Treatment of Histoplasmosis
For severe or moderately severe histoplasmosis, initiate lipid formulation amphotericin B (3.0-5.0 mg/kg IV daily) or amphotericin B deoxycholate (0.7-1.0 mg/kg IV daily) for 1-2 weeks, then transition to itraconazole (200 mg twice daily) to complete 12 weeks total treatment. 1, 2
Severity-Based Treatment Algorithm
Severe or Moderately Severe Disease
Initial therapy (1-2 weeks):
- Liposomal amphotericin B is superior to amphotericin B deoxycholate, demonstrating 88% vs 64% response rates and 2% vs 13% mortality in AIDS patients with progressive disseminated histoplasmosis 1, 2
- Amphotericin B lipid complex is an acceptable alternative with lower cost 1
- Amphotericin B deoxycholate remains reasonable for patients at low risk for nephrotoxicity 1
Step-down therapy:
- Transition to itraconazole 200 mg twice daily once clinical improvement occurs and oral intake is tolerated 1, 2
- Complete 12 weeks total treatment duration 2
Adjunctive corticosteroids:
- Add methylprednisolone 0.5-1.0 mg/kg IV daily during the first 1-2 weeks for respiratory complications, hypoxemia, or significant respiratory distress 1, 2
Mild to Moderate Disease
Itraconazole monotherapy is the preferred treatment:
- Dosing: 200 mg three times daily for 3 days (loading), then 200 mg once or twice daily for 6-12 weeks 1, 2
- This approach avoids amphotericin B toxicity in patients who can tolerate oral therapy 3
Self-Limited Acute Pulmonary Histoplasmosis
No treatment is necessary for:
- Symptoms lasting <1 month in immunocompetent patients 1, 2
- 95% of cases resolve within 3 weeks without intervention 1, 2
Treat only if:
Disease-Specific Treatment Durations
Chronic Cavitary Pulmonary Histoplasmosis
- Itraconazole 200 mg once or twice daily for at least 12 months (some prefer 18-24 months due to 15% relapse risk) 1, 2
Progressive Disseminated Histoplasmosis
- Amphotericin B formulation for 1-2 weeks, then itraconazole for 12 weeks minimum 2
- AIDS patients require lifelong suppressive therapy 1
Inflammatory Complications
Pericarditis:
- Mild cases: NSAIDs alone 1
- Severe cases with hemodynamic compromise: prednisone 0.5-1.0 mg/kg daily (max 80 mg) tapered over 1-2 weeks PLUS itraconazole 200 mg once or twice daily for 6-12 weeks 1
- Pericardial drainage if hemodynamic compromise present 1
Mediastinal lymphadenitis:
- Usually no treatment needed 1
- If corticosteroids required for obstruction: add itraconazole 200 mg once or twice daily for 6-12 weeks to prevent progressive disseminated disease 1, 2
Critical Monitoring Requirements
Itraconazole blood levels:
- Measure after 2 weeks of therapy to ensure adequate drug exposure 1, 2
- Recheck with suspected treatment failure, absorption concerns, or drug interactions 2
Hepatic monitoring:
- Measure hepatic enzymes before starting azole therapy 2
- Recheck at weeks 1,2, and 4, then every 3 months during treatment 2
Common Pitfalls to Avoid
Itraconazole absorption issues:
- Capsules require high gastric acidity—take with food or cola 2
- Do not use itraconazole capsules in patients on antacids, H2 blockers, or proton pump inhibitors due to severely impaired absorption 2
- Consider itraconazole oral solution in these patients 2
Avoid treating conditions that do not respond:
- Asymptomatic pulmonary nodules, calcified mediastinal lymphadenopathy, or splenic lesions do not require treatment 1, 2
- Presumed ocular histoplasmosis syndrome does not respond to antifungal therapy 1, 2
Voriconazole should be avoided:
- Recent data shows voriconazole increases mortality in the first 42 days compared to itraconazole (HR 4.30,95% CI 1.3-13.9) 4
- Voriconazole is not recommended despite in vitro activity 4
Fluconazole is inferior: