What are the treatment options for fungal infections?

Treatment of Fungal Infections

The optimal treatment for fungal infections depends critically on the specific type of infection (superficial vs. invasive), the causative organism, and the patient's immune status, with azoles (fluconazole, voriconazole) serving as first-line therapy for most Candida infections and voriconazole as the drug of choice for invasive aspergillosis. 1, 2

Superficial and Mucocutaneous Fungal Infections

Oropharyngeal Candidiasis

• First-line therapy: Fluconazole 100-200 mg/day PO for 7-14 days (1-7 days in children) 1
• Alternatives: Nystatin suspension 200,000-400,000 U PO qid, or itraconazole 200 mg/day 1
• Treatment duration should be at least 2 weeks to decrease likelihood of relapse 3

Esophageal Candidiasis

• First-line therapy: Fluconazole 200-400 mg/day PO for 14-21 days until clinical improvement 1
• Alternatives: Itraconazole 200 mg/day PO, voriconazole, echinocandins, or amphotericin B 0.3-0.7 mg/kg/day IV 1, 2
• Treat for minimum of 3 weeks and at least 2 weeks following resolution of symptoms 3

Vaginal Candidiasis

• Single-dose therapy: Fluconazole 150 mg PO as a single dose 3

Invasive Candida Infections

Candidemia and Disseminated Candidiasis

• First-line therapy: Echinocandins (caspofungin, micafungin, anidulafungin) or fluconazole depending on severity and prior azole exposure 1
• Alternative: Amphotericin B 0.7-1.0 mg/kg/day IV 1
• Treat for at least 14 days following resolution of symptoms or last positive culture, whichever is longer 4
• Critical step: Remove all intravascular catheters when feasible 1

Neonatal Candidiasis

• First-line therapy: Amphotericin B 1.0 mg/kg/day, fluconazole 12 mg/kg/day, or echinocandin 1
• Mandatory workup: Lumbar puncture and ophthalmoscopic examination in all neonates with positive sterile body fluid or urine cultures 1
• Treat for 3 weeks for candidemia without persistent fungemia or metastatic complications 1

CNS Candidiasis

• First-line therapy: Amphotericin B with or without flucytosine (5-FC) 1
• Alternative: Fluconazole 400-800 mg (6-12 mg/kg) daily for patients unable to tolerate amphotericin B 1
• Remove intraventricular devices 1
• Voriconazole can be used as step-down therapy in stable patients 1, 2

Candida Endophthalmitis

• First-line therapy: Amphotericin B 0.7-1 mg/kg with flucytosine 1
• Alternatives: Fluconazole, liposomal amphotericin B, voriconazole, or echinocandin 1, 2
• Duration: at least 4-6 weeks, determined by repeated examinations 1, 2
• Surgical intervention required for severe endophthalmitis or vitreitis 1

Candida Urinary Tract Infections

• Asymptomatic cystitis: Therapy usually not needed; eliminate predisposing factors 1
  • Exception: Treat high-risk surgical patients, neonates, or neutropenic patients as disseminated candidiasis 1
• Symptomatic cystitis: Fluconazole 200 mg (3 mg/kg) daily for 14 days 1
• Pyelonephritis: Fluconazole 200-400 mg (3-6 mg/kg) daily for 14 days 1
  • Alternative: Amphotericin B with or without flucytosine for 7-14 days 1

Invasive Aspergillosis

Primary Treatment

• Drug of choice: Voriconazole is the preferred first-line agent for all forms of invasive aspergillosis 2, 4
• Loading dose: 6 mg/kg IV every 12 hours for 2 doses on Day 1 4
• Maintenance dose: 4 mg/kg IV every 12 hours or 200 mg PO every 12 hours 2, 4
• Alternatives: Liposomal amphotericin B 3 mg/kg/day or echinocandins 1

Site-Specific Considerations

• Pulmonary aspergillosis: Voriconazole with surgical intervention for lesions near great vessels, chest wall invasion, or persistent hemoptysis 1, 2
• CNS aspergillosis: Voriconazole with surgical resection when feasible 1, 2
  • Critical warning: Monitor for drug interactions between voriconazole and anticonvulsants 1
• Chronic cavitary pulmonary aspergillosis: Itraconazole or voriconazole as oral therapy 1, 2

Duration of Therapy

• Treat until resolution or stabilization of all clinical and radiographic manifestations 1
• Median duration in clinical trials: 10 days IV followed by 76 days oral 4
• Reversal of immunosuppression is critical for favorable outcomes 1

Cryptococcal Infections

Cryptococcal Meningitis

• Initial therapy: Amphotericin B 400 mg on Day 1, followed by 200-400 mg once daily 3
• Duration: 10-12 weeks after cerebrospinal fluid becomes culture negative 3
• Maintenance therapy for AIDS patients: Fluconazole 200 mg once daily until CD4 >100/μL and undetectable HIV RNA for 3 months 1
• Start HAART therapy 4-6 weeks after initiating antifungal therapy in AIDS patients 1

Empirical and Pre-emptive Therapy

Empirical Therapy in Neutropenic Patients

• Options: Amphotericin B 0.7-1.0 mg/kg/day IV, echinocandins, or voriconazole 1
• Use voriconazole when additional mold coverage is desired 1
• Critical decision point: Favor amphotericin B for patients at risk of invasive zygomycosis 1, 2

Pre-emptive Therapy

• Initiate based on radiologic studies or laboratory markers (e.g., galactomannan antigen), not fever alone 1
• Favor voriconazole when radiological presentations suggest invasive aspergillosis with positive galactomannan 1

Zygomycosis (Mucormycosis)

Treatment Approach

• Mandatory therapy: Liposomal amphotericin B or amphotericin B deoxycholate 1, 2
• Critical intervention: Aggressive surgical resection of infected tissue is mandatory 1, 2
• Absolute contraindication: Never use voriconazole for zygomycosis 2
• High-dose amphotericin B can be considered when surgery is not feasible 1

Scedosporiosis and Fusariosis

• Indication: Voriconazole for patients intolerant of or refractory to other therapy 4
• Dosing: Same as for invasive aspergillosis 4

Critical Pitfalls to Avoid

• Never delay treatment for culture results in suspected invasive fungal infections; initiate empiric therapy and adjust based on results 1
• Do not use fluconazole for invasive aspergillosis or other mold infections 1
• Avoid voriconazole in patients at risk for zygomycosis; use amphotericin B formulations instead 1, 2
• Always remove intravascular catheters in candidemia when feasible 1
• Monitor for drug interactions with azoles, particularly voriconazole's inhibition of cytochrome P-450 enzymes 5
• Check hepatic function regularly with azole therapy; hepatotoxicity occurs in 1-13% of patients 5
• Ensure adequate treatment duration; inadequate therapy leads to recurrence 3
• Perform susceptibility testing for persistent or recurrent infections 1

Administration Considerations

• Administer voriconazole tablets at least 1 hour before or after meals 4
• Fluconazole has high oral bioavailability; switching between IV and oral formulations is appropriate 3, 4
• For patients weighing <40 kg, reduce oral maintenance doses by half 4