Diseases Characterized by Vaginal Discharge
Most women will have a vaginal infection, characterized by discharge, itching, or odor, during their lifetime. With the availability of complementary and alternative therapies and over-the-counter medications for candidiasis, many symptomatic women seek these products before or in addition to an evaluation by a medical provider.
Obtaining a medical history alone has been shown to be insufficient for accurate diagnosis of vaginitis and can lead to the inappropriate administration of medication. Therefore, a careful history, examination, and laboratory testing to determine the etiology of vaginal complaints are warranted. Information on sexual behaviors and practices, gender of sex partners, menses, vaginal hygiene practices (such as douching), and other medications should be elicited. The three diseases most frequently associated with vaginal discharge are BV (caused by the replacement of the vaginal flora by an overgrowth of anaerobic bacteria including Prevotella sp., Mobiluncus sp., G. vaginalis, Ureaplasma, Mycoplasma, and numerous fastidious or uncultivated anaerobes) trichomoniasis (caused by T. vaginalis), and candidiasis (usually caused by Candida albicans). Cervicitis also 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 who have vaginal complaints or who are being evaluated for STDs.
Various diagnostic methods are available to identify the etiology of an abnormal vaginal discharge. Clinical laboratory testing can identify the cause of vaginitis in most women and is discussed in detail in the sections of this report dedicated to each condition. In the clinician’s office, the cause of vaginal symptoms might be determined by pH, a potassium hydroxide (KOH) test, 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. Because pH testing is not highly specific, discharge should be further examined microscopically by first diluting one sample in one to two drops of 0.9% normal saline solution on one slide and a second sample in 10% KOH solution (samples that emit an amine odor immediately upon application of KOH suggest BV or trichomoniasis infection). Cover slips are then placed on the slides, and they are examined under a microscope at low and high power.
The saline-solution specimen might yield motile T. vaginalis, or clue cells (i.e., epithelial cells with borders obscured by small bacteria), which are characteristic of BV, whereas the presence of WBCs without evidence of trichomonads or yeast in this solution is suggestive of cervicitis (see Cervicitis). The KOH specimen typically is used to identify the yeast or pseudohyphae of Candida species. However, the absence of trichomonads or pseudohyphae in KOH samples does not rule out these infections, because the sensitivity of microscropy is approximately 50% compared with NAAT (trichomoniasis) or culture (yeast).
In settings where pH paper, KOH, and microscopy are not available, alternative commercially available point-of-care tests or clinical laboratory testing can be used to diagnose vaginitis. The presence of objective signs of vulvar inflammation in the absence of vaginal pathogens after laboratory testing, along with a minimal amount of discharge, suggests the possibility of mechanical, chemical, allergic, or other noninfectious irritation of the vulva.
BV is a polymicrobial clinical syndrome resulting from replacement of the normal hydrogen peroxide producing Lactobacillus sp. in the vagina with high concentrations of anaerobic bacteria (e.g., Prevotella sp. and Mobiluncus sp.), G. vaginalis, Ureaplasma, Mycoplasma, and numerous fastidious or uncultivated anaerobes. Some women experience transient vaginal microbial changes, whereas others experience them for a longer intervals of time. Among women presenting for care, BV is the most prevalent cause of vaginal discharge or malodor; however, in a nationally representative survey, most women with BV were asymptomatic (318).
BV is associated with having multiple male or female partners, a new sex partner, douching, lack of condom use, and lack of vaginal lactobacilli; women who have never been sexually active can also be affected. The cause of the microbial alteration that characterizes BV is not fully understood, nor is whether BV results from acquisition of a sexually transmitted pathogen. Nonetheless, women with BV are at increased risk for the acquisition of some STDs (e.g., HIV, N. gonorrhoeae, C. trachomatis, and HSV- 2), complications after gynecologic surgery, complications of pregnancy, and recurrence of BV. Treatment of male sex partners has not been beneficial in preventing the recurrence of BV.
BV can be diagnosed by the use of clinical criteria (i.e., Amsel’s Diagnostic Criteria) (319) or Gram stain. A Gram stain (considered the gold standard laboratory method for diagnosing BV) is used to determine the relative concentration of lactobacilli (i.e., 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 (i.e., Mobiluncus) characteristic of BV. If a Gram stain is not available, clinical criteria can be used and 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; or
- a fishy odor of vaginal discharge before or after addition of 10% KOH (i.e., the whiff test).
Detection of three of these criteria has been correlated with results by Gram stain (320). Other tests, including a DNA probe-based test for high concentrations of G. vaginalis (Affirm VP III, Becton Dickinson, Sparks, Maryland), a prolineaminopeptidase test card (Pip Activity TestCard, Quidel, San Diego, California), and the OSOM BVBlue test have acceptable performance characteristics compared with Gram stain. Although a card test is available for the detection of elevated pH and trimethylamine, it has low sensitivity and specificity and therefore is not recommended. PCR also has been used in research settings for the detection of a variety of organisms associated with BV, but evaluation of its clinical utility is uncertain. Detection of one organism or group of organisms might be predictive of BV by Gram stain (321). However, additional evaluations are needed to confirm these associations. Culture of G. vaginalis is not recommended as a diagnostic tool because it is not specific. Cervical Pap tests have no clinical utility for the diagnosis of BV because of their low sensitivity.
Treatment is recommended for women with symptoms. The established benefits of therapy in nonpregnant women are to relieve vaginal symptoms and signs of infection. Other potential benefits to treatment include reduction in the risk for acquiring C. trachomatis or N. gonorrhoeae (322), HIV, and other viral STDs.
Metronidazole 500 mg orally twice a day for 7 days*
Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days
Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days†
* Consuming alcohol should be avoided during treatment 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).
Providers should consider patient preference, possible side-effects, drug interactions, and other coinfections when selecting a regimen. Women should be advised to refrain from intercourse or to use condoms consistently and correctly during the treatment regimen. Douching might increase the risk for relapse, and no data support the use of douching for treatment or relief of symptoms.
Tinidazole 2 g orally once daily for 2 days
Tinidazole 1 g orally once daily for 5 days
Clindamycin 300 mg orally twice daily for 7 days
Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
Alternative regimens include several tinidazole regimens (323) or clindamycin (oral or intravaginal) (324). Additional regimens include metronidazole (750-mg extended release tablets once daily for 7 days), or a single dose of clindamycin intravaginal cream, although data on the performance of these alternative regimens are limited.
Several studies have evaluated the clinical and microbiologic efficacy of using intravaginal lactobacillus formulations to treat BV and restore normal flora (325-327). Further research efforts to determine the role of these regimens in BV treatment and prevention are ongoing.
Follow-up visits are unnecessary if symptoms resolve. Because recurrence of BV is common, women should be advised to return for evaluation if symptoms recur. Detection of certain BV-associated organisms have been associated with antimicrobial resistance and might determine risk for subsequent treatment failure (328-333). Limited data are available regarding optimal management strategies for women with early treatment failure. Using a different treatment regimen might be an option in patients who have a recurrence; however, re-treatment with the same topical regimen is another acceptable approach for treating recurrent BV during the early stages of infection (334). For women with multiple recurrences after completion of a recommended regimen, metronidazole gel twice weekly for 4-6 months has been shown to reduce recurrences, although this benefit might not persist when suppressive therapy is discontinued (335). Limited data suggest that oral nitroimidazole followed by intravaginal boric acid and suppressive metronidazole gel for those women in remission might be an option in women with recurrent BV (336). Monthly oral metronidazole administered with fluconazole has also been evaluated as suppressive therapy (337).
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.
Allergy or Intolerance to the Recommended Therapy
Intravaginal clindamycin cream is preferred in case of allergy or intolerance to metronidazole or tinidazole. Intravaginal metronidazole gel can be considered for women who do not tolerate systemic metronidazole. Intravaginal metronidazole should not be administered to women allergic to metronidazole.
Treatment is recommended for all pregnant women with symptoms. Although BV is associated with adverse pregnancy outcomes, including premature rupture of membranes, preterm labor, preterm birth, intra-amniotic infection, and postpartum endometritis, the only established benefit of therapy for BV in pregnant women is the reduction of symptoms and signs of vaginal infection. Additional potential benefits include reducing the risk for infectious complications associated with BV during pregnancy and reducing the risk for other infections (other STDs or HIV).
Several trials have been undertaken to determine the efficacy of BV treatment among pregnant women. Two trials demonstrated that metronidazole was efficacious during pregnancy using the 250-mg regimen (338,339); however, metronidazole administered at 500 mg twice daily can be used. One trial involving a limited number of participants revealed that treatment with oral metronidazole 500 mg twice daily was equally effective as metronidazole gel, with cure rates of 70% using Amsel criteria to define cure (340), and a recent trial demonstrated a cure rate of 85% using Gram stain criteria after 4 weeks with oral clindamycin (341). Multiple studies and meta-analyses have not demonstrated an association between metronidazole use during pregnancy and teratogenic or mutagenic effects in newborns (342,343). Regardless of the antimicrobial agent used to treat pregnant women, oral therapy is preferred because of the possibility of subclinical upper-genital–tract infection.
Recommended Regimens for Pregnant Women
Metronidazole 500 mg orally twice a day for 7 days
Metronidazole 250 mg orally three times a day for 7 days
Clindamycin 300 mg orally twice a day for 7 days
Treatment of asymptomatic BV among pregnant women who are at high risk for preterm delivery (i.e., those with a previous preterm birth) has been evaluated by several studies, which have yielded mixed results. Seven trials have evaluated treatment of pregnant women with asymptomatic BV at high risk for preterm delivery; one showed harm (344), two showed no benefit (345,346), and four demonstrated benefit (338,339,347,348) . Therefore, evidence is insufficient to assess the impact of screening for BV in pregnant women at high risk for preterm delivery (85).
Similarly, data are inconsistent regarding whether the treatment of asymptomatic pregnant women with BV who are at low risk for preterm delivery reduces adverse outcomes of pregnancy. Although USPSTF recommends against screening these women (85), one trial demonstrated a 40% reduction in spontaneous preterm birth among women using oral clindamycin during weeks 13–22 of gestation (348). Several additional trials have shown that intravaginal clindamycin given at an average gestation of later than 20 weeks did not reduce preterm birth, and in three of these trials, intravaginal clindamycin cream administered at 16–32 weeks’ gestation was associated with an increase in adverse events (e.g., low birth weight and neonatal infections) in newborns (346,349-351). Providers should be aware that intravaginal clindamycin cream might be associated with adverse outcomes if used in the latter half of pregnancy.
BV appears to recur with higher frequency in HIV-positive women (352). Patients who have BV and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.
Trichomoniasis is caused by the protozoan T. vaginalis. Some men who are infected with T. vaginalis might not have symptoms; others have NGU. Some women have symptoms characterized by a diffuse, malodorous, yellow-green vaginal discharge with vulvar irritation. However, many women have minimal or no symptoms. Because of the high prevalence of trichomoniasis in clinical and nonclinical settings (64,92,353,354), testing for T. vaginalis should be performed in women seeking care for vaginal discharge. Screening for T. vaginalis in women can be considered in those at high risk for infection (i.e., women who have new or multiple partners, have a history of STDs, exchange sex for payment, and use injection drugs).
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. 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. Each of these tests, which are performed on vaginal secretions, have a sensitivity of >83% and a specificity of >97%. Both tests are considered point-of-care diagnostics. The results of the OSOM Trichomonas Rapid Test are available in approximately 10 minutes, whereas results of the Affirm VP III are available within 45 minutes. Although these tests tend to be more sensitive than those requiring vaginal wet preparation, false positives might occur, especially in populations with a low prevalence of disease.
Culture is another sensitive and highly specific commercially available method of diagnosis. Among women in whom trichomoniasis is suspected but not confirmed by microscopy, vaginal secretions should be cultured for T. vaginalis. While the sensitivity of a Pap test for T. vaginalis diagnosis is poor, use of a liquid-based testing has demonstrated enhanced sensitivity; however, false-positive tests can occur, and confirmatory testing might be needed in some circumstances (355). An FDA-cleared PCR assay for detection of gonorrhea and chlamydial infection (Amplicor, manufactured by Roche Diagnostic Corp.) has been modified for T. vaginalis detection in vaginal or endocervical swabs and in urine from women and men; sensitivity ranges from 88%–97% and specificity from 98%–99% (356). APTIMA T. vaginalis Analyte Specific Reagents (ASR; manufactured by Gen-Probe, Inc.) also can detect T. vaginalis RNA by transcription-mediated amplification using the same instrumentation platforms available for the FDA-cleared APTIMA Combo2 assay for diagnosis of gonorrhea and chlamydial infection; published validation studies of T. vaginalis ASR found sensitivity ranging from 74%–98% and specificity of 87%–98% (357-359). Laboratories that use the Gen-Probe APTIMA Combo2 test for detection of N. gonorrhoeae and C. trachomatis can consider adding the T. vaginalis ASR to their testing armentarium, as long as the necessary CLIA verification studies have been conducted.
In men, wet preparation is not a sensitive test, and no approved point-of-care tests are available. Culture testing of urethral swab, urine, or semen is one diagnostic option; however, NAATs (i.e., PCR or transcription-mediated amplification [TMA]) have superior sensitivity for T. vaginalis diagnosis in men (356,359). T. vaginalis has not been found to infect oral sites, and rectal prevalence appears low in MSM (360). Therefore, oral and rectal testing for T. vaginalis is not recommended.
Metronidazole 2 g orally in a single dose
Tinidazole 2 g orally in a single dose
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 or superior to metronidazole in achieving parasitologic cure and resolution of symptoms (361). 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 this gel is not recommended. Several other topically applied antimicrobials occasionally have been used for treatment of trichomoniasis; however, these preparations likely are no more effective than metronidazole gel.
Because of the high rate of reinfection among patients in whom trichomoniasis was diagnosed (17% were reinfected within 3 months in one study), rescreening for T. vaginalis at 3 months following initial infection can be considered for sexually active women with trichomoniasis; the benefit of this approach, however, has not been fully evaluated (64). No data support rescreening in men diagnosed with T. vaginalis. While most recurrent T. vaginalis infections are thought to result from having sex with an untreated partner (i.e., reinfection), some recurrent cases can be attributed to diminished susceptibility to metronidazole. Low-level metronidazole resistance has been identified in 2%–5% of cases of vaginal trichomoniasis (362,363), but high-level resistance only rarely occurs. Fortunately, infections caused by most of these organisms respond to tinidazole or higher doses of metronidazole. Tinidazole has a longer serum half-life and reaches higher levels in genitourinary tissues than metronidazole. In addition, many T. vaginalis isolates have lower minimal lethal concentrations (MLCs) 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. For patients failing this regimen, treatment with tinidazole or metronidazole at 2 g orally for 5 days should be considered. 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: 404-718-4141; 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 abstain from sex until they and their sex partners are cured (i.e., when therapy has been completed and patient and partner[s] are asymptomatic). Existing data suggest that patient-delivered partner therapy might have a role in partner management for trichomoniasis; however, no one partner management intervention has shown superiority over another in reducing reinfection rates (72,73). Although no data are available to guide treatment of the male partners of women with nitroimidazole treatment failure, on the basis of expert opinion, male partners should be evaluated and treated with either tinidazole in a single dose of 2 g orally or metronidazole twice a day at 500 mg orally for 7 days.
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 (364-366). Topical therapy with drugs other than nitroimidazoles can be attempted, but cure rates are low (<50%).
Vaginal trichomoniasis has been associated with adverse pregnancy outcomes, particularly premature rupture of membranes, preterm delivery, and low birth weight. However, metronidazole treatment has not been shown to reduce perinatal morbidity. Although some trials suggest the possibility of increased prematurity or low birth weight after metronidazole treatment, limitations of the studies prevent definitive conclusions regarding risks for treatment (367,368). 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 and communicate the option of therapy deferral in asymptomatic pregnant women until after 37 weeks’ gestation. All symptomatic pregnant women should not only be considered for treatment regardless of pregnancy stage, but be provided careful counseling regarding condom use and the continued risk of sexual transmission.
Women can be treated with 2 g metronidazole in a single dose at any stage of pregnancy. Multiple studies and meta-analyses have not demonstrated an association between metronidazole use during pregnancy and teratogenic or mutagenic effects in infants (342,343,369). The safety of tinidazole in pregnant women, however, 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 the infant to metronidazole. For women treated with tinidazole, interruption of breastfeeding is recommended during treatment and for 3 days after the last dose.
There is increasing evidence for epidemiologic and biologic interaction between HIV and T. vaginalis (370-375). T. vaginalis infection in HIV-infected women might enhance HIV transmission by increasing genital shedding of the virus (376,377), and treatment for T. vaginalis has been shown to reduce HIV shedding (376,377). For sexually active women who are HIV-positive, screening for trichomoniasis at entry into care with subsequent screening performed at least annually is recommended based on the reported prevalence of T. vaginalis, the effect of treatment at reducing vaginal HIV shedding, and the potential complications of upper-genital-tract infections among women who are left untreated (130,370-375). Rescreening 3 months after completion of therapy should be considered among HIV-positive women with trichomoniasis, a recommendation based on the high proportion of recurrent or persistent infection and the association between HIV and T. vaginalis infection (64,374,378).
A recent randomized clinical trial involving women coinfected with trichomoniasis and HIV demonstrated that a single dose of metronidazole 2 gm orally was not as effective as 500 mg twice daily for 7 days (379). Therefore, a multi-dose treatment regimen for T. vaginalis can be considered in HIV-infected women.
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 within their lifetime. On the basis of clinical presentation, microbiology, host factors, and response to therapy, VVC can be classified as either uncomplicated or complicated (Box 3). Approximately 10%–20% of women will have complicated VVC that necessitates diagnostic and therapeutic considerations.
A diagnosis of Candida vaginitis is suggested clinically by the presence of external dysuria and vulvar pruritus, 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, hyphae, or pseudohyphae or 2) a culture or other test yields a yeast species. Candida vaginitis is associated with a normal vaginal pH (<4.5), and therefore, pH testing is not a useful diagnostic tool. 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 women with negative wet mounts who are symptomatic, vaginal cultures for Candida should be considered. If the wet mount is negative and Candida cultures cannot be done, empiric treatment can be considered for symptomatic women with any sign of VVC on examination. 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. Most healthy women with uncomplicated VVC have no identifiable precipitating factors.
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.
Over-the-Counter Intravaginal Agents:
Butoconazole 2% cream 5 g intravaginally for 3 days
Clotrimazole 1% cream 5 g intravaginally for 7–14 days
Clotrimazole 2% cream 5 g intravaginally for 3 days
Miconazole 2% cream 5 g intravaginally for 7 days
Miconazole 4% cream 5 g intravaginally for 3 days
Miconazole 100 mg vaginal suppository, one suppository for 7 days
Miconazole 200 mg vaginal suppository, one suppository for 3 days
Miconazole 1,200 mg vaginal suppository, one suppository for 1 day
Tioconazole 6.5% ointment 5 g intravaginally in a single application
Prescription Intravaginal Agents:
Butoconazole 2% cream (single dose bioadhesive product), 5 g intravaginally for 1 day
Nystatin 100,000-unit vaginal tablet, one tablet for 14 days
Terconazole 0.4% cream 5 g intravaginally for 7 days
Terconazole 0.8% cream 5 g intravaginally for 3 days
Terconazole 80 mg vaginal suppository, one suppository for 3 days
Fluconazole 150 mg oral tablet, one tablet in single dose
The creams and suppositories in this regimen are oil-based and might weaken latex condoms and diaphragms. Patients and providers should 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 capable of diagnosing 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.
Box 3. Classification of vulvovaginal candidiasis (VVC)
- Sporadic or infrequent vulvovaginal candidiasis
- Mild-to-moderate vulvovaginal candidiasis
- Likely to be C. albicans
- Non-immunocompromised women
- Recurrent vulvovaginal candidiasis
- Severe vulvovaginal candidiasis
- Non-albicans candidiasis
- Women with uncontrolled diabetes, debilitation, or immunosuppression
Patients should be instructed to return for follow-up visits only if symptoms persist or recur within 2 months of onset of the initial symptoms.
Management of Sex Partners
VVC is not usually acquired through sexual intercourse; no data support the treatment of sex partners. 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.
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, cyclosporin A, oral hypoglycemic agents, phenytoin, protease inhibitors, tacrolimus, terfenadine, theophylline, trimetrexate, rifampin, and warfarin.
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 most 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. Although C. glabrata and other nonalbicans Candidia species are observed in 10%–20% of patients with RVVC, C. glabrata does not form pseudohyphae or hyphae and is not easily recognized on microscopy. Conventional antimycotic therapies are not as effective against these species as they are against C. albicans.
Each individual episode of RVVC caused by C. albicans responds well to short-duration oral or topical azole therapy. However, to maintain clinical and mycologic control, some specialists recommend a longer duration of initial therapy (e.g., 7–14 days of topical therapy or a 100-mg, 150-mg, or 200-mg oral dose of fluconazole every third day for a total of 3 doses [day 1, 4, and 7]) to attempt mycologic remission before initiating a maintenance antifungal regimen.
Oral fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months is the first line of treatment. If this regimen is not feasible, topical treatments used intermittently as a maintenance regimen can be considered. Suppressive maintenance antifungal therapies are effective in reducing RVVC. However, 30%–50% of women will have recurrent disease after maintenance therapy is discontinued. Routine treatment of sex partners is controversial. C. albicans azole resistance is rare in vaginal isolates, and susceptibility testing is usually not warranted for individual treatment guidance.
Severe vulvovaginitis (i.e., extensive vulvar erythema, edema, excoriation, and fissure formation) is associated with lower clinical response rates in patients treated with short courses of topical or oral therapy. Either 7–14 days of topical azole or 150 mg of fluconazole in two sequential doses (second dose 72 hours after initial dose) is recommended.
The optimal treatment of nonalbicans VVC remains unknown. Options include longer duration of therapy (7–14 days) with a nonfluconazole azole drug (oral or topical) as first-line therapy. If recurrence occurs, 600 mg of boric acid in a gelatin capsule is recommended, administered vaginally once daily for 2 weeks. This regimen has clinical and mycologic eradication rates of approximately 70% (380). If symptoms recur, referral to a specialist is advised.
Women with underlying debilitating medical conditions (e.g., those with uncontrolled diabetes or those receiving corticosteroid treatment) do not respond as well to short-term therapies. Efforts to correct modifiable conditions should be made, and more prolonged (i.e., 7–14 days) conventional antimycotic treatment is necessary.
VVC frequently occurs during pregnancy. Only topical azole therapies, applied for 7 days, are recommended for use among pregnant women.
The incidence of VVC in HIV-infected women is unknown. Vaginal Candida colonization rates among HIV-infected women are higher than among those for seronegative women with similar demographic characteristics and high-risk behaviors, and the colonization rates correlate with increasing severity of immunosuppression. Symptomatic VVC is more frequent in seropositive women and similarly correlates with severity of immunodeficiency. In addition, among HIV-infected women, systemic azole exposure is associated with the isolation of nonalbicans Candida species from the vagina.
On the basis of available data, therapy for VVC in HIV-infected women should not differ from that for seronegative women. Although long-term prophylactic therapy with fluconazole at a dose of 200 mg weekly has been effective in reducing C. albicans colonization and symptomatic VVC (381), this regimen is not recommended for routine primary prophylaxis in HIV-infected women in the absence of recurrent VVC (129). Given the frequency at which RVVC occurs in the immmunocompetent healthy population, the occurrence of RVVC should not be considered an indication for HIV testing among women previously testing HIV negative. Although VVC is associated with increased HIV seroconversion in HIV-negative women and increased HIV cervicovaginal levels in HIV-positive women, the effect of treatment for VVC on HIV acquisition and transmission remains unknown.