Treatment of Histoplasmosis
The treatment of choice for histoplasmosis depends on disease severity, with liposomal amphotericin B recommended for severe disease followed by step-down to itraconazole, while itraconazole alone is recommended for mild to moderate disease. 1
Treatment Algorithm Based on Disease Severity
Severe Disease/Hospitalized Patients
- Initial therapy: Liposomal amphotericin B 3-5 mg/kg IV daily for 1-2 weeks 1
- Step-down therapy: Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily 1
- Total treatment duration: At least 12 weeks 2
- Monitor renal function, electrolytes, complete blood count, and liver function tests daily during amphotericin B therapy 1
Mild to Moderate Disease (Outpatient)
- First-line: Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily for 12 weeks 1
- Alternative (if itraconazole cannot be used): Fluconazole 800 mg daily, but note this has reduced efficacy compared to itraconazole 1
Special Populations
Immunocompromised Patients (including HIV/AIDS)
- Same initial treatment as above based on severity
- Maintenance therapy: Itraconazole 200 mg once or twice daily 2
- Duration: Lifelong suppressive therapy in patients with AIDS or if immunosuppression cannot be reversed 1
- For HIV patients: Can discontinue maintenance therapy if CD4 count increases to ≥150 cells/μL for at least one year 3
- Antiretroviral therapy should be initiated immediately in HIV patients as the risk of immune reconstitution syndrome is low 3
Pregnant Women
- Amphotericin B formulations are preferred due to teratogenicity of azoles 1
Treatment Monitoring
- Antigen levels should be measured during therapy and for 12 months after completion 1
- Continue therapy until Histoplasma antigen concentrations are <4 units in urine and serum 1
- For patients on fluconazole, close clinical monitoring for relapse is essential, with antigen concentrations in urine and blood monitored quarterly 2
Treatment Efficacy
- Itraconazole has shown 85-100% response rates in various studies 2
- Liposomal amphotericin B shows higher response rates (88%) and lower mortality (2%) compared to conventional amphotericin B (response 64%, mortality 13%) 1
- Fluconazole is less effective, with relapse occurring in nearly one-third of patients who received fluconazole maintenance therapy 2
Alternative Options for Treatment Failures
- In cases where first-line and second-line therapies have failed or are contraindicated, isavuconazole may be considered as an alternative (except for meningitis) 4
- This option should be reserved for special circumstances where standard therapies cannot be used
Common Pitfalls and Caveats
- Fluconazole has inferior activity against H. capsulatum compared to itraconazole and should only be used when itraconazole cannot be used 1
- In vitro resistance to fluconazole can develop during treatment 2
- Intravascular device-related complications can occur in up to 63% of patients on long-term amphotericin B therapy 5
- Patients with moderately severe clinical features (fever >39.5°C, Karnofsky score <60, alkaline phosphatase >5 times normal, or albumin <3 g/dL) tend to respond more poorly to itraconazole and may benefit from initial amphotericin B therapy 6
- Amphotericin B should not be used to treat non-invasive fungal infections 7
By following this evidence-based approach to treating histoplasmosis, clinicians can optimize outcomes while minimizing adverse effects, with treatment decisions guided primarily by disease severity and host immune status.