What is the first‑line therapy for oral candidiasis in a healthy adult, and how should treatment be adjusted for infants, HIV‑positive or immunosuppressed patients, and refractory cases?

Treatment of Oral Candidiasis (Thrush)

For healthy adults with moderate to severe oral thrush, oral fluconazole 100–200 mg once daily for 7–14 days is the first-line therapy, offering superior efficacy and convenience compared to topical agents. 1

First-Line Treatment by Disease Severity

Mild Disease in Healthy Adults

• Topical therapy is preferred: Clotrimazole troches 10 mg five times daily or miconazole mucoadhesive buccal tablets 50 mg once daily for 7–14 days 1, 2
• Alternative topical option: Nystatin suspension (100,000 U/mL) 4–6 mL four times daily or nystatin pastilles (200,000 U each) 1–2 pastilles four times daily for 7–14 days 1
• Topical agents achieve clinical cure but patients relapse more quickly than with systemic therapy 3

Moderate to Severe Disease in Healthy Adults

• Oral fluconazole 100–200 mg once daily for 7–14 days is the treatment of choice 1, 2
• Fluconazole achieves 84–90% clinical cure rates, significantly superior to nystatin (32–54%) 2, 4
• Clinical improvement typically occurs within 48–72 hours, but completing the full 7–14 day course is essential to prevent relapse 1, 2

Treatment Adjustments for Special Populations

Infants (>3 Months Old)

• Weight-based dosing: Fluconazole 3–6 mg/kg daily for 7–14 days 2
• For mild disease, miconazole gel 25 mg four times daily is significantly superior to nystatin suspension, achieving 84.7% cure by day 5 versus 21.2% with nystatin 5
• Maximum single dose should not exceed 100 mg 6

HIV-Positive and Immunosuppressed Patients

• Use the same fluconazole dosing as healthy adults: 100–200 mg daily for 7–14 days 1, 2
• Optimizing antiretroviral therapy is the most critical intervention to reduce recurrence rates, more effective than antifungal choice alone 2, 7
• Relapse occurs in approximately 40% of immunocompromised individuals despite adequate antifungal treatment 2
• For patients with CD4+ counts <150 cells/µL and frequent recurrences, consider chronic suppressive therapy with fluconazole 100 mg three times weekly 6

Pregnant Patients

• Fluconazole is contraindicated for chronic or prolonged use (>150 mg or >7 days) due to teratogenic risk 1, 6
• Topical azoles are the preferred alternative: Clotrimazole or miconazole applied topically for 7–14 days 6
• If systemic therapy is unavoidable, limit to ≤7 days of fluconazole 100 mg daily after careful risk-benefit discussion 6

Management of Refractory Cases

First-Line Alternative for Fluconazole-Refractory Disease

• Itraconazole oral solution 200 mg once daily for up to 28 days responds in approximately two-thirds of fluconazole-refractory cases 1, 2
• Itraconazole solution is better absorbed than capsules and comparable in efficacy to fluconazole for initial treatment 1

Second-Line Alternatives

• Posaconazole suspension: 400 mg twice daily for 3 days, then 400 mg once daily for up to 28 days, achieving approximately 75% efficacy in refractory infections 1, 2
• Voriconazole: 200 mg orally twice daily 1, 2

Third-Line Options for Severe Refractory Disease

• Intravenous echinocandins:
  • Caspofungin: 70 mg loading dose, then 50 mg daily 1, 7
  • Micafungin: 100 mg daily 1, 7
  • Anidulafungin: 200 mg loading dose, then 100 mg daily 1, 7
• Amphotericin B deoxycholate oral suspension: 100 mg/mL four times daily (not available in the United States) 1
• Intravenous amphotericin B: 0.3–0.6 mg/kg daily for severe refractory cases 1

Chronic Suppressive Therapy for Recurrent Thrush

Indications

• Reserve for patients with ≥4 episodes per year that markedly impair quality of life 2, 7
• Routine chronic suppression is generally discouraged due to cost, drug interactions, and resistance risk 1

Recommended Regimen

• After treating the acute episode with fluconazole 100–200 mg daily for 7–14 days, initiate maintenance therapy:
  • Fluconazole 100 mg three times weekly (e.g., Monday-Wednesday-Friday) for at least 3–6 months 2, 6, 7
  • Alternative: Fluconazole 150 mg once weekly 2
• This regimen is supported by strong recommendations with high-quality evidence 2, 6

Resistance Considerations

• The incidence of fluconazole resistance is comparable between continuous daily therapy and intermittent pulse therapy (approximately 46–56%), but clinical response generally remains satisfactory 6
• HIV-infected patients on chronic fluconazole have higher risk of developing azole-resistant Candida (particularly C. glabrata) 6

Critical Clinical Pitfalls and How to Avoid Them

Denture-Related Candidiasis

• Antifungal therapy alone will fail without simultaneous denture disinfection 2, 7
• Prescribe fluconazole as above and provide explicit denture-cleaning instructions 2

Premature Treatment Discontinuation

• Stopping therapy when symptoms resolve after 3–5 days markedly increases relapse risk 2, 7
• Always complete the full 7–14 day course even if asymptomatic by day 3 2

Suspected Esophageal Involvement

• When dysphagia or odynophagia suggests esophageal candidiasis, initiate a therapeutic trial of fluconazole 200–400 mg daily for 14–21 days before endoscopy 2
• This approach is more cost-effective than immediate endoscopic evaluation 2

Monitoring for Hepatotoxicity

• Azole therapy extending beyond 7–10 days can cause hepatotoxicity 1, 6
• If treatment is expected to exceed 21 days, obtain baseline and periodic liver function tests 1, 6

Resistance Testing

• In refractory cases, obtain antifungal susceptibility testing to guide therapy, as it is predictive of clinical response to fluconazole and itraconazole 7
• Non-albicans Candida species (especially C. glabrata and C. krusei) are more likely to be fluconazole-resistant 2