Diagnosis and Treatment of Vulvovaginal Candidiasis

CLINICAL ACTIONS:

Vulvovaginal candidiasis (VVC) presents with symptoms of itching, redness and discharge. Recurrent VVC (RVVC) is diagnosed when women have ≥4 episodes of VVC within 12 months.

• Focus on the following when obtaining the history
  • Location | Duration | Relation to menses | Response to prior treatment and self-treatment | Sexual partners | Contraception
  • Note: Self-diagnosis and telephone diagnosis are unreliable
• Physical exam includes examination of vulva and vaginal vault
  • Signs of inflammation | Ulcers | Excoriation
• Diagnosis
  • Blastospores or pseudohyphae on saline or 10% KOH microscopy or
  • Positive culture in the presence of symptoms suggestive of candidiasis and negative microscopy

Note: Sensitivity of microscopy is only 50% to 70% and many cases will go undetected | False negative work-up more likely if patient has self-treated with OTC medications | Newer FDA approved commercial tests have higher sensitivities and “may prove to be useful”

Classification

Classify as uncomplicated or complicated

• Uncomplicated
  • Sporadic or infrequent
  • Candida albicans infection (suspected or proven)
  • Non-immunocompromised
  • Mild/ moderate symptoms and findings
• Complicated
  • Recurrent: ≥4 infections in 12 months
  • Severe symptoms and findings
  • Non-Albicans Candida (NAC)
  • Immunocompromised, including
    • Diabetes | Immunosuppression meds | HIV

SYNOPSIS:

VVC is a common clinical condition with most infections due to C. albicans. Uncomplicated infections respond promptly to 1-,3- and 7- day treatment options (see below).  Complicated/recurrent VVC may require longer duration of treatment and higher doses of medication.  NAC subtypes may be resistant to typical treatment.

KEY POINTS:

• Candida albicans is the most common cause of VVC
• NAC
  • Accounts for an increasing number of cases
  • NAC species include
    • glabrata | C. tropicalis | C. krusei | C. parapsilosis | C. guilliermondii
  • Correct identification is important as NACs have resistance/decreased susceptibilities to commonly used treatment

Treatment

Uncomplicated

• One-day therapy
  • Butoconazole 2% sustained-release cream intravaginally 5 g or
  • Fluconazole 150 mg po (Note – only oral agent) or
  • Miconazole 1,200 mg vaginal suppository or
  • Tioconazole 6.5% ointment 5 gram intravaginally
• 3-day therapy
  • Clotrimazole 2% cream 5 g daily intravaginally or
  • Miconazole 200 mg vaginal suppository daily or
  • Miconazole 4% cream 5 g intravaginally daily or
  • Terconazole 0.8% cream 5 gm intravaginally daily  or
  • Terconazole 80 mg vaginal suppository daily
• 7-day therapy
  • Clotrimazole 1% cream 5 g intravaginally daily or
  • Miconazole 2% cream 5 g intravaginally daily or
  • Miconazole 100 mg vaginal suppository
  • Terconazole 0.4% cream 5g intravaginally daily

Complicated 

• Fluconazole “is an effective and convenient treatment”

Recurrence (Candida albicans)

• Intensive therapy for 7–14 days
• Followed by prolonged treatment with fluconazole (first line)
  • Fluconazole 150 mg weekly for 6 months
• Acceptable alternative prolonged therapy (second line) if patient does not want or cannot tolerate fluconazole
  • Clotrimazole 500 mg weekly or
  • Clotrimazole 200 mg twice a week

Severe Infection (erosions, fissures, edema)

• Acute infection
  • Topical intravaginal azoles for 10 to 14 days or
  • Oral fluconazole every 3 days (day 1, 4 and 7)

If NAC confirmed

• Approximately 50% of patients may respond to topical imidazole treatment
• If unresponsive to topical imidazole treatment use
  • Boric acid 600 mg vaginal capsules daily x 14 days (minimum)
• If unresponsive patient, should be referred to a subspecialist

Pregnancy

• Only topical azole therapies for 7 days are recommended (CDC)

Note: The CDC states “Epidemiologic studies indicate a single 150-mg dose of fluconazole might be associated with spontaneous abortion and congenital anomalies; therefore, it should not be used”

Other treatments

• Data on the efficacy of the following are currently inconclusive
  • Probiotics | Yogurt | Garlic | Tea tree oil | Low carb diet | Depot medroxyprogesterone | Douching

Learn More – Primary Sources:

ACOG Practice Bulletin 215: Vaginitis in Nonpregnant Patients

An Update on the Roles of Non-albicans Candida Species in Vulvovaginitis

Recurrent Vulvovaginitis

BMJ Clinical Evidence: Candidiasis (vulvovaginal)

CDC STI Treatment Guidelines 2021: Vulvovaginal Candidiasis

BMJ: Recurrent vulvovaginal candidiasis

Are Vaginal Antimycotics Associated with an Increased Risk for Miscarriage?

BACKGROUND AND PURPOSE:

• Vulvovaginal candidiasis (VVC) may occur in more than 20% of pregnant women
• A previous study suggested an increased risk of miscarriage after the use of vaginal-antimycotic agents for vulvovaginal candidiasis
• Daniel et al. (AJOG, 2018) examined whether risk for spontaneous abortions is increased following first-trimester exposure to vaginal antimycotics

METHODS:

• Population-based retrospective cohort study
• Participants: All clinically apparent pregnancies admitted for birth or spontaneous abortion
• A computerized database of medication dispensation was linked with computerized databases containing information on births and spontaneous abortion
• Time-varying Cox regression models, adjusted for confounding variables such as mother’s age, hypothyroidism, diabetes mellitus, hypercoagulable or inflammatory conditions, recurrent miscarriage, IUD, ethnicity, tobacco use and the year of admission were used to assess the association

RESULTS:

• 65,457 pregnancies were included in the study
  • 58,949 (90.1%) ended with birth
  • 6,508 (9.9%) ended with spontaneous abortion
• Overall, 5% of pregnancies were exposed to vaginal antimycotic medications until the 20^th gestational week
  • 4.2% were exposed to clotrimazol
  • 1% were exposed to miconazole
• Exposure to vaginal antimycotics was not associated with spontaneous abortions as a group
  • Crude hazard ratio (HR) 1.11; 95% CI, 0.96–1.29
  • adjusted HR 1.11; 95% CI, 0.96–1.29
• Clotrimazole was not associated with increased risk
  • adjusted HR 1.05; 95% CI, 0.89–1.25
• Miconazole was also not associated with increased risk
  • adjusted HR 1.34; 95% CI, 0.99–1.80
• Dosage did not impact the findings

CONCLUSION:

• This study found no evidence that taking antimycotics (clotrimazole and miconazole) during the first trimester is associated with increased risk for miscarriage

Learn More – Primary Sources:

Vaginal antimycotics and the risk for spontaneous abortions

FDA Reviews Fluconazole in Pregnancy

SUMMARY:

Following a Danish study in 2016 by Nielsen et al. (JAMA, 2016), which concluded that fluconazole was associated with miscarriage, the FDA undertook a review to determine the safety of fluconazole in pregnancy. The FDA concluded (October 2019) that 

Based on our reviews of several studies, FDA has determined that the available data do not provide conclusive evidence of an increased risk of miscarriage or stillbirth with a single 150 mg dose of oral fluconazole (Diflucan)

We reviewed the 2016 study cited in this DSC and four additional epidemiological studies

We approved updated prescribing information in 2018 to include all available information on the use of fluconazole in women who are pregnant or breastfeeding

It adequately addresses the potential risk of harm to unborn babies

•  

CDC 2015 Sexually Transmitted Diseases Treatment Guidelines: Vulvovaginal Candidiasis

Vulvovaginal candidiasis occurs frequently during pregnancy. Only topical azole therapies, applied for 7 days, are recommended for use among pregnant women

• Imidazoles inhibit the enzyme that converts lanosterol to ergosterol, disrupting the structure and function of the fungal membrane
• Azole options can be found below in the ObG Related Entry ‘Diagnosis and Treatment of Vulvovaginal Candidiasis’ 

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Learn More – Primary Sources:

ACOG Practice Bulletin 215: Vaginitis in Nonpregnant Patients 

Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth

Use of oral fluconazole during pregnancy and the risk of birth defects

Exposure to fluconazole and risk of congenital malformations in the offspring: A systematic review and meta-analysis 

Fluconazole use and birth defects in the National Birth Defects Prevention Study

Screening & Treatment of Gynecologic infections in the HIV-Positive Woman

Gynecologic infections are more common, and may be more difficult to eradicate, in the HIV population.  Overall, treatment protocols remain the same, irrespective of HIV status, although there are some differences depending on the disorder.

CLINICAL ACTIONS:

• Screen at entry to care and at least annually for the following: N. gonorrhoeae, C. trachomatis, syphilis and vaginal trichomoniasis
• Screen for hepatitis C on entry to care
  • At-risk seronegative individuals should be screened at least annually
• Consider type specific HSV serologic testing for those presenting for an STD evaluation
  • Approximately 70% of persons with HIV are HSV-2 seropositive | 95% are seropositive for either HSV-1 or HSV-2
  • HSV-2 infection increases the risk of HIV acquisition two- to three-fold and in coinfected patients
  • HSV-2 reactivation results in increases in HIV RNA levels in blood and genital secretions
• Screen on entry to care for hepatitis B with HBsAg, anti-HBc and/or anti-HBs
  • Offer vaccination to seronegative individuals with hepatitis B or combined hepatitis A and B vaccine
  • Recheck immunity after vaccination complete

SYNOPSIS:

While it is critical to remain vigilant with regard to STDs and pelvic infections, women with ulcerative conditions of the genitalia, including syphilis and herpes, are at increased risk of HIV acquisition and transmission to partners, lending an urgency to prompt treatment or suppression (see separate entry on ulcerative conditions).

KEY POINTS:

• Bacterial vaginosis is more prevalent/persistent in HIV-positive women
  • Diagnosis and treatment options are the same
• Vulvovaginal candidiasis is more common among HIV-positive women and associated with decreased CD4+ counts
  • Treatment is the same as for HIV-negative women
  • For azole-refractory Candida glabrata vaginitis
    • Boric acid 600 mg vaginal suppository once daily for 14 days
  • Note: Severe or recurrent vaginitis should be treated with oral fluconazole (100 to 200 mg) or topical antifungals for ≥7 days
• Treatment for gonorrhea/chlamydia is the same as for HIV-negative women
  • Retest 3 months after treatment as reinfection is common
• Pelvic inflammatory disease is treated with the same antimicrobials for the same duration as for HIV-negative
  • There is a greater incidence of tubo-ovarian abscess among HIV-positive, but overall response to therapy is the same as for HIV-negative
• Trichomoniasis is more prevalent among HIV-positive and should be treated with a one week course of metronidazole
• Parasitic conditions such as scabies or pediculosis pubis are treated the same regardless of HIV status

Learn More – Primary Sources:

ACOG Practice Bulletin 167: Gynecologic Care for Women and Adolescents with Human Immunodeficiency Virus

NIH Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

CDC: Sexually Transmitted Infections Treatment Guidelines 2021