What is the recommended treatment for oral candidiasis, including first‑line topical agents and indications for systemic therapy in patients who are pregnant, immunocompromised, diabetic, or using inhaled corticosteroids?

Treatment of Oral Thrush

For mild oral thrush, start with topical clotrimazole troches 10 mg five times daily or miconazole mucoadhesive buccal 50-mg tablet once daily for 7-14 days; for moderate to severe disease or in immunocompromised patients, use oral fluconazole 100-200 mg daily for 7-14 days. 1

First-Line Treatment Algorithm

Mild Disease (Immunocompetent Patients)

• Clotrimazole troches 10 mg five times daily for 7-14 days is the preferred topical agent 1
• Alternative: Miconazole mucoadhesive buccal 50-mg tablet applied once daily for 7-14 days 1
• Second-line topical options include 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
• Clinical response should be evident within 48-72 hours 1

Moderate to Severe Disease or Immunocompromised Patients

• Oral fluconazole 100-200 mg daily for 7-14 days is the treatment of choice 1
• Fluconazole achieves cure rates of 84-100% compared to nystatin's 32-51% in head-to-head trials 2
• In HIV-infected patients, symptomatic relapses occur sooner with topical therapy than with fluconazole, making systemic therapy preferred 3, 2
• Improvement typically occurs within 5-7 days 1

Special Populations

Pregnant Patients

• Topical agents (clotrimazole or nystatin) are preferred to avoid systemic azole exposure 1
• If systemic therapy is absolutely necessary, fluconazole should be used at the lowest effective dose for the shortest duration 1

Diabetic Patients

• Optimize glycemic control as a critical adjunct to antifungal therapy 1
• Fluconazole 100-200 mg daily for 7-14 days is recommended due to higher relapse rates with topical therapy in this population 1, 2

Patients Using Inhaled Corticosteroids

• Instruct patients to rinse mouth thoroughly after each inhaler use to prevent recurrence 1
• Either topical or systemic therapy is appropriate depending on severity 1
• Address the underlying cause by reviewing inhaler technique and reinforcing mouth-rinsing 1

Denture Wearers

• Disinfection of the denture is essential in addition to antifungal therapy—treatment will fail without this step 1
• Remove dentures at night and soak in chlorhexidine or dilute bleach solution 1
• Treat with topical or systemic antifungals as indicated by severity 1

Fluconazole-Refractory Disease

When oral thrush persists after 7-14 days of fluconazole therapy:

• Itraconazole solution 200 mg once daily for up to 28 days (64-80% response rate) 1, 2
• The solution formulation must be used—capsules have erratic absorption and are inferior 4
• Vigorously swish 10 mL in the mouth for several seconds before swallowing 4
• Take without food if possible for optimal absorption 4

Alternative options for refractory disease:

• Posaconazole suspension 400 mg twice daily for 3 days, then 400 mg daily for up to 28 days 1
• Voriconazole 200 mg twice daily 1
• Amphotericin B deoxycholate oral suspension 100 mg/mL four times daily 1

Esophageal Candidiasis

If the patient has dysphagia or odynophagia in addition to oral thrush, assume esophageal involvement and treat systemically—topical therapy is completely ineffective for esophageal disease. 3, 5, 2

• Fluconazole 200-400 mg (3-6 mg/kg) daily for 14-21 days is the standard treatment 3, 2
• For patients unable to swallow, use IV fluconazole 400 mg (6 mg/kg) daily 3, 5
• A diagnostic trial of fluconazole is appropriate before endoscopy; most patients with esophageal candidiasis will have symptom resolution within 7 days 3, 2
• Topical agents cannot reach therapeutic concentrations in the esophageal mucosa and will fail 5, 2

Recurrent Infections

HIV-Infected Patients

• Antiretroviral therapy is the most effective long-term strategy for reducing mucosal candidiasis 2
• For frequent recurrences, suppressive therapy with fluconazole 100 mg three times weekly may be necessary 3, 1
• Continuous suppressive therapy reduces relapse rates but increases risk of microbiological resistance 3

Other Immunocompromised Patients

• Suppressive therapy with fluconazole 100-200 mg three times weekly is recommended for recurrent infections 3
• Chronic suppressive therapy should be used judiciously to minimize resistance development 2

Critical Pitfalls to Avoid

• Do not use topical therapy for esophageal candidiasis—it will fail because topical agents cannot reach the esophageal mucosa 5, 2
• Do not use ketoconazole or itraconazole capsules as alternatives to fluconazole—they have variable absorption and are less effective 2, 4
• Do not overlook dentures in denture wearers—denture-related candidiasis requires disinfection of the prosthesis for definitive cure 1, 2
• Do not assume topicals are "safer" to avoid resistance—resistance develops with both topical and systemic therapy 2
• Do not continue topical nystatin in NPO patients—it is completely ineffective without swallowing 5
• For immunocompromised patients, favor fluconazole over topicals due to lower relapse rates 2

Drug Interactions and Monitoring

• Fluconazole inhibits CYP2C19 and reduces clopidogrel's antiplatelet effect—monitor closely in patients on antiplatelet therapy 5
• Check renal function and adjust fluconazole dosing accordingly, especially in critically ill patients 5
• For itraconazole, be aware of more erratic bioavailability and drug interactions compared to fluconazole 5