What is the treatment for histoplasmosis?

Treatment of Histoplasmosis

Treatment Algorithm Based on Disease Severity

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

Severe Disease Indicators

• Respiratory insufficiency requiring ventilatory support 1
• Hypoxemia or significant respiratory distress 1, 2
• Hemodynamic compromise 1
• Progressive disseminated disease with fever >39.5°C, Karnofsky score <60, alkaline phosphatase >5× normal, or albumin <3 g/dL 3

Liposomal amphotericin B is superior to amphotericin B deoxycholate, demonstrating 88% vs 64% response rates and 2% vs 13% mortality in AIDS patients with disseminated disease. 1, 2 Amphotericin B lipid complex is an acceptable alternative at lower cost. 1

Adjunctive Corticosteroid Therapy

• Add methylprednisolone (0.5-1.0 mg/kg IV daily, maximum 80 mg) during the first 1-2 weeks for patients with respiratory complications or hypoxemia 1, 2
• When corticosteroids are used, concurrent itraconazole is mandatory to prevent progressive infection from corticosteroid-induced immunosuppression 1, 2

Mild to Moderate Disease

Itraconazole (200 mg three times daily for 3 days, then 200 mg once or twice daily for 6-12 weeks) is the treatment of choice for mild to moderate histoplasmosis. 1, 2

When Treatment Can Be Withheld

• Symptoms lasting <4 weeks in immunocompetent patients, as 95% resolve spontaneously within 3 weeks 1, 2
• Asymptomatic pulmonary nodules, mediastinal lymphadenopathy, or calcified splenic lesions 1, 2

When Treatment Is Required Despite Mild Symptoms

• Symptoms persisting >1 month 1, 2
• Any immunocompromised patient, regardless of symptom severity 1, 4
• Patients requiring corticosteroids for inflammatory complications 2

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

Disseminated Histoplasmosis in AIDS

• Amphotericin B formulation for 1-2 weeks, then itraconazole 200 mg twice daily 1
• Lifelong maintenance therapy with itraconazole is mandatory to prevent relapse 1
• Itraconazole 200-400 mg daily achieves ≥90% efficacy for maintenance 1

CNS Histoplasmosis

• Amphotericin B for 3 months, then fluconazole for 12 months 1

Pericarditis

• Nonsteroidal anti-inflammatory agents for mild cases 1
• Prednisone (0.5-1.0 mg/kg daily, maximum 80 mg, tapered over 1-2 weeks) for hemodynamic compromise or unremitting symptoms 1
• Pericardial drainage if hemodynamic compromise present 1
• Add itraconazole (200 mg three times daily for 3 days, then once or twice daily for 6-12 weeks) if corticosteroids are used 1

Critical Monitoring Requirements

Itraconazole Blood Levels

• Measure itraconazole levels after 2 weeks of therapy to ensure adequate drug exposure 1, 2
• Target concentration: ≥1 mg/mL (MIC90 for H. capsulatum is 0.02 mg/mL) 1
• Recheck levels in suspected treatment failure, absorption concerns, drug interactions, or when reducing from twice to once daily dosing 1, 2

Hepatic Monitoring

• Measure hepatic enzymes before starting azole therapy 2
• Recheck at 1,2, and 4 weeks, then every 3 months during treatment 2

Common Pitfalls to Avoid

Itraconazole Absorption Issues

• Itraconazole capsules require high gastric acidity and must be taken with food or cola 2
• Do not use itraconazole capsules in patients taking antacids, H2 blockers, or proton pump inhibitors due to severely impaired absorption 2
• Consider itraconazole solution or alternative agents in these situations 2

Inappropriate Treatment Scenarios

• Do not treat presumed ocular histoplasmosis syndrome—it does not respond to antifungal therapy 1, 2
• Do not treat based solely on positive antibody tests in minimally symptomatic patients, as this may reflect past exposure 2
• Avoid fluconazole as primary therapy—it is less effective than itraconazole (64-74% vs 85-100% response rates) and resistance develops in treatment failures 1

Treatment Failure Recognition

• Patients with moderately severe baseline abnormalities respond more poorly to itraconazole alone and require initial amphotericin B 3
• Fungemia should clear within 1 week; persistent positive cultures indicate treatment failure 3
• Fever should resolve within 1-2 weeks of appropriate therapy 1