Treatment Options for Fungal Infections
The choice of antifungal therapy depends critically on the specific type of fungal infection, infection site, patient immune status, and severity of illness, with treatment ranging from topical agents for superficial infections to systemic therapy for invasive disease.
Invasive Candidiasis
Candidemia in Non-Neutropenic Patients
- Remove all intravascular catheters if possible and initiate empirical therapy for critically ill patients with multiple risk factors 1
- First-line options include echinocandins (caspofungin 70 mg loading, then 50 mg daily; micafungin 100 mg daily; anidulafungin 200 mg loading, then 100 mg daily), amphotericin B deoxycholate (AmB-d) 0.5-1.0 mg/kg/d, liposomal amphotericin B (L-AmB) 3-5 mg/kg daily, fluconazole (800 mg loading, then 400 mg daily), or voriconazole 1
- Favor echinocandins for moderately to severely ill patients, those with recent azole exposure, or those at high risk for C. glabrata or C. krusei infection 1
- Favor fluconazole for less critically ill patients without recent azole exposure 1
- Transfer stable patients with fluconazole-susceptible isolates (e.g., C. albicans) from echinocandin to fluconazole for step-down therapy 1
- Treat for at least 14 days following resolution of symptoms or last positive culture, whichever is longer 1
Candidemia in Neutropenic Patients
- Intravenous catheter removal is advised but controversial 1
- AmB-d 0.7-1.0 mg/kg/d IV, echinocandins, or voriconazole (if additional mold coverage desired) are recommended 1
- Treat for 2 weeks after first negative blood culture, resolution of symptoms, and resolution of neutropenia 1
Site-Specific Candida Infections
CNS Candidiasis:
- AmB-d with or without flucytosine (5-FC) 25 mg/kg four times daily is the treatment of choice 1
- Fluconazole 400-800 mg daily for patients unable to tolerate AmB-d 1
- Remove intraventricular devices and treat until all signs, symptoms, CSF abnormalities, and radiologic abnormalities resolve 1
Candida Endophthalmitis:
- AmB-d 0.7-1 mg/kg with 5-FC, fluconazole, L-AmB, voriconazole, or echinocandin 1
- Perform diagnostic vitreal aspiration if etiology unknown 1
- Surgical intervention for severe endophthalmitis or vitreitis 1
- Treat for at least 4-6 weeks with repeated examinations to verify resolution 1
Urinary Tract Infections:
- Asymptomatic cystitis: therapy not usually needed except in high-risk surgical patients, neonates, or neutropenic patients 1
- Symptomatic cystitis: fluconazole 200 mg daily for 14 days or AmB-d 0.3-0.6 mg/kg/d 1
- Pyelonephritis: fluconazole 200-400 mg daily for 14 days or AmB-d with or without 5-FC for 7-14 days 1
Mucocutaneous Candidiasis
Oropharyngeal Candidiasis:
- Nystatin suspension 200,000-400,000 U po qid, fluconazole 100-200 mg/d po, or itraconazole 200 mg/d 1
- Treat for 7-14 days (1-7 days in children) for uncomplicated disease 1
Esophageal Candidiasis:
- Fluconazole 200-400 mg/d or itraconazole 200 mg/d po are first-line 1, 2
- Alternatives include echinocandins, voriconazole, or AmB-d 0.3-0.7 mg/kg/d IV 1
- Treat for 14-21 days until clinical improvement 1
Invasive Aspergillosis
Primary Therapy:
- Voriconazole is the treatment of choice with loading dose 400 mg (6 mg/kg) every 12 hours for two doses on Day 1, then maintenance 200 mg (3-4 mg/kg) bid 1, 2, 3
- Alternatives include L-AmB 3-5 mg/kg daily, echinocandins, or itraconazole 1
- AmB-d 1.0-1.5 mg/kg/d is also effective 1
- Treat until resolution or stabilization of all clinical and radiographic manifestations 1
Site-Specific Aspergillosis:
- CNS aspergillosis: voriconazole, AmB-d, echinocandin, L-AmB, or itraconazole with surgical resection if possible 1
- Sinus/endocarditis: voriconazole or L-AmB with surgical intervention if possible 1
- Chronic cavitary pulmonary aspergillosis: itraconazole or voriconazole as oral therapy 1
- Aspergilloma: surgical resection under some circumstances 1
Invasive Cryptococcosis
CNS or Disseminated Disease:
- AmB-d 0.7-1.0 mg/kg/d plus flucytosine 25 mg/kg four times daily for 2 weeks (induction), followed by fluconazole consolidation 1
- Alternative: L-AmB 4-6 mg/kg/d for 6-10 weeks 1
- Management of elevated intracranial pressure is critical: keep initial CSF opening pressure <200 mmH₂O with serial lumbar drainage if pressure ≥250 mmH₂O 1
- Treat for 6-18 months total 1
- For AIDS patients, start HAART therapy 4-6 weeks after starting antifungal therapy 1
- Maintenance therapy with fluconazole 200 mg/d until CD4 >100/μL and undetectable HIV RNA for 3 months 1
Cryptococcal Pneumonia:
- AmB-d, itraconazole, fluconazole, or voriconazole 1
- Treat for 6-12 months in immunocompetent patients 1
- Treat immunocompromised patients as disseminated infection 1
Invasive Zygomycosis (Mucormycosis)
- L-AmB is the treatment of choice with high doses (up to 10 mg/kg/d for CNS disease) 1
- AmB-d 3-10 mg/kg/d is an alternative 1
- Aggressive surgical debridement of infected tissue is mandatory 1
- High-dose therapy can be considered when surgical intervention is not feasible 1
Scedosporiosis and Fusariosis
- Voriconazole is indicated for serious infections caused by Scedosporium apiospermum and Fusarium species in patients intolerant of or refractory to other therapy 2
- Therapy must be initiated with IV voriconazole loading dose followed by maintenance dosing 2
Important Clinical Considerations
Common Pitfalls:
- Fluconazole has no activity against molds (Aspergillus, Fusarium, Scedosporium) and should not be used for these infections 3
- Echinocandins have limited CNS penetration and are not first-line for CNS infections 3
- Voriconazole causes visual disturbances, photosensitivity, and has significant drug interactions with anticonvulsants 1, 4, 5
- Monitor liver function with all azoles as hepatotoxicity occurs in 1-13% of patients 4, 5
- Amphotericin B requires close monitoring of renal function, electrolytes (especially potassium and magnesium), and blood counts 6
Drug Selection Strategy: