What is the recommended treatment for histoplasmosis?

Treatment of Histoplasmosis

The recommended treatment for histoplasmosis varies by disease type and severity, with amphotericin B formulations used for severe cases followed by itraconazole, while itraconazole alone is appropriate for mild to moderate disease. 1

Treatment Approach Based on Disease Type

Severe Acute Pulmonary Histoplasmosis

• Initial therapy:
  • Lipid formulation of amphotericin B (3.0-5.0 mg/kg daily IV for 1-2 weeks) 1
  • Alternative: Amphotericin B deoxycholate (0.7-1.0 mg/kg daily IV) for patients at low risk for nephrotoxicity 1
• Follow-up therapy:
  • Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily to complete 12 weeks 1
• Adjunctive therapy:
  • Methylprednisolone (0.5-1.0 mg/kg daily IV) during first 1-2 weeks for patients with respiratory complications 1

Mild-to-Moderate Acute Pulmonary Histoplasmosis

• Treatment usually unnecessary 1
• For persistent symptoms >1 month: Itraconazole 200 mg once or twice daily for 6-12 weeks 1

Chronic Cavitary Pulmonary Histoplasmosis

• Itraconazole 200 mg three times daily for 3 days, then once or twice daily for at least 1 year (some prefer 18-24 months due to relapse risk) 1

Progressive Disseminated Histoplasmosis

• Severe disease:
  • Liposomal amphotericin B (3.0 mg/kg daily) for 1-2 weeks 1
  • Then itraconazole 200 mg twice daily for at least 12 months 1
• Mild-to-moderate disease:
  • Itraconazole 200 mg twice daily for at least 12 months 1
• For immunosuppressed patients:
  • Lifelong suppressive therapy with itraconazole 200 mg daily may be required 1

CNS Histoplasmosis (Meningitis)

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

Monitoring During Treatment

Therapeutic Drug Monitoring

• Blood levels of itraconazole should be obtained after at least 2 weeks of therapy 1
• Recommended in cases of:
  • Suspected treatment failure
  • Concerns about compliance or absorption
  • Use of medications that may affect itraconazole metabolism
  • When reducing dose from twice to once daily 1
• Target serum concentration should be >1 μg/mL measured by bioassay 1

Antigen Monitoring

• Antigen levels should be measured during therapy and for 12 months after therapy completion 1
• Therapy should continue until Histoplasma antigen concentrations are <4 units in urine and serum 1

Special Considerations

Potential Pitfalls and Caveats

1. Drug interactions: Itraconazole has numerous drug interactions that can affect efficacy
2. Absorption issues: Itraconazole capsules require gastric acidity for absorption
   • Take with food or cola drinks
   • Avoid antacids, H2 blockers, and proton pump inhibitors 1
3. Hepatotoxicity: Monitor liver enzymes before therapy and at 1,2, and 4 weeks, then every 3 months 1
4. Formulation differences: Itraconazole solution has 30% higher bioavailability than capsules 1

Recent Advances

A 2023 study suggests that a single high dose (10 mg/kg) of liposomal amphotericin B may be effective for HIV/AIDS-related disseminated histoplasmosis, potentially reducing costs and simplifying treatment 2. However, this approach requires further confirmation before becoming standard practice.

Treatment Duration

• Acute pulmonary: 6-12 weeks
• Chronic pulmonary: 12-24 months
• Disseminated (non-AIDS): 6-18 months
• Disseminated (AIDS): Lifelong suppression often required 1

For patients who fail or cannot tolerate itraconazole, fluconazole is an alternative but is less effective, with response rates of approximately 70% compared to higher rates with itraconazole 1.