximum dose: 2 g) IM in a single
dose may be used, but this therapy is unreliable for treatment
of pharyngeal infections. Some specialists use cefixime to
treat gonococcal infections in children because it can be
administered orally; however, no reports have been published
concerning the safety or effectiveness of cefixime used for
this purpose.
Recommended
Regimen for Children Who Weigh <45 kg and Who Have Bacteremia
or Arthritis
Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM or IV in a single
dose daily for 7 days
Recommended
Regimen for Children Who Weigh >45 kg and Who Have Bacteremia
or Arthritis
Ceftriaxone 50 mg/kg IM or IV in a single dose daily for 7
days
Follow-Up
Follow-up
cultures are unnecessary if ceftriaxone is used. If spectinomycin
is used to treat pharyngitis, a follow-up culture is necessary
to ensure that treatment was effective.
Other
Management Considerations
Only
parenteral cephalosporins are recommended for use in children.
Ceftriaxone is approved for all gonococcal infections in children;
cefotaxime is approved for gonococcal ophthalmia only. Oral
cephalosporins used for treatment of gonococcal infections
in children have not been adequately evaluated.
All
children who have gonococcal infections should be evaluated
for coinfection with syphilis and C. trachomatis. (For a discussion
of concerns regarding sexual assault, refer to Sexual Assault
or Abuse of Children).
Ophthalmia
Neonatorum Prophylaxis
To
prevent gonococcal ophthalmia neonatorum, a prophylactic agent
should be instilled into the eyes of all newborn infants;
this procedure is required by law in the majority of states.
All of the recommended prophylactic regimens in this section
prevent gonococcal ophthalmia. However, the efficacy of these
preparations in preventing chlamydial ophthalmia is less clear,
and they do not eliminate nasopharyngeal colonization by C.
trachomatis. The diagnosis and treatment of gonococcal and
chlamydial infections in pregnant women is the best method
for preventing neonatal gonococcal and chlamydial disease.
Not all women, however, receive prenatal care. Ocular prophylaxis
is warranted because it can prevent sight-threatening gonococcal
ophthalmia and because it is safe, easy to administer, and
inexpensive.
Prophylaxis
Recommended
Regimens
Erythromycin (0.5%) ophthalmic ointment in a single application
OR
Tetracycline ophthalmic ointment (1%) in a single application
One
of these recommended preparations should be instilled into
both eyes of every neonate as soon as possible after delivery.
If prophylaxis is delayed (i.e., not administered in the delivery
room), a monitoring system should be established to ensure
that all infants receive prophylaxis. All infants should be
administered ocular prophylaxis, regardless of whether they
are delivered vaginally or by cesarean section. Single-use
tubes or ampules are preferable to multiple-use tubes. Bacitracin
is not effective. Use of povidone iodine has not been studied
adequately.
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Diseases
Characterized by Vaginal Discharge
|
Management
of Patients Who Have Vaginal Infections
Vaginitis
is usually characterized by a vaginal discharge and/or vulvar
itching and irritation, and a vaginal odor might be present.
The three diseases most frequently associated with vaginal
discharge are BV (replacement of the normal vaginal flora
by an overgrowth of anaerobic microorganisms, mycoplasmas,
and Gardnerella vaginalis), trichomoniasis (T. vaginalis),
and candidiasis (usually caused by Candida albicans). Cervicitis
can sometimes cause a vaginal discharge. Although vulvovaginal
candidiasis (VVC) usually is not transmitted sexually, it
is included in this section because it is frequently diagnosed
in women being evaluated for STDs.
Various
diagnostic methods are available to identify the etiology
of an abnormal vaginal discharge. Laboratory testing fails
to identify the cause of vaginitis in a minority of women.
The cause of vaginal symptoms usually can be determined by
pH and microscopic examination of fresh samples of the discharge.
The pH of the vaginal secretions can be determined by narrow-range
pH paper; an elevated pH (i.e., >4.5) is common with BV
or trichomoniasis but might not be highly specific. Discharge
can be further examined by diluting one sample in one to two
drops of 0.9% normal saline solution on one slide and a second
sample in 10% potassium hydroxide (KOH) solution. An amine
odor detected immediately after applying KOH suggests BV.
Cover
slips are placed on the slides, and they are examined under
a microscope at low- and high-dry power. Motile T. vaginalis
or clue cells (epithelial cells with borders obscured by small
bacteria), which are characteristic of BV, usually are identified
easily in the saline specimen. WBCs without evidence of trichomonads
or yeast are usually suggestive of cervicitis (see Cervicitis).
The yeast or pseudohyphae of Candida species are more easily
identified in the KOH specimen. However, the absence of trichomonads
or pseudohyphae does not rule out these infections because
several studies have demonstrated the presence of these pathogens
by culture or PCR after a negative microscopic examination.
The presence of objective signs of vulvar inflammation in
the absence of vaginal pathogens, along with a minimal amount
of discharge, suggests the possibility of mechanical, chemical,
allergic, or other noninfectious irritation of the vulva.
Culture for T. vaginalis is more sensitive than microscopic
examination. In settings where microscopy is not available,
alternative point-of-care tests may be used to diagnose vaginitis.
Bacterial
Vaginosis
BV
is a polymicrobial clinical syndrome resulting from replacement
of the normal H2O2--producing Lactobacillus sp. in the vagina
with high concentrations of anaerobic bacteria (e.g., Prevotella
sp. and Mobiluncus sp.), G. vaginalis, and Mycoplasma hominis.
BV is the most prevalent cause of vaginal discharge or malodor;
however, more than 50% of women with BV are asymptomatic.
The cause of the microbial alteration is not fully understood.
BV is associated with having multiple sex partners, a new
sex partner, douching, and lack of vaginal lactobacilli; whether
BV results from acquisition of a sexually transmitted pathogen
is unclear. Women who have never been sexually active are
rarely affected. Treatment of male sex partners has not been
beneficial in preventing the recurrence of BV.
Diagnostic
Considerations
BV
can be diagnosed by the use of clinical criteria or Gram stain.
Clinical criteria require three of the following symptoms
or signs:
- homogeneous,
thin, white discharge that smoothly coats the vaginal walls;
- presence
of clue cells on microscopic examination;
- pH
of vaginal fluid >4.5; and
- a
fishy odor of vaginal discharge before or after addition
of 10% KOH (i.e., the whiff test).
When
a Gram stain is used, determining the relative concentration
of lactobacilli (long Gram-positive rods), Gram-negative and
Gram-variable rods and cocci (i.e., G. vaginalis, Prevotella,
Porphyromonas, and peptostreptococci), and curved Gram-negative
rods (Mobiluncus) characteristic of BV is considered the gold
standard laboratory method for diagnosing BV. Culture of G.
vaginalis is not recommended as a diagnostic tool because
it is not specific. However, a DNA probe-based test for high
concentrations of G. vaginalis (AffirmTM VP III, Becton Dickinson,
Sparks, Maryland) might have clinical utility. Cervical Pap
tests have no clinical utility for the diagnosis of BV because
of low sensitivity. Other commercially available tests that
might be useful for the diagnosis of BV include a card test
for the detection of elevated pH and trimethylamine (QuickVue
Advance Quidel, San Diego, California) and prolineaminopeptidase
(Pip Activity TestCardTM, Quidel, San Diego, California).
Treatment
The
established benefits of therapy for BV in nonpregnant women
are to 1) relieve vaginal symptoms and signs of infection
and 2) reduce the risk for infectious complications after
abortion or hysterectomy. Other potential benefits might include
a reduction in risk for other infections (e.g., HIV and other
STDs). All women who have symptomatic disease require treatment.
BV
during pregnancy is associated with adverse pregnancy outcomes,
including premature rupture of the membranes, preterm labor,
preterm birth, intraamniotic infection, and postpartum endometritis.
The established benefit of therapy for BV in pregnant women
is to relieve vaginal symptoms and signs of infection. Additional
potential benefits of therapy include 1) reducing the risk
for infectious complications associated with BV during pregnancy
and 2) reducing the risk for other infections (e.g., other
STDs or HIV). The results of several investigations indicate
that treatment of pregnant women with BV who are at high risk
for preterm delivery (i.e., those who previously delivered
a premature infant) might reduce the risk for prematurity.
Therefore, clinicians should consider evaluation and treatment
of high-risk pregnant women with asymptomatic BV.
The
bacterial flora that characterizes BV have been recovered
from the endometria and salpinges of women who have PID. BV
has been associated with endometritis, PID, and vaginal cuff
cellulitis after invasive procedures, including endometrial
biopsy, hysterectomy, hysterosalpingography, placement of
an IUD, cesarean section, and uterine curettage. The results
of two randomized controlled trials have indicated that treatment
of BV with metronidazole substantially reduced postabortion.
Three
trials that evaluated the use of anaerobic antimicrobial coverage
(i.e., metronidazole) for routine operative prophylaxis before
abortion and seven trials that evaluated this additional coverage
for women undergoing hysterectomy demonstrated a substantial
reduction in postoperative infectious complications. Because
of the increased risk for postoperative infectious complications
associated with BV, some specialists recommend that before
performing surgical abortion or hysterectomy, providers should
screen and treat women with BV in addition to providing routine
prophylaxis. However, more information is needed before recommending
treatment of asymptomatic BV before other invasive procedures.
Recommended
Regimens
Metronidazole 500 mg orally twice a day for 7 days
OR
Metronidazole gel, 0.75%, one full applicator (5g) intravaginally,
once a day for 5 days
OR
Clindamycin cream, 2%, one full applicator (5g) intravaginally
at bedtime for 7 days
Patients
should be advised to avoid consuming alcohol during treatment
with metronidazole and for 24 hours thereafter. Clindamycin
cream is oil-based and might weaken latex condoms and diaphragms
for 5 days after use. Refer to clindamycin product labeling
for additional information. Topical clindamycin preparations
should not be used in the second half of pregnancy.
The recommended metronidazole regimens are equally efficacious.
The recommended intravaginal clindamycin regimen might be
less efficacious than the metronidazole regimens. One randomized
trial evaluated the clinical equivalency of intravaginal metronidazole
gel 0.75% once daily versus twice daily and demonstrated similar
cure rates 1 month after therapy.
Alternative
Regimens
Clindamycin 300 mg orally twice a day for 7 days
OR
Clindamycin ovules 100 g intravaginally once at bedtime for
3 days
Metronidazole
2 g single-dose therapy has the lowest efficacy for BV and
is no longer a recommended or alternative regimen. FDA has
cleared metronidazole 750 mg extended release tablets once
daily for 7 days and a single dose of clindamycin intravaginal
cream. No data have been published that compares the clinical
or microbiologic equivalencies of these regimens with other
regimens. Cure rates do not differ between intravaginal clindamycin
cream and ovules.
Several
studies have evaluated the clinical and microbiologic efficacy
of using lactobacillus intravaginal suppositories to restore
normal flora and treat BV. However, no currently available
lactobacillus suppository was determined to be better than
placebo 1 month after therapy for either clinical or microbiologic
cure. No data support the use of douching for treatment or
relief of symptoms.
Follow-Up
Follow-up
visits are unnecessary if symptoms resolve. Because recurrence
of BV is not unusual, women should be advised to return for
additional therapy if symptoms recur. A treatment regimen
different from the original regimen may be used to treat recurrent
disease. However, women with multiple recurrences should be
managed in consultation with a specialist. One randomized
trial for persistent BV indicated that metronidazole gel 0.75%
twice per week for 6 months after completion of a recommended
regimen was effective in maintaining a clinical cure for 6
months.
Management
of Sex Partners
The
results of clinical trials indicate that a woman's response
to therapy and the likelihood of relapse or recurrence are
not affected by treatment of her sex partner(s). Therefore,
routine treatment of sex partners is not recommended.
Special
Considerations
Allergy
or Intolerance to the Recommended Therapy
Intravaginal
clindamycin cream is preferred in case of allergy or intolerance
to metronidazole. Intravaginal metronidazole gel can be considered
for patients who do not tolerate systemic metronidazole, but
patients allergic to oral metronidazole should not be administered
intravaginal metronidazole.
Pregnancy
All
pregnant women who have symptomatic disease require treatment.
BV has been associated with adverse pregnancy outcomes (e.g.,
premature rupture of the membranes, chorioamnionitis, preterm
labor, preterm birth, intraamniotic infection, postpartum
endometritis, and postcesarean wound infection). Some specialists
prefer using systemic therapy to treat possible subclinical
upper genital tract infections.
Treatment
of BV in asymptomatic pregnant women at high risk for preterm
delivery (i.e., those who have previously delivered a premature
infant) with a recommended oral regimen has reduced preterm
delivery in three of four randomized controlled trials; some
specialists recommend screening and oral treatment of these
women. However, the optimal treatment regimens have not been
established. Screening (if conducted) and treatment should
be performed during the first prenatal visit.
Two
trials that evaluated the efficacy of metronidazole during
pregnancy used the 250-mg regimen. However, some specialists
suggest using a regimen of 500 mg twice daily in pregnant
women. One small trial demonstrated that treatment with oral
metronidazole 500 mg twice daily was equally effective as
metronidazole gel, with cure rates of 70%. These regimens
were not effective in reducing preterm birth in any group
of women. Multiple studies and meta-analyses have not demonstrated
an association between metronidazole use during pregnancy
and teratogenic or mutagenic effects in newborns.
Recommended
Regimens for Pregnant Women
Metronidazole 500 mg orally twice a day for 7 days
OR
Metronidazole 250 mg orally three times a day for 7 days
OR
Clindamycin 300 mg orally twice a day for 7 days
Whether
treatment of asymptomatic pregnant women with BV who are at
low risk for preterm delivery reduces adverse outcomes of
pregnancy is unclear. One trial in which oral clindamycin
was used demonstrated a reduction in spontaneous preterm birth.
Several trials have evaluated the use of intravaginal clindamycin
during pregnancy to reduce preterm birth and treat asymptomatic
BV. One trial in which women were treated before 20 weeks'
gestation demonstrated a reduction in preterm birth. In three
other trials, intravaginal clindamycin cream was administered
at 16--32 weeks' gestation, and an increase in adverse events
(e.g., low birthweight and neonatal infections) was observed
in newborns. Therefore, intravaginal clindamycin cream should
only be used during the first half of pregnancy.
Follow-Up
of Pregnant Women
Treatment
of BV in asymptomatic pregnant women who are at high risk
for preterm delivery might prevent adverse pregnancy outcomes.
Therefore, a follow-up evaluation 1 month after completion
of treatment should be considered to evaluate whether therapy
was effective.
HIV
Infection
Patients
who have BV and also are infected with HIV should receive
the same treatment regimen as those who are HIV negative.
BV appears to be more persistent in HIV-positive women.
Trichomoniasis
Trichomoniasis
is caused by the protozoan T. vaginalis. Some men who are
infected with T. vaginalis might not have symptoms; others
have NGU. Many infected women have symptoms characterized
by a diffuse, malodorous, yellow-green vaginal discharge with
vulvar irritation. However, some women have minimal or no
symptoms.
Diagnosis
of vaginal trichomoniasis is usually performed by microscopy
of vaginal secretions, but this method has a sensitivity of
only approximately 60%--70% and requires immediate evaluation
of wet preparation slide for optimal results. Other FDA-cleared
tests for trichomoniasis in women include OSOM Trichomonas
Rapid Test (Genzyme Diagnostics, Cambridge, Massachusetts),
an immunochromatographic capillary flow dipstick technology,
and the Affirm VP III (Becton Dickenson, San Jose, California),
a nucleic acid probe test that evaluates for T. vaginalis,
G. vaginalis, and C. albicans. These tests are both performed
on vaginal secretions and have a sensitivity >83% and a
specificity >97%. Both tests are point-of-care diagnostics.
The results of the OSOM Trichomonas Rapid Test are available
in approximately 10 minutes, and results of the Affirm
VP III are available within 45 minutes. Although these tests
tend to be more sensitive than vaginal wet preparation, false
positives might occur especially in low prevalence populations.
Culture is the most sensitive and specific commercially available
method of diagnosis. In women in whom trichomoniasis is suspected
but not confirmed by microscopy, vaginal secretions should
be cultured for T. vaginalis.
In
men, wet preparation is insensitive, and culture testing of
urethral swab, urine, and semen is required for optimal sensitivity.
No FDA-cleared PCR test for T. vaginalis is available in the
United States, but such testing might be available from commercial
laboratories that have developed their own PCR tests.
Recommended
Regimens
Metronidazole 2 g orally in a single dose
OR
Tinidazole 2 g orally in a single dose
Alternative
Regimen
Metronidazole 500 mg orally twice a day for 7 days
Patients
should be advised to avoid consuming alcohol during treatment
with metronidazole or tinidazole. Abstinence from alcohol
use should continue for 24 hours after completion of metronidazole
or 72 hours after completion of tinidazole.
The
nitroimidazoles comprise the only class of drugs useful for
the oral or parenteral therapy of trichomoniasis. Of these
drugs, metronidazole and tinidazole are available in the United
States and are cleared by the FDA for the treatment of trichomoniasis.
In randomized clinical trials, the recommended metronidazole
regimens have resulted in cure rates of approximately 90%--95%,
and the recommended tinidazole regimen has resulted in cure
rates of approximately 86%--100%. The appropriate treatment
of sex partners might increase these reported rates. Randomized
controlled trials comparing single 2 g doses of metronidazole
and tinidazole suggest that tinidazole is equivalent to, or
superior to, metronidazole in achieving parasitologic cure
and resolution of symptoms. Treatment of patients and sex
partners results in relief of symptoms, microbiologic cure,
and reduction of transmission.
Metronidazole
gel is considerably less efficacious for the treatment of
trichomoniasis (<50%) than oral preparations of metronidazole.
Topically applied antimicrobials (e.g., metronidazole gel)
are unlikely to achieve therapeutic levels in the urethra
or perivaginal glands; therefore, use of the gel is not recommended.
Several other topically applied antimicrobials occasionally
have been used for treatment of trichomoniasis; however, these
preparations probably do not have greater efficacy than metronidazole
gel.
Follow-Up
Follow-up
is unnecessary for men and women who become asymptomatic after
treatment or who are initially asymptomatic. Some strains
of T. vaginalis can have diminished susceptibility to metronidazole;
however, infections caused by the majority of these organisms
respond to tinidazole or higher doses of metronidazole. Low-level
metronidazole resistance has been identified in 2%--5% of
cases of vaginal trichomoniasis. High-level resistance is
rare. Tinidazole has a longer serum half-life and reaches
higher levels in genitourinary tissues than metronidazole.
In addition, many T. vaginalis isolates have lower minimum
inhibitory concentrations (MICs) to tinidazole than metronidazole.
If
treatment failure occurs with metronidazole 2 g single dose
and reinfection is excluded, the patient can be treated with
metronidazole 500 mg orally twice daily for 7 days or tinidazole
2 g single dose. For patients failing either of these regimens,
clinicians should consider treatment with tinidazole or metronidazole
at 2 g orally for 5 days. If these therapies are not effective,
further management should be discussed with a specialist.
The consultation should ideally include determination of the
susceptibility of T. vaginalis to metronidazole and tinidazole.
Consultation and T. vaginalis susceptibility testing is available
from CDC (telephone: 770-488-4115; website: http://www.cdc.gov/std).
Management
of Sex Partners
Sex
partners of patients with T. vaginalis should be treated.
Patients should be instructed to avoid sex until they and
their sex partners are cured (i.e., when therapy has been
completed and patient and partner(s) are asymptomatic).
Special
Considerations
Allergy,
Intolerance, and Adverse Reactions
Metronidazole
and tinidazole are both nitroimidazoles. Patients with an
immediate-type allergy to a nitroimidazole can be managed
by metronidazole desensitization in consultation with a specialist
(171,172). Topical therapy with drugs other than nitroimidazoles
can be attempted, but cure rates are low (<50%).
Pregnancy
Vaginal
trichomoniasis has been associated with adverse pregnancy
outcomes, particularly premature rupture of membranes, preterm
delivery, and low birthweight. However, data do not suggest
that metronidazole treatment results in a reduction in perinatal
morbidity. Although some trials suggest the possibility of
increased prematurity or low birthweight after metronidazole
treatment, limitations of the studies prevent definitive conclusions
regarding risks of treatment. Treatment of T. vaginalis might
relieve symptoms of vaginal discharge in pregnant women and
might prevent respiratory or genital infection of the newborn
and further sexual transmission. Clinicians should counsel
patients regarding the potential risks and benefits of treatment.
Some specialists would defer therapy in asymptomatic pregnant
women until after 37 weeks' gestation. In addition, these
pregnant women should be provided careful counseling regarding
condom use and the continued risk of sexual transmission.
Women
may be treated with 2 g of metronidazole in a single dose.
Metronidazole is pregnancy category B (animal studies have
revealed no evidence of harm to the fetus, but no adequate,
well-controlled studies among pregnant women have been conducted).
Multiple studies and meta-analyses have not demonstrated a
consistent association between metronidazole use during pregnancy
and teratogenic or mutagenic effects in infants. Tinidazole
is pregnancy category C (animal studies have demonstrated
an adverse event, and no adequate, well-controlled studies
in pregnant women have been conducted), and its safety in
pregnant women has not been well-evaluated.
In
lactating women who are administered metronidazole, withholding
breastfeeding during treatment and for 12--24 hours after
the last dose will reduce the exposure of metronidazole to
the infant. While using tinidazole, interruption of breastfeeding
is recommended during treatment and for 3 days after the last
dose.
HIV
Infection
Patients
who have trichomoniasis and also are infected with HIV should
receive the same treatment regimen as those who are HIV negative.
The incidence, persistence, and recurrence of trichomoniasis
in HIV-infected women are not correlated with immune status.
Vulvovaginal
Candidiasis
VVC
usually is caused by C. albicans but occasionally is caused
by other Candida sp. or yeasts. Typical symptoms of VVC include
pruritus, vaginal soreness, dyspareunia, external dysuria,
and abnormal vaginal discharge. None of these symptoms is
specific for VVC. An estimated 75% of women will have at least
one episode of VVC, and 40%--45% will have two or more episodes.
On the basis of clinical presentation, microbiology, host
factors, and response to therapy, VVC can be classified as
either uncomplicated or complicated (Box 2). Approximately
10%--20% of women will have complicated VVC, suggesting diagnostic
and therapeutic considerations.
Uncomplicated
VVC
Diagnostic
Considerations in Uncomplicated VVC
A
diagnosis of Candida vaginitis is suggested clinically by
the presence of external dysuria and vulvar pruritis, pain,
swelling, and redness. Signs include vulvar edema, fissures,
excoriations, or thick curdy vaginal discharge. The diagnosis
can be made in a woman who has signs and symptoms of vaginitis
when either 1) a wet preparation (saline, 10% KOH) or Gram
stain of vaginal discharge demonstrates yeasts or pseudohyphae
or 2) a culture or other test yields a positive result for
a yeast species. Candida vaginitis is associated with a normal
vaginal pH (<4.5). Use of 10% KOH in wet preparations improves
the visualization of yeast and mycelia by disrupting cellular
material that might obscure the yeast or pseudohyphae. Examination
of a wet mount with KOH preparation should be performed for
all women with symptoms or signs of VVC, and women with a
positive result should receive treatment. For those with negative
wet mounts, vaginal cultures for Candida should be considered
for those with any sign or multiple symptoms. If Candida cultures
cannot be done, empiric treatment can be considered for symptomatic
women with any sign of VVC on examination when the wet mount
is negative. Identifying Candida by culture in the absence
of symptoms or signs is not an indication for treatment because
approximately 10%--20% of women harbor Candida sp. and other
yeasts in the vagina. VVC can occur concomitantly with STDs.
The majority of healthy women with uncomplicated VVC have
no identifiable precipitating factors.
Treatment
Short-course
topical formulations (i.e., single dose and regimens of 1--3
days) effectively treat uncomplicated VVC. The topically applied
azole drugs are more effective than nystatin. Treatment with
azoles results in relief of symptoms and negative cultures
in 80%--90% of patients who complete therapy.
Recommended
Regimens
Intravaginal Agents:
Butoconazole 2% cream 5 g intravaginally for 3 days*
OR
Butoconazole 2% cream 5 g (Butaconazole1-sustained release),
single intravaginal application
OR
Clotrimazole 1% cream 5 g intravaginally for 7--14 days*
OR
Clotrimazole 100 mg vaginal tablet for 7 days
OR
Clotrimazole 100 mg vaginal tablet, two tablets for 3 days
OR
Miconazole 2% cream 5 g intravaginally for 7 days*
OR
Miconazole 100 mg vaginal suppository, one suppository for
7 days*
OR
Miconazole 200 mg vaginal suppository, one suppository for
3 days*
OR
Miconazole 1,200 mg vaginal suppository, one suppository for
1 day*
OR
Nystatin 100,000-unit vaginal tablet, one tablet for 14 days
OR
Tioconazole 6.5% ointment 5 g intravaginally in a single application*
OR
Terconazole 0.4% cream 5 g intravaginally for 7 days
OR
Terconazole 0.8% cream 5 g intravaginally for 3 days
OR
Terconazole 80 mg vaginal suppository, one suppository for
3 days
Oral Agent:
Fluconazole 150 mg oral tablet, one tablet in single dose
*
Over-the-counter preparations.
The
creams and suppositories in this regimen are oil-based and
might weaken latex condoms and diaphragms. Refer to condom
product labeling for further information.
Intravaginal
preparations of butaconazole, clotrimazole, miconazole, and
tioconazole are available over-the-counter (OTC). Women whose
condition has previously been diagnosed with VVC are not necessarily
more likely to be able to diagnose themselves; therefore,
any woman whose symptoms persist after using an OTC preparation,
or who has a recurrence of symptoms within 2 months, should
be evaluated with office-based testing. Unnecessary or inappropriate
use of OTC preparations is common and can lead to a delay
in the treatment of other vulvovaginitis etiologies, which
can result in adverse clinical outcomes.
Follow-Up
Patients
should be instructed to return for follow-up visits only if
symptoms persist or recur within 2 months of onset of initial
symptoms.
Management of Sex Partners
VVC
is not usually acquired through sexual intercourse; treatment
of sex partners is not recommended but may be considered in
women who have recurrent infection. A minority of male sex
partners might have balanitis, which is characterized by erythematous
areas on the glans of the penis in conjunction with pruritus
or irritation. These men benefit from treatment with topical
antifungal agents to relieve symptoms.
Special
Considerations
Allergy,
Intolerance, and Adverse Reactions
Topical
agents usually cause no systemic side effects, although local
burning or irritation might occur. Oral agents occasionally
cause nausea, abdominal pain, and headache. Therapy with the
oral azoles has been associated rarely with abnormal elevations
of liver enzymes. Clinically important interactions can occur
when these oral agents are administered with other drugs,
including astemizole, calcium channel antagonists, cisapride,
coumadin, cyclosporin A, oral hypoglycemic agents, phenytoin,
protease inhibitors, tacrolimus, terfenadine, theophylline,
trimetrexate, and rifampin.
Complicated
VVC
Recurrent
Vulvovaginal Candidiasis (RVVC)
RVVC,
usually defined as four or more episodes of symptomatic VVC
in 1 year, affects a small percentage of women (<5%). The
pathogenesis of RVVC is poorly understood, and the majority
of women with RVVC have no apparent predisposing or underlying
conditions. Vaginal cultures should be obtained from patients
with RVVC to confirm the clinical diagnosis and to identify
unusual species, including nonalbicans species, particularly
Candida glabrata (C. glabrata does not form pseudohyphae or
hyphae and is not easily recognized on microscopy). C. glabrata
and other nonalbicans Candidia species are observed in 10%--20%
of patients with RVVC. Conventional antimycotic therapies
are not as effective against these species as against C. albicans.
Treatment
Each
individual episode of RVVC cause
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