Treatment of Systemic Fungal Infections
For systemic fungal infections, liposomal amphotericin B at 3-5 mg/kg intravenously daily, with or without oral flucytosine (25 mg/kg four times daily), is the recommended first-line treatment, followed by step-down therapy with fluconazole 400-800 mg daily once the patient has stabilized. 1
Treatment Selection Based on Fungal Type
Candidiasis (Systemic/Invasive)
Initial Treatment
Nonneutropenic patients:
- Fluconazole 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily
- Liposomal amphotericin B (L-AmB) 3-5 mg/kg daily
- Echinocandin (caspofungin 70 mg loading dose, then 50 mg daily) 1
Neutropenic patients:
- Echinocandin preferred (caspofungin 70 mg loading dose, then 50 mg daily)
- L-AmB 3-5 mg/kg daily 1
CNS Candidiasis:
- L-AmB 5 mg/kg daily, with or without flucytosine 25 mg/kg four times daily
- Step-down to fluconazole 400-800 mg daily after clinical improvement 1
Species-Specific Considerations
- C. glabrata: Echinocandin or L-AmB initially; fluconazole only if susceptibility confirmed
- C. krusei: Echinocandin, L-AmB, or voriconazole (fluconazole-resistant) 1
- C. parapsilosis: Fluconazole preferred over echinocandins 1
Histoplasmosis (Systemic)
- Initial treatment: Amphotericin B formulation until clinical improvement
- Step-down therapy: Itraconazole 200 mg twice daily (solution preferred for better absorption)
- Duration: At least 12 weeks; longer for immunocompromised patients 1
- Therapeutic drug monitoring: Recommended for itraconazole; target serum concentration ≥1.0 μg/mL 1
Treatment Duration and Monitoring
Duration
- Candidemia without complications: 14 days after first negative blood culture and resolution of symptoms 1
- CNS infections: Continue until all signs, symptoms, CSF abnormalities, and radiological abnormalities have resolved 1
- Chronic disseminated candidiasis: Until lesions have resolved (usually months) 1
Monitoring
- Renal function: Frequent monitoring, especially with amphotericin B formulations 2
- Liver function: Monitor hepatic enzymes before therapy and at 1,2, and 4 weeks, then every 3 months during azole therapy 1
- Serum electrolytes: Regular monitoring of potassium and magnesium levels 2
- Blood cultures: Daily or every other day until negative 1
- Ophthalmologic examination: Recommended for all patients with candidemia 1
Special Considerations
Device-Related Infections
- Infected CNS devices (shunts, drains): Remove if possible
- If device cannot be removed: Consider intrathecal amphotericin B deoxycholate (0.01-0.5 mg in 2 mL 5% dextrose) 1
- Infected vascular catheters: Remove when possible 1
Drug Interactions and Toxicity Management
- Nephrotoxic medications: Use with caution when combined with amphotericin B
- Corticosteroids: May potentiate amphotericin B-induced hypokalemia
- Digitalis glycosides: Monitor for toxicity due to amphotericin B-induced hypokalemia
- Imidazoles: May induce fungal resistance to amphotericin B 2
Common Pitfalls to Avoid
Delayed initiation of therapy: Start antifungal therapy within 24 hours of positive blood culture for candidemia 1
Inadequate source control: Failure to remove infected devices when possible
Insufficient duration of therapy: Treat until complete resolution of infection, not just symptom improvement
Inappropriate drug selection: Consider local resistance patterns and patient-specific factors (renal function, drug interactions)
Inadequate monitoring: Regular assessment of therapeutic response and drug toxicity is essential
Failure to transition to oral therapy: Step-down to oral therapy (usually fluconazole) when appropriate to reduce toxicity and cost
Missing occult sites of infection: Perform thorough evaluation for metastatic foci, especially in persistent candidemia
By following these evidence-based recommendations and avoiding common pitfalls, clinicians can optimize outcomes for patients with systemic fungal infections, reducing morbidity and mortality associated with these challenging infections.