What is the recommended treatment for histoplasmosis?

Treatment of Histoplasmosis

The recommended treatment for histoplasmosis depends on the clinical presentation, with amphotericin B formulations indicated for severe disease followed by itraconazole for step-down therapy, while itraconazole alone is recommended for mild to moderate disease. 1

Treatment Based on Disease Severity

Severe or Moderately Severe Disease

• Lipid formulation of amphotericin B (3.0-5.0 mg/kg daily intravenously) or amphotericin B deoxycholate (0.7-1.0 mg/kg daily) for 1-2 weeks as initial therapy 1
• Follow with itraconazole (200 mg twice daily) to complete a total of 12 weeks of treatment 1
• Liposomal amphotericin B has demonstrated higher response rates (88% vs 64%) and lower mortality (2% vs 13%) compared to amphotericin B deoxycholate in patients with AIDS and progressive disseminated histoplasmosis 1
• Methylprednisolone (0.5-1.0 mg/kg daily intravenously) during the first 1-2 weeks may be beneficial for patients who develop respiratory complications, hypoxemia, or significant respiratory distress 1

Mild to Moderate Disease

• Itraconazole (200 mg once or twice daily for 6-12 weeks) is the preferred treatment 1
• For patients with symptoms lasting less than 4 weeks, treatment may be unnecessary as the condition is often self-limited 1
• Itraconazole solution should be used whenever possible as it has better absorption when given on an empty stomach compared to capsules 1

Treatment Duration Based on Disease Type

Chronic Cavitary Pulmonary Histoplasmosis

• Itraconazole (200 mg once or twice daily) for at least 12 months 1
• Blood levels of itraconazole should be monitored after at least 2 weeks of therapy to ensure adequate drug exposure 1
• Relapse occurs in approximately 15% of cases 1

Progressive Disseminated Histoplasmosis

• For immunocompetent patients: itraconazole for 6-18 months after initial amphotericin B therapy 1
• For AIDS patients: lifelong itraconazole therapy is recommended 1
• Fluconazole (200-800 mg daily) has shown 70% effectiveness in non-AIDS patients with disseminated histoplasmosis but is less effective than itraconazole 1

CNS Histoplasmosis

• Amphotericin B for 3 months, followed by fluconazole for 12 months 1

Special Considerations

Monitoring Therapy

• Hepatic enzyme levels should be measured before starting azole therapy and at 1,2, and 4 weeks, then every 3 months during treatment 1
• Itraconazole blood levels should be monitored in cases of suspected treatment failure, concerns about absorption, drug interactions, or when adjusting dosage 1

Alternative Therapies

• Voriconazole has been associated with increased mortality in the first 42 days compared to itraconazole and is not recommended as first-line therapy 2
• Isavuconazole may be considered in cases where first-line and second-line therapies have failed or are contraindicated, except in meningitis 3

Treatment in Special Populations

• For patients on TNF-α blockers who develop histoplasmosis, discontinuation of immunosuppression is recommended during antifungal treatment 4
• Resumption of TNF-α blocker therapy appears safe after at least 12 months of antifungal therapy and clinical response 4

Common Pitfalls and Caveats

• Itraconazole capsules require high gastric acidity for absorption and should be taken with food or a cola drink 1
• Patients receiving antacids, H2 blockers, or proton pump inhibitors should not use itraconazole capsules due to decreased absorption 1
• Treatment is not indicated for asymptomatic patients with healed histoplasmosis manifestations such as pulmonary nodules, mediastinal lymphadenopathy, or calcified splenic lesions 1
• Presumed ocular histoplasmosis syndrome does not respond to antifungal therapy 1