What is the recommended treatment for vulvovaginal candidiasis in a woman, including first‑line therapy, alternatives if fluconazole is contraindicated, and management of recurrent infection or pregnancy?

Treatment of Vulvovaginal Candidiasis

First-Line Therapy for Uncomplicated Disease

For uncomplicated vulvovaginal candidiasis, prescribe a single oral dose of fluconazole 150 mg, which achieves >90% clinical response rates and is equivalent in efficacy to multi-day topical azole therapy. 1, 2

• Uncomplicated disease is defined by mild-to-moderate symptoms (pruritus, discharge), sporadic episodes (not recurrent), likely Candida albicans etiology, and immunocompetent host status. 2
• Alternative first-line options include short-course topical azoles: clotrimazole 500 mg vaginal tablet (single application), miconazole 200 mg suppository once daily for 3 days, or terconazole 0.8% cream 5 g intravaginally for 3 days—all achieving comparable 80-90% clinical cure rates. 2
• Topical agents may cause local burning or irritation in some patients, whereas oral fluconazole avoids this local effect but carries systemic drug interaction risks. 3

Alternatives When Fluconazole is Contraindicated

If fluconazole cannot be used, prescribe topical azole therapy for 7 days as the primary alternative. 4, 1

• Specific topical regimens include clotrimazole, miconazole, or terconazole preparations applied intravaginally for 7 consecutive days. 4
• Itraconazole 200 mg daily for 3 days is another oral alternative if azole class drugs are acceptable but fluconazole specifically is contraindicated. 3
• Critical drug interactions with fluconazole include: warfarin (elevated INR and bleeding risk), oral hypoglycemics (hypoglycemia), phenytoin (toxicity), calcium-channel blockers, protease inhibitors, and calcineurin inhibitors (tacrolimus/cyclosporine). 2

Management of Severe Vulvovaginal Candidiasis

For severe disease—defined by extensive vulvar erythema, edema, excoriation, and fissure formation—prescribe fluconazole 150 mg every 72 hours for 3 doses (total 450 mg over 6 days) or topical azole therapy for 7-14 days. 4, 1, 2

• Severe vulvovaginitis has lower clinical response rates with short-course therapy, necessitating extended treatment duration. 4
• Women with underlying debilitating conditions (uncontrolled diabetes, corticosteroid treatment) require the same prolonged 7-14 day conventional antimycotic treatment with efforts to correct modifiable conditions. 4

Management of Recurrent Vulvovaginal Candidiasis

For recurrent disease (≥4 episodes per year), initiate induction therapy with fluconazole 150 mg every 72 hours for 3 doses or topical azole for 10-14 days, followed by maintenance therapy with fluconazole 150 mg weekly for 6 months. 1, 2

• Maintenance therapy reduces recurrence rates significantly: 90.8% of women remain disease-free at 6 months with weekly fluconazole versus 35.9% with placebo, though 30-40% will experience recurrence after discontinuation. 4, 5
• An individualized degressive regimen (200 mg weekly for 2 months, then biweekly for 4 months, then monthly for 6 months) achieved 90% disease-free status at 6 months and 77% at 1 year in research settings. 6
• Women with poor response to maintenance therapy typically have longer disease duration and harbor more non-albicans Candida species. 6
• Ketoconazole maintenance (100 mg daily) is an alternative but requires monitoring for hepatotoxicity (1 in 10,000-15,000 risk). 4

Management of Non-Albicans Species

For non-albicans vulvovaginal candidiasis (particularly C. glabrata), prescribe longer duration therapy (7-14 days) with a non-fluconazole azole as first-line, or boric acid 600 mg vaginal capsule once daily for 14 days if recurrence occurs. 4, 1, 2

• Non-albicans species are found in 10-20% of recurrent vulvovaginal candidiasis cases and respond less well to conventional azole therapies. 4
• Boric acid achieves approximately 70% clinical and mycologic eradication rates. 4
• Additional options include nystatin 100,000 units vaginal suppositories daily or topical 4% flucytosine (specialist referral advised). 4, 1

Management During Pregnancy

In pregnant women, prescribe only topical azole therapy applied for 7 days; oral fluconazole is contraindicated due to association with spontaneous abortion. 4, 1

• Vulvovaginal candidiasis occurs frequently during pregnancy and requires extended topical treatment duration compared to non-pregnant women. 4
• No oral azole agents should be used during pregnancy. 1

Diagnostic Confirmation to Avoid Misdiagnosis

Before prescribing treatment, confirm diagnosis with wet-mount microscopy using 10% potassium hydroxide to visualize yeast or pseudohyphae, and measure vaginal pH (should be ≤4.5 for candidiasis). 1, 2

• Symptoms of pruritus, discharge, dysuria, and dyspareunia are nonspecific and can result from bacterial vaginosis, trichomoniasis, or non-infectious causes. 1, 2
• If wet mount is negative but symptoms persist, obtain vaginal culture to guide therapy and identify non-albicans species. 1, 2
• Vaginal pH >4.5 suggests bacterial vaginosis or trichomoniasis rather than candidiasis. 1, 2
• Do not treat asymptomatic colonization: 10-20% of women harbor Candida species without symptoms, and treatment is not indicated. 2

Management of Treatment Failure

If symptoms persist beyond 5-7 days or recur within 2 months, re-evaluate with repeat cultures to identify non-albicans species or azole resistance. 1, 2

• Treatment failure should prompt consideration of C. glabrata or C. krusei, which may require boric acid or nystatin suppositories. 1, 2
• Although C. albicans azole resistance is rare in vaginal isolates, surveillance of recurrent isolates for resistance development is prudent. 4

Special Populations: HIV-Infected Women

Treatment for vulvovaginal candidiasis in HIV-infected women should not differ from seronegative women, with identical response rates expected. 4, 1

• Symptomatic vulvovaginal candidiasis is more frequent in HIV-positive women and correlates with severity of immunodeficiency. 4
• Long-term prophylactic fluconazole 200 mg weekly is effective in reducing colonization and symptomatic disease but is not recommended for routine primary prophylaxis in the absence of recurrent disease. 4
• Recurrent vulvovaginal candidiasis should not be considered a sentinel sign to justify HIV testing, as it occurs frequently in immunocompetent populations. 4

Critical Pitfalls to Avoid

• Inadequate treatment duration: Complicated vulvovaginal candidiasis requires 7-14 days of therapy, not the single-dose regimen used for uncomplicated disease. 1
• Misattribution of symptoms: Vaginal irritation is commonly part of the underlying candidiasis itself, not necessarily a fluconazole adverse effect; confirm diagnosis before attributing symptoms to medication. 3
• Ignoring recurrence patterns: Women with history of recurrent vaginitis have significantly lower clinical and mycologic response rates (33/84 vs 177/266, p<0.001) and require maintenance therapy rather than episodic treatment. 7
• Using alternative/complementary therapies: Honey-based ointments, essential oils, and ginger-clotrimazole combinations show equal or inferior results to FDA-approved medications and lack regulation. 1