What is the treatment for fungal infections?

Treatment of Fungal Infections

The treatment of fungal infections requires specific antifungal agents tailored to the type of infection, with fluconazole being the first-line treatment for most Candida infections, voriconazole for invasive aspergillosis, and amphotericin B formulations for severe systemic fungal infections. 1

Treatment Based on Type of Fungal Infection

Candidiasis

Candidemia (Bloodstream Infection)

• For non-neutropenic patients: Start with fluconazole, an echinocandin (caspofungin), or amphotericin B deoxycholate (AmB-d) 1
• For critically ill patients or those with recent azole exposure: Favor an echinocandin 1
• For less critically ill patients with no history of azole exposure: Fluconazole is preferred 1
• Remove all intravascular catheters if possible to reduce mortality 1
• Treat for 14 days after the first negative blood culture and resolution of symptoms 1

Species-Specific Treatment

• C. albicans: Fluconazole (susceptible isolates) 1
• C. parapsilosis: Fluconazole, liposomal amphotericin B (L-AmB), or voriconazole 1
• C. glabrata: AmB-d 0.7-1.0 mg/kg/day; consider fluconazole only if susceptibility confirmed 1
• C. krusei: Echinocandin, L-AmB, or voriconazole (intrinsically resistant to fluconazole) 1

Neutropenic Patients with Candidemia

• Treatment options: AmB-d 0.7-1.0 mg/kg/day IV, echinocandin, or voriconazole 1
• Treat for 2 weeks after first negative blood culture, symptom resolution, and neutropenia resolution 1
• Intravenous catheter removal is advised but controversial 1

Mucocutaneous Candidiasis

Oropharyngeal Candidiasis:

• First-line: Nystatin suspension 200,000-400,000 U orally four times daily for 7-14 days 1
• Alternatives: Fluconazole 100-200 mg/day, itraconazole 200 mg/day 1
• For children: Treat for 1-7 days for uncomplicated disease 1

Esophageal Candidiasis:

• First-line: Fluconazole 200-400 mg/day for 14-21 days until clinical improvement 1
• Alternatives: Itraconazole 200 mg/day, echinocandin, or voriconazole 1
• For severe cases: AmB-d 0.3-0.7 mg/kg/day IV 1

Urinary Tract Candida Infections

• Asymptomatic candiduria: Generally no treatment needed except in high-risk patients 1
• Symptomatic cystitis: Fluconazole 200 mg daily for 14 days 1
• Pyelonephritis: Fluconazole 200-400 mg daily for 14 days 1
• For suspected disseminated candidiasis with pyelonephritis: Treat as candidemia 1

Invasive Aspergillosis

• First-line: Voriconazole (FDA-approved for invasive aspergillosis) 2
• Alternatives: Liposomal amphotericin B (L-AmB), echinocandin 1
• Treatment duration: Until resolution or stabilization of all clinical and radiographic manifestations 1
• Surgical intervention may be needed for certain pulmonary lesions near vital structures 1

Invasive Zygomycosis

• CNS infections: L-AmB with mandatory surgical resection of infected tissue 1
• Other sites: AmB-d or L-AmB with aggressive surgical debridement 1
• High-dose therapy may be considered when surgical intervention is not feasible 1

Special Considerations

Neonatal Candidiasis

• Treatment options: AmB-d 1.0 mg/kg/day, fluconazole 12 mg/kg/day, or echinocandin 1
• Diagnostic workup should include lumbar puncture, ophthalmoscopic examination, and imaging of genitourinary tract, liver, and spleen if blood cultures remain positive 1
• Treat for 3 weeks for candidemia without persistent fungemia or metastatic complications 1

CNS Fungal Infections

• For Candida: AmB-d with or without flucytosine; fluconazole 400-800 mg for patients unable to tolerate AmB-d 1
• For Aspergillosis: Voriconazole (crosses blood-brain barrier) 1
• Remove intraventricular devices if present 1
• Continue treatment until resolution of all signs, symptoms, CSF abnormalities, and radiologic abnormalities 1

Chronic Disseminated Candidiasis

• Treatment options: Fluconazole, L-AmB, AmB-d, echinocandin, or voriconazole in selected situations 1
• Continue treatment until lesions have resolved (typically 3-6 months) 1
• Consider step-down therapy with fluconazole or voriconazole in stable patients 1

Common Pitfalls and Caveats

• Drug interactions: Azole antifungals have significant drug interactions, particularly with immunosuppressants, anticonvulsants, and other medications 3
• Toxicity concerns: Long-term azole use can cause hepatotoxicity and hormone-related effects 3
• Resistance development: Increasing fungal resistance necessitates appropriate drug selection based on susceptibility when available 4
• Misdiagnosis: Candida isolated from respiratory tract rarely indicates infection and typically doesn't require treatment 1
• Inadequate duration: Premature discontinuation of therapy can lead to relapse; follow recommended duration based on infection site 1
• Pregnancy considerations: AmB-d is the treatment of choice for systemic fungal infections in pregnant women 5

Emerging Treatments

• Newer echinocandins and second-generation triazoles have expanded treatment options for resistant infections 6
• Posaconazole is the only azole with activity against zygomycete fungi 6
• Combination antifungal therapy may be appropriate in selected patients with invasive fungal infections, but remains empiric 6