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

Note: Diagnosis based on history and physical alone are unreliable |  If pH paper, KOH, and microscopy are not available, FDA approved commercial tests are available

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)
  • Note: Boric acid should not be used during pregnancy or lactation
• If unresponsive patient, should be referred to a subspecialist

Pregnancy

• Topical imidazole therapy for “probably” 7 days (CDC)

Note: Oral fluconazole used at high doses for extended periods of time may be associated with a small increase in birth defects | There have been conflicting studies regarding miscarriage and stillbirth | The FDA did not find conclusive evidence for risk of stillbirth or miscarriage with single 150 mg dose (see ‘Related ObG Topics’ below) | The FDA does “advise cautious prescribing of oral fluconazole in pregnancy”

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

Is Oral Fluconazole Use in Pregnancy Linked to Stillbirths?

BACKGROUND AND PURPOSE:

• Despite recommendations against oral fluconazole during pregnancy, 4% of pregnant women in the US are still using this medication
• There have been studies associating stillbirth risk with higher doses (>300 mg) but not lower doses (see ‘Related ObG Entries’ below)
• Pasternak et al. (JAMA, 2018) evaluated the association between oral fluconazole use and stillbirth

METHODS:

• Nationwide Retrospective Cohort study
  • Women with singleton pregnancies and stillbirths in Sweden (2006-2104)
• Exclusions included pregnancies missing the following information
  • ID | GA | Nonresidence | Fluconazole or any nonfluconazole oral azole antifungal within 28 days of conception
• Primary outcome: Any fluconazole exposure during pregnancy
  • Stillbirth
  • Neonatal death (0-27 days after live birth)
• Secondary analyses based on dose

RESULTS:

• 1,485,316 pregnancies were included
  • Stillbirth analysis included 10,669 exposed and 106,690 unexposed pregnancies
  • Neonatal outcome analysis included 10,640 exposed and 106,387 unexposed pregnancies
• There were no significant differences when comparing exposed to unexposed
  • Stillbirth: 7 vs 3.6 (per 1000); Hazard ratio [HR] 0.76; 95% CI, 0.52-1.10
  • Neonatal death: 2 vs 1.7 (per 1000); Risk ratio [RR] 0.73; 95% CI, 0.42-1.29
• Dose did not alter lack of association

CONCLUSION:

• There was no association between fluconazole use in pregnancy and increased risk of still birth or neonatal death
• The authors do recommend additional studies and data review prior to changing recommendations

Learn More – Primary Sources:

Oral Fluconazole in Pregnancy and Risk of Stillbirth and Neonatal Death