Recommended Antifungal Agents for Different Fungal Infections
The selection of antifungal agents should be based on the specific type of fungal infection, with fluconazole recommended for most Candida infections, voriconazole for invasive aspergillosis, and amphotericin B formulations for broad-spectrum coverage of invasive fungal infections. 1, 2
Major Classes of Antifungal Agents
The four main classes of antifungal drugs available for clinical use include:
- Polyenes (amphotericin B formulations)
- Azoles (fluconazole, itraconazole, voriconazole, posaconazole)
- Echinocandins (caspofungin, micafungin, anidulafungin)
- Pyrimidine analogues (flucytosine/5-FC) 3
Treatment Recommendations by Infection Type
Candida Infections
Candidemia/Invasive Candidiasis
- First-line: Fluconazole 400 mg (6 mg/kg) daily after 800 mg (12 mg/kg) loading dose
- Alternative options:
- Echinocandins: Caspofungin (70 mg loading, then 50 mg daily), Micafungin (100 mg daily), or Anidulafungin (200 mg loading, then 100 mg daily)
- Amphotericin B deoxycholate (AmB-d) 0.5-1.0 mg/kg/d
- Liposomal AmB (L-AmB) 3-5 mg/kg daily 1
- Duration: Treat for 3 weeks after last positive blood culture and resolution of symptoms 1
Chronic Disseminated Candidiasis
- First-line: Fluconazole
- Alternatives: L-AmB, AmB-d, echinocandins
- Duration: Continue until lesions resolve (typically 3-6 months) 1
CNS Candidiasis
- First-line: AmB-d with or without 5-FC
- Alternative: Fluconazole 400-800 mg (6-12 mg/kg) daily for patients unable to tolerate AmB-d
- Important: Remove intraventricular devices if present 1
Candida Endophthalmitis
- First-line: AmB-d 0.7-1 mg/kg with 5-FC
- Alternatives: Fluconazole, L-AmB, voriconazole, echinocandins
- Duration: At least 4-6 weeks 1
Urinary Tract Candida Infections
- Asymptomatic cystitis: Usually no therapy needed
- Symptomatic cystitis: Fluconazole 200 mg (3 mg/kg) daily for 14 days
- Pyelonephritis: Fluconazole 200-400 mg (3-6 mg/kg) daily for 14 days 1
Mucocutaneous Candidiasis
Oropharyngeal:
Esophageal:
- Fluconazole 200-400 mg/d
- Itraconazole 200 mg/d po
- Alternatives: Echinocandins, voriconazole
- Duration: 14-21 days until clinical improvement 1
Skin infections:
- Topical azoles (clotrimazole 1%, miconazole 2%, ketoconazole 2%) applied 2-3 times daily for 14 days
- For extensive infections: Add oral fluconazole 150 mg every 72 hours for 2-3 doses 2
Aspergillus Infections
Invasive Aspergillosis
- First-line: Voriconazole 6 mg/kg IV every 12 hours for first 24 hours, then 4 mg/kg IV every 12 hours or 200 mg oral every 12 hours 1, 4
- Alternatives:
- L-AmB 3-5 mg/kg daily
- Echinocandins (limited data for anidulafungin)
- Itraconazole 1
- Duration: Until resolution or stabilization of clinical and radiographic manifestations 1
CNS Aspergillosis
- First-line: Voriconazole
- Alternatives: AmB-d, echinocandins, L-AmB, itraconazole
- Important: Surgical resection of infected tissue if possible 1
Chronic Cavitary Pulmonary Aspergillosis
- First-line: Itraconazole or voriconazole (oral therapy) 1
Cryptococcal Infections
CNS or Disseminated Cryptococcosis
- First-line: AmB-d plus 5-FC for 2 weeks, followed by fluconazole
- Alternative: L-AmB for 6-10 weeks
- Important: Management of elevated intracranial pressure is critical 1
Cryptococcal Pneumonia
- First-line: AmB-d or fluconazole with or without 5-FC
- Alternatives: Itraconazole, voriconazole
- Duration: 6-12 months for immunocompetent patients 1
Zygomycosis (Mucormycosis)
Invasive Zygomycosis
- First-line: L-AmB (CNS involvement) or AmB-d (other sites)
- Dosage: High-dose L-AmB 4-6 mg/kg/d
- Important: Surgical resection of infected tissue is mandatory 1
Specific Dosing Information
Adults
Amphotericin B deoxycholate:
- Invasive candidiasis: 0.5-1.0 mg/kg/d
- Cryptococcosis: 0.7-1.0 mg/kg/d
- Invasive aspergillosis: 1.0-1.5 mg/kg/d
- Invasive zygomycosis: 3-10 mg/kg/d 1
Fluconazole:
- Loading: 800 mg (12 mg/kg) on Day 1
- Maintenance: 400 mg (6 mg/kg) daily for invasive candidiasis 1
Voriconazole:
- Loading: 6 mg/kg IV every 12 hours for first 24 hours
- Maintenance: 4 mg/kg IV every 12 hours or 200 mg oral every 12 hours
- For patients <40 kg: oral maintenance 100 or 150 mg every 12 hours 4
Echinocandins:
Pediatric Patients
Voriconazole (2 to <12 years and 12-14 years <50 kg):
- Loading: 9 mg/kg IV every 12 hours for first 24 hours
- Maintenance: 8 mg/kg IV every 12 hours or 9 mg/kg oral every 12 hours (max 350 mg every 12 hours) 4
Micafungin (4 months and older):
- ≤30 kg: 2 mg/kg/day for candidemia (max 100 mg daily)
30 kg: Same as adult dosing 5
Important Considerations
Dose Adjustments
Hepatic impairment:
- Voriconazole: Use half the maintenance dose in mild to moderate hepatic impairment 4
Renal impairment:
Drug Interactions and Adverse Effects
- Azoles: Be aware of drug-drug interactions and adverse effects, including visual disturbances (with voriconazole), elevated liver enzymes, and skin rashes 3
- Voriconazole: Beware of interaction between anticonvulsant therapy and voriconazole in CNS infections 1
Monitoring
- Evaluate response within 7 days of starting treatment
- Monitor liver function tests every 1-2 weeks during treatment
- Ophthalmological examination for all patients with candidemia 2
- For persistent or relapsing cryptococcal infections, check susceptibility of isolates 1
Prophylaxis Recommendations
- Candida: Fluconazole for high-risk patients (hematopoietic stem cell transplant recipients prior to engraftment, liver/pancreas/small bowel transplant recipients) 1
- Aspergillus: AmB-d, itraconazole for high-risk patients (allogeneic hematopoietic stem cell transplant recipients prior to engraftment, patients with GVHD) 1
- Immunocompromised patients: Consider posaconazole, voriconazole, or itraconazole 2
By following these evidence-based recommendations for antifungal therapy, clinicians can optimize treatment outcomes while minimizing adverse effects in patients with fungal infections.