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This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:

• STD Treatment Guidelines   at http://www.cdc.gov/STD/treatment

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1993 Sexually Transmitted Diseases Treatment Guidelines

09/24/1993

SUGGESTED CITATION
Centers for Disease Control and Prevention. 1993 Sexually
transmitted diseases treatment guidelines. MMWR 1993;42(No. RR-14):
{inclusive page numbers}.

CIO Responsible for this publication:
National Center for Prevention Services,
Division of Sexually Transmitted Diseases and HIV Prevention

DISEASES CHARACTERIZED BY VAGINAL DISCHARGE

Management of the Patient with Vaginitis
     
     Vaginitis is characterized by a vaginal discharge (usually) or
vulvar itching and irritation; a vaginal odor may be present. The
three common diseases characterized by vaginitis include
trichomoniasis (caused by T. vaginalis), BV (caused by a
replacement of the normal vaginal flora by an overgrowth of
anaerobic microorganisms and Gardnerella vaginalis), and
candidiasis (usually caused by Candida albicans). MPC caused by C.
trachomatis or N. gonorrhoeae may uncommonly cause a vaginal
discharge. Although vulvovaginal candidiasis is not usually
transmitted sexually, it is included here because it is a common
infection among women being evaluated for STDs.

     The diagnosis of vaginitis is made 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 for
the elevated pH (greater than 4.5) typical of BV or trichomoniasis.
One way to examine the discharge is to dilute a sample in 1-2 drops
of 0.9% normal saline solution on one slide and 10% potassium
hydroxide (KOH) solution on a second slide. An amine odor detected
immediately after applying KOH suggests either BV or
trichomoniasis. A cover slip is placed on each slide and they are
examined under a microscope at low- and high-dry power. The motile
T. vaginalis or the clue cells of BV are usually easily identified
in the saline specimen. The yeast or pseudohyphae of Candida
species are more easily identified in the KOH specimen. 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 or chemical irritation of
the vulva. Culture for T. vaginalis or Candida species is more
sensitive than microscopic examination, but the specificity of
culture for Candida species to diagnose vaginitis is less clear.
Laboratory testing fails to identify a cause among a substantial
minority of women.

Bacterial Vaginosis
     
     BV is a clinical syndrome resulting from replacement of the
normal H2O2-producing Lactobacillus spp in the vagina with high
concentrations of anaerobic bacteria (e.g., Bacteroides spp,
Mobiluncus spp), G. vaginalis, and Mycoplasma hominis. This
condition is the most prevalent cause of vaginal discharge or
malodor. However, half the women who meet clinical criteria for BV
have no symptoms. The cause of the microbial alteration is not
fully understood. Although BV is associated with sexual activity in
that women who have never been sexually active are rarely affected
and acquisition of BV is associated with having multiple sex
partners, BV is not considered exclusively an STD. Treatment of the
male sex partner has not been found beneficial in preventing the
recurrence of BV.

Diagnostic Considerations
     BV may be diagnosed by the use of clinical or Gram stain
criteria. Clinical criteria require three of the following symptoms
or signs:

--   A homogeneous, white, noninflammatory discharge that adheres
     to the vaginal walls;

--   The presence of clue cells on microscopic examination;

--   pH of vaginal fluid greater than 4.5;

--   A fishy odor of vaginal discharge before or after addition of
     10% KOH (whiff test).

     When Gram stain is used, determining the relative
concentration of the bacterial morphotypes characteristic of the
altered flora of BV is an acceptable laboratory method for
diagnosing BV. Culture of G. vaginalis is not recommended as a
diagnostic tool because it is not specific. G. vaginalis can be
isolated from vaginal cultures among half of normal women.

Treatment
     The principal goal of therapy is to relieve vaginal symptoms
and signs. Therefore, only women with symptomatic disease require
treatment. Because male sex partners of women with BV are not
symptomatic, and because treatment of male partners has not been
shown to alter either the clinical course of BV in women during
treatment or the relapse/reinfection rate, preventing transmission
to men is not a goal of therapy.

     Many bacterial flora characterizing BV have been recovered
from the endometrium or salpinx of women with PID. BV has been
associated with endometritis, PID, or vaginal cuff cellulitis
following invasive procedures such as endometrial biopsy,
hysterectomy, hysterosalpingography, placement of IUD, caesarian
section, or uterine curettage. A randomized controlled trial found
that treatment of BV with metronidazole substantially reduced
post-abortion PID. Based on these data, it may be reasonable to
consider treatment of BV (symptomatic or asymptomatic) before
performing surgical abortion procedures. However, more data are
needed to consider treatment of asymptomatic patients with BV when
performing other invasive procedures.

Recommended Regimen -
     Metronidazole 500 mg orally 2 times a day for 7 days.

NOTE: Patients should be advised to avoid using alcohol during
treatment with metronidazole and for 24 hours thereafter.
Alternative Regimens

     Metronidazole 2 g orally in a single dose.

     The following alternative regimens have been effective in
clinical trials, although experience with these regimens is
limited.

     Clindamycin cream, 2%, one full applicator (5 g)
     intravaginally at bedtime for 7 days;
                           or
     Metronidazole gel, 0.75%, one full applicator (5 g)
     intravaginally, 2 times a day for 5 days;
                           or
     Clindamycin 300 mg orally 2 times a day for 7 days.

     Oral metronidazole has been shown in numerous studies to be
efficacious for the treatment of BV, resulting in relief of
symptoms and improvement in clinical course and flora disturbances.
Based on efficacy data from four randomized-controlled trials, the
overall cure rates are 95% for the 7-day regimen and 84% for the 2
g single-dose regimen.

     Some health-care providers remain concerned about the
possibility of metronidazole mutagenicity, which has been suggested
by experiments on animals using extremely high and prolonged doses.
However, there is no evidence for mutagenicity in humans. Some
health-care providers prefer the intravaginal route because of lack
of systemic side effects such as mild-to-moderate gastrointestinal
upset and unpleasant taste (mean peak serum concentrations of
metronidazole following intravaginal administration are less than
2% those of standard 500 mg oral doses and mean bioavailability of
clindamycin cream is about 4%).

Follow-Up
     Follow-up visits are not necessary if symptoms resolve.
Recurrence of BV is common. The alternative treatment regimens
suitable for BV treatment may be used for treatment of recurrent
disease. No long-term maintenance regimen with any therapeutic
agent is currently available.

Management of Sex Partners
     Treatment of sex partners in clinical trials has not
influenced the woman's response to therapy, nor has it influenced
the relapse or recurrence rate. Therefore, routine treatment of sex
partners is not recommended.

Special Considerations

Allergy or Intolerance to the Recommended Therapy
     Clindamycin cream is preferred in case of allergy or
intolerance to metronidazole. Metronidazole gel can be considered
for patients who do not tolerate systemic metronidazole, but
patients allergic to oral metronidazole should not be administered
metronidazole vaginally.

Pregnancy -
     Because metronidazole is contraindicated during the first
trimester of pregnancy, clindamycin vaginal cream is the preferred
treatment for BV during the first trimester of pregnancy
(clindamycin cream is recommended instead of oral clindamycin
because of the general desire to limit the exposure of the fetus to
medication). During the second and third trimesters of pregnancy,
oral metronidazole can be used, although the vaginal metronidazole
gel or clindamycin cream may be preferable.

     BV has been associated with adverse outcomes of pregnancy
(e.g., premature rupture of the membranes, preterm labor, preterm
delivery), and the organisms found in increased concentration in BV
are also commonly present in postpartum or post-caesarean
endometritis. Whether treatment of BV among pregnant women would
reduce the risk of adverse pregnancy outcomes is unknown;
randomized controlled trials have not been conducted.

HIV infection -
     Persons with HIV and BV should receive the same treatment as
persons without HIV.


Trichomoniasis
     
     Trichomoniasis is caused by the protozoan T. vaginalis. The
majority of men infected with T. vaginalis are asymptomatic, but
many women are symptomatic. Among women, T. vaginalis typically
causes a diffuse, malodorous, yellow-green discharge with vulvar
irritation. There is recent evidence of a possible relationship
between vaginal trichomoniasis and adverse pregnancy outcomes,
particularly premature rupture of the membranes and preterm
delivery.

Recommended Regimen -
     Metronidazole 2 g orally in a single dose.

Alternative Regimen -
     Metronidazole 500 mg twice daily for 7 days.

     Only metronidazole is available in the United States for the
treatment of trichomoniasis. In randomized clinical trials, both of
the recommended metronidazole regimens have resulted in cure rates
of approximately 95%. Treatment of the patient and sex partner
results in relief of symptoms, microbiologic cure, and reduction of
transmission. Metronidazole gel has been approved for the treatment
of BV but it has not been studied for the treatment of
trichomoniasis. Earlier preparations of metronidazole for topical
vaginal therapy demonstrated low efficacy against trichomoniasis.

Follow-Up
     Follow-up is unnecessary for men and for women who become
asymptomatic after treatment.

     Infections by strains of T. vaginalis with diminished
susceptibility to metronidazole occur. However, most of these
organisms respond to higher doses of metronidazole. If failure
occurs with either regimen, the patient should be retreated with
metronidazole 500 mg 2 times a day for 7 days. If repeated failure
occurs, the patient should be treated with a single 2 g dose of
metronidazole once daily for 3-5 days.

     Patients with culture-documented infection who do not respond
to the regimens described in this report and in whom reinfection
has been excluded, should be managed in consultation with an
expert. Evaluation of such cases should include determination of
the susceptibility of T. vaginalis to metronidazole.

Management of Sex Partners
     Sex partners should be treated. Patients should be instructed
to avoid sex until patient and partner(s) are cured. In the absence
of microbiologic test-of-cure, this means when therapy has been
completed and patient and partner(s) are without symptoms.

Special Considerations

Allergy, Intolerance, or Adverse Reactions
     Effective alternatives to therapy with metronidazole are not
available.

Pregnancy -
     The use of metronidazole is contraindicated in the first
trimester of pregnancy. Patients may be treated after the first
trimester with 2 g of metronidazole in a single dose.

HIV Infection -
     Persons with HIV infection and trichomoniasis should receive
the same treatment as persons without HIV.

Vulvovaginal Candidiasis
     
     Vulvovaginal candidiasis (VVC) is caused by C. albicans or,
occasionally, by other Candida spp, Torulopsis sp, or other yeasts.
An estimated 75% of women will experience at least one episode of
VVC during their lifetime, and 40%-45% will experience two or more
episodes. A small percentage of women (probably less than 5%)
experience recurrent VVC (RVVC). Typical symptoms of VVC include
pruritus and vaginal discharge. Other symptoms may include vaginal
soreness, vulvar burning, dyspareunia, and external dysuria. None
of these symptoms is specific for VVC. VVC usually is not sexually
acquired or transmitted.

Diagnostic Considerations
     A diagnosis of Candida vaginitis is suggested clinically by
pruritus in the vulvar area together with erythema of the vagina or
vulva; a white discharge may occur. The diagnosis can be made when
a woman has signs and symptoms of vaginitis, and when a wet
preparation or Gram stain of vaginal discharge demonstrates yeasts
or pseudohyphae, or when a culture or other test yields a positive
result for a yeast species. Vaginitis solely because of Candida
infection is associated with a normal vaginal pH ( less than or
equal to 4.5). Use of 10% KOH in wet preparations improves the
visualization of yeast and mycelia by disrupting cellular material
that may obscure the yeast or pseudohyphae. Identifying Candida in
the absence of symptoms should not lead to treatment, because
approximately 10%-20% of women normally harbor Candida spp and
other yeasts in the vagina. VVC may be present concurrently with
STDs.

Treatment
     Topical formulations provide effective treatment for VVC. The
topically applied azole drugs are more effective than nystatin.
Treatment with azoles results in relief of symptoms and negative
cultures among 80%-90% of patients after therapy is completed.

Recommended Regimens -
     The following intravaginal formulations are recommended for
the treatment of VVC.

     Butoconazole 2% cream 5 g intravaginally for 3 days;*
                            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
     Clotrimazole 500 mg vaginal tablet, one tablet single
     application;
                            or
     Miconazole 2% cream 5 g intravaginally for 7 days;* **
                            or
     Miconazole 200 mg vaginal suppository, one suppository for 3
     days;*
                            or
     Miconazole 100 mg vaginal suppository, one suppository for 7
     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 suppository, 1 suppository for 3 days.*

     Although information is not conclusive, single-dose treatments
should probably be reserved for cases of uncomplicated
mild-to-moderate VVC. Multi-day regimens (3- and 7-day) are the
preferred treatment for severe or complicated VVC.

     Preparations for intravaginal administration of both
miconazole and clotrimazole are now available over-the-counter (OTC
{nonprescription}), and women with VVC can choose one of those
preparations. The duration for treatment with either preparation is
7 days. Self-medication with OTC preparations should be advised
only for women who have been diagnosed previously with VVC and who
experience a recurrence of the same symptoms. Any woman whose
symptoms persist after using an OTC preparation or who experiences
a recurrence of symptoms within 2 months should seek medical care.

* These creams and suppositories are oil-based and may weaken latex
condoms and diaphragms. Refer to product labeling for further
information.

** Over-the-counter (OTC) preparations.

Alternative Regimens
     Several trials have demonstrated that oral azole agents such
as fluconazole, ketoconazole, and itraconazole may be as effective
as topical agents. The optimum dose and duration of oral therapy
have not been established, but a range of 1-5 days of treatment,
depending on the agent, has been effective in clinical trials. The
ease of administration of oral agents is an advantage over topical
therapies. However, the potential for toxicity associated with
using a systemic drug, particularly ketoconazole, must be
considered. No oral agent is approved currently by the FDA for the
treatment of acute VVC.

Follow-Up
     Patients should be instructed to return for follow-up visits
only if symptoms persist or recur. Women who experience three or
more episodes of VVC per year should be evaluated for predisposing
conditions (see Recurrent Vulvovaginal Candidiasis).

Management of Sex Partners
     VVC is not acquired through sexual intercourse; treatment of
sex partners has not been demonstrated to reduce the frequency of
recurrences. Therefore, routine notification or treatment of sex
partners is not warranted. A minority of male sex partners may have
balanitis, which is characterized by erythematous areas on the
glans in conjunction with pruritus or irritation. These partners
may benefit from treatment with topical antifungal agents to
relieve symptoms.

Special Considerations

Allergy or Intolerance to the Recommended Therapy
     Topical agents are usually free of systemic side effects,
although local burning or irritation may occur. Oral agents
occasionally cause nausea, abdominal pain, and headaches. Therapy
with the oral azoles has been associated rarely with abnormal
elevations of liver enzymes. Hepatotoxicity secondary to
ketoconazole therapy has been estimated to appear in 1:10,000 to
1:15,000 exposed persons. Clinically important interactions may
occur when these oral agents are administered with other drugs,
including terfenadine, rifampin, astemizole, phenytoin, cyclosporin
A, coumarin-like agents, or oral hypoglycemic agents.

Pregnancy -
     VVC is common during pregnancy. Only topical azole therapies
should be used for the treatment of pregnant women. The most
effective treatments that have been studied for pregnant women are
clotrimazole, miconazole, butoconazole, and terconazole. Many
experts recommend 7 days of therapy during pregnancy.

HIV Infection -
     Acute VVC occurs frequently among women with HIV infection and
may be more severe for these women than for other women. However,
insufficient information exists to determine the optimal management
of VVC in HIV-infected women. Until such information becomes
available, women with HIV infection and acute VVC should be treated
following the same regimens as for women without HIV infection.


Recurrent Vulvovaginal Candidiasis
     
     RVVC, usually defined as three or more episodes of symptomatic
VVC annually, affects a small proportion of women (probably less
than 5%). The natural history and pathogenesis of RVVC are poorly
understood. Risk factors for RVVC include diabetes mellitus,
immunosuppression, broad spectrum antibiotic use, corticosteroid
use, and HIV infection, although the majority of women with RVVC
have no apparent predisposing conditions. Clinical trials
addressing the management of RVVC have involved continuing therapy
between episodes.

Treatment
     The optimal treatment for RVVC has not been established.
Ketoconazole 100 mg orally, once daily for up to 6 months reduces
the frequency of episodes of RVVC. Current studies are evaluating
weekly intravaginal administration of clotrimazole, as well as oral
therapy with itraconazole and fluconazole, in the treatment of
RVVC. All cases of RVVC should be confirmed by culture before
maintenance therapy is initiated.

     Although patients with RVVC should be evaluated for
predisposing conditions, routinely performing HIV testing for women
with RVVC who do not have HIV risk factors is unwarranted.

Follow-Up
     Patients who are receiving treatment for RVVC should receive
regular follow-up to monitor the effectiveness of therapy and the
occurrence of side effects.

Management of Sex Partners
     Treatment of sex partners does not prevent recurrences, and
routine therapy is not warranted. However, partners with
symptomatic balanitis or penile dermatitis should be treated with
a topical agent.

Special Considerations

HIV Infection -
     Insufficient information exists to determine the optimal
management of RVVC among HIV-infected women. Until such information
becomes available, management should be the same as for other women
with RVVC.

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