What is the recommended treatment for a confirmed Alternaria infection?

Treatment of Alternaria Species Infections

For confirmed Alternaria infections, voriconazole is the recommended first-line antifungal agent, with itraconazole as an effective alternative, and surgical debridement should be performed for localized cutaneous lesions when feasible.

Primary Antifungal Treatment

First-Line Therapy

• Voriconazole is the preferred agent for Alternaria infections based on clinical success in immunocompromised patients, including complete resolution of cutaneous lesions in transplant recipients who failed amphotericin B therapy 1
• Dosing follows standard protocols: 400 mg (6 mg/kg) IV every 12 hours for two loading doses, then 200 mg (3-4 mg/kg) twice daily, with option to transition to oral therapy once clinical improvement occurs 2, 3
• Voriconazole demonstrated superior efficacy compared to amphotericin B lipid formulations in documented cases of cutaneous alternariosis 1

Alternative Azole Therapy

• Itraconazole 200 mg daily orally is an effective alternative, with documented success in multiple case reports of cutaneous alternariosis 4, 5
• Itraconazole achieved complete resolution in immunocompromised patients (including those on systemic steroids) after 6 weeks of therapy 4
• Fluconazole 200 mg daily may be considered as salvage therapy, though it showed mixed results—ineffective in some cases but successful after prolonged treatment (28 weeks) in chronic granulomatous disease 6, 7

Polyene Therapy

• Lipid formulations of amphotericin B (3-5 mg/kg daily) should be reserved for cases where azoles are contraindicated or not tolerated, though clinical failure has been documented with this class 2, 1
• Amphotericin B deoxycholate is not recommended due to inferior outcomes and significant nephrotoxicity 1

Treatment Duration and Monitoring

• Continue antifungal therapy for 6-12 weeks minimum for invasive or disseminated infections, similar to other dematiaceous mold infections 2
• For localized cutaneous disease, treatment duration of 6 weeks has shown success, though this should extend until complete clinical and radiographic resolution 4
• Treatment must continue until all signs, symptoms, and radiological abnormalities have resolved 2
• Therapeutic drug monitoring is recommended for voriconazole to ensure adequate levels and minimize toxicity 2, 3

Surgical Management

• Surgical debridement of infected tissue is strongly recommended as adjunctive therapy for localized cutaneous lesions 2, 1
• Individual lesions respond well to curettage and cautery or cryotherapy (double freeze-thaw technique) when combined with systemic antifungal therapy 6
• Surgical intervention is particularly important when medical therapy alone shows inadequate response 1

Host Factor Optimization

• Reversal of immunosuppression is critical whenever feasible—this is the most important prognostic factor for successful treatment 2
• Reduce corticosteroid doses if clinically possible, as steroid use is a major predisposing factor for Alternaria infections 4, 5
• Consider delaying or modifying cytotoxic chemotherapy in patients with active infection 2

Special Populations and Considerations

Immunocompromised Hosts

• Alternaria infections occur predominantly in immunocompromised patients (transplant recipients, those on chronic steroids, chronic granulomatous disease, IgA deficiency) 1, 4, 7, 5
• These patients require more aggressive and prolonged therapy compared to immunocompetent hosts 5
• Secondary prophylaxis should be considered in patients requiring ongoing immunosuppression after successful treatment 2

Treatment Failures

• When facing treatment failure, obtain antifungal susceptibility testing, review drug interactions (particularly with anticonvulsants for voriconazole), perform therapeutic drug monitoring, and consider switching to a different antifungal class 2, 3
• Combination therapy has not been well-studied for Alternaria but may be considered in refractory cases based on principles from other mold infections 2

Critical Pitfalls to Avoid

• Do not rely on fluconazole monotherapy as first-line treatment—it has shown inconsistent efficacy and requires prolonged courses when effective 6, 7
• Do not use amphotericin B deoxycholate as first-line therapy given documented treatment failures and toxicity profile 1
• Do not treat without surgical debridement when localized cutaneous lesions are present—medical therapy alone may be insufficient 1, 6
• Do not continue ineffective therapy—if no clinical improvement occurs within 2-3 weeks, switch antifungal agents rather than prolonging an inadequate regimen 6
• Be aware that itraconazole can cause hyperglycemia, particularly relevant in transplant recipients on immunosuppression 6