Histoplasmosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Medical Therapy

Antifungal medications are used to treat severe cases of acute histoplasmosis and all cases of chronic and disseminated disease. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole. In many milder cases, simply itraconazole is sufficient. Asymptomatic disease is typically not treated. Past infection results in partial protection against ill effects if reinfected.

Antimicrobial Regimen

• Histoplasmosis

• Acute pulmonary histoplasmosis

• Moderately severe or severe

• Preferred regimen: Lipid amphotericin B (Lipid AmB) 3.0–5.0 mg/kg daily for 1–2 weeks OR Amphotericin B deoxycholate 0.7–1.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg 3 times daily for 3 days and then 200 mg twice daily, for a total of 12 weeks
• Note: Methylprednisolone 0.5–1.0 mg/kg daily IV during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress.

• Mild to moderate

• Preferred regimen:

• For symptoms of <4 weeks, none
• For symptoms of >4 weeks, Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks

• Chronic cavitary pulmonary histoplasmosis

• Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then once or twice daily for at least 1 year

• Pericarditis

• Moderately severe to severe

• Preferred regimen(1): Prednisone 0.5–1.0 mg/kg daily (maximum, 80 mg daily) in tapering doses over 1–2 weeks
• Note(1): Itraconazole 200 mg PO 3 times daily for 3 days and then once or twice daily for 6–12 weeks is recommended if corticosteroids are administered
• Note(2): Tamponade requires drainage of pericardial fluid
• Note(3): Antifungal therapy is given to reduce possible dissemination caused by prednisone induced immunosuppression

• Mild

• Preferred regimen: Nonsteroidal anti-inflammatory agents

• Rheumatologic histoplasmosis

• severe

• Preferred regimen: Prednisone 0.5–1.0 mg/kg daily (maximum, 80 mg daily) in tapering doses over 1–2 weeks is recommended in severe cases
• Note: Itraconazole 200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks is recommended if corticosteroids are administered

• Mild

• Preferred regimen: Nonsteroidal anti-inflammatory agents
• Note: Corticosteroids are rarely needed

• Mediastinal lymphadenitis

• Mild symptoms of <4 weeks

• Preferred regimen: None

• Symptoms of >4 weeks

• Preferred regimen: Itraconazole 200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks

• Symptoms warranting treatment

• Preferred regimen: Prednisone 0.5–1.0 mg/kg daily in tapering doses over 1–2 weeks AND Itraconazole 200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks

• Mediastinal granuloma

• Asymptomatic

• Preferred regimen: None

• Symptomatic

• Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks

• Mediastinal fibrosis

• Preferred regimen: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
• Note(1): Antifungal treatment is not recommended
• Note(2): Itraconazole 200 mg PO once or twice daily for 12 weeks is recommended if clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma

• Broncholithiasis

• Preferred regimen: Antifungal treatment is not recommended
• Bronchoscopic or surgical removal of the broncholith is recommended

• Pulmonary Nodules (Histoplasmomas)

• Preferred regimen: Antifungal treatment is not recommended
• Note: Must be differentiated from malignancy

• Progressive disseminated histoplasmosis

• Moderately severe to severe

• Preferred regimen: Liposomal amphotericin B 3.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months
• Alternative regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months
• Note: Longer treatment may be required in patients with persistent immunodeficiency

• Mild to moderate

• Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then twice daily for at least 12 months.
• Note: Longer treatment may be required in patients with persistent immunodeficiency.

• CNS histoplasmosis

• Preferred regimen: Liposomal amphotericin B 5.0 mg/kg daily for a total of 175 mg/kg given over 4–6 weeks followed by Itraconazole 200 mg PO 2 or 3 times daily for at least 12 months and until resolution of CSF abnormalities, including Histoplasma antigen levels.
• Note: Blood levels of itraconazole should be obtained to ensure adequate drug exposure