What is the recommended treatment for esophageal candidiasis?

Treatment of Esophageal Candidiasis

For esophageal candidiasis, oral fluconazole 200-400 mg on day 1, followed by 200 mg daily for 14-21 days is the treatment of choice, with treatment continuing for at least 14 days and for at least 2 weeks following resolution of symptoms. 1, 2, 3

First-Line Systemic Therapy

Systemic antifungal therapy is required for effective treatment of esophageal candidiasis—topical therapy is inadequate. 1

Preferred regimen:

• Fluconazole 200-400 mg orally on day 1, then 200 mg daily for 14-21 days 1, 2, 3
• The FDA-approved dosing is 200 mg on day 1, followed by 100 mg daily, with doses up to 400 mg/day based on clinical response 3
• Most patients show clinical improvement within 48-72 hours of starting therapy 1, 2

For patients unable to tolerate oral therapy:

• Intravenous fluconazole at the same dosage (200-400 mg daily) 1, 2, 4

Empiric Treatment Without Endoscopy

A diagnostic trial of antifungal therapy is often appropriate before endoscopy, particularly when typical symptoms are present with concurrent oropharyngeal candidiasis. 1, 4 This approach is cost-effective given the high prevalence of Candida esophagitis in immunocompromised patients and the predictable response to fluconazole. 5, 6

Alternative First-Line Options

Itraconazole solution:

• 200 mg daily for 14-21 days is effective but less well-tolerated than fluconazole 1, 2
• Important caveat: Itraconazole capsules and ketoconazole are significantly less effective than fluconazole due to variable absorption and should be avoided 1, 2

Voriconazole:

• 200 mg twice daily for 14-21 days is equally efficacious but has more adverse effects and drug interactions 2

Echinocandins (for patients intolerant to azoles):

• Micafungin 150 mg IV daily 1, 2, 4
• Caspofungin 70 mg IV loading dose, then 50 mg daily 1, 2, 4
• Anidulafungin 200 mg IV loading dose, then 100 mg daily 1, 2, 4
• Important limitation: Echinocandins are associated with higher relapse rates (28% vs 17% with fluconazole at 4 weeks) compared to fluconazole, though they are well-tolerated 2, 7

Management of Fluconazole-Refractory Disease

Treatment failure is defined as persistence of symptoms after 7-14 days of appropriate therapy. 1, 2

Second-line options for refractory disease:

• Itraconazole solution >200 mg daily (effective in approximately two-thirds of fluconazole-refractory cases) 1, 4
• Posaconazole oral suspension 400 mg twice daily for 3 days, then 400 mg daily (effective in 75% of azole-refractory cases) 1
• Voriconazole 200 mg twice daily 1, 4

For azole-resistant disease:

• Echinocandins for 14-21 days (micafungin 150 mg daily, caspofungin 70 mg loading then 50 mg daily, or anidulafungin 200 mg daily) 1, 2, 4
• Amphotericin B deoxycholate 0.3-0.7 mg/kg IV daily as a last resort 1, 2

Prevention of Recurrence

Chronic suppressive therapy is not routinely recommended for most patients due to concerns about resistance, drug interactions, and cost. 1 However, specific situations warrant secondary prophylaxis:

Indications for suppressive therapy:

• Patients with disabling recurrent infections 1
• Patients with history of documented esophageal candidiasis and CD4 counts <200 cells/μL 1
• Patients with fluconazole-refractory disease who responded to echinocandins or other agents (high relapse rate until immune reconstitution) 1

Suppressive regimen:

• Fluconazole 100-200 mg three times weekly 1, 2, 4

For HIV-infected patients:

• Antiretroviral therapy is strongly recommended to reduce the incidence of recurrent infections and is the most important intervention for preventing relapse 1, 2, 4

Monitoring and Safety

Clinical monitoring:

• Expect symptom improvement within 48-72 hours in most patients 1, 2
• If prolonged azole therapy (>21 days) is anticipated, periodic monitoring of liver function tests should be considered 1, 2

Common adverse effects:

• Azoles: gastrointestinal upset, hepatotoxicity with prolonged use 1
• Echinocandins: generally safe with minimal side effects; histamine-related infusion reactions, transaminase elevation, and rash may occur 1

Critical Pitfalls to Avoid

Avoid itraconazole capsules and ketoconazole as they have variable absorption and are significantly less effective than fluconazole or itraconazole solution. 1, 2

Do not use topical therapy alone for esophageal candidiasis—systemic therapy is required for effective treatment. 1

Consider azole resistance in patients with advanced immunosuppression (CD4 <50 cells/μL) who have received multiple courses of azole antifungals—these patients may require echinocandins as initial therapy. 1, 2

Recognize that asymptomatic esophageal candidiasis is common in HIV-infected patients with oropharyngeal candidiasis, occurring in up to 43% of cases. 8