Treatment of Trichosporon asahii Infections
Voriconazole is the first-line treatment for Trichosporon asahii infections due to its superior antifungal activity against this organism compared to other antifungal agents.
Antifungal Selection Based on Infection Type
Disseminated/Invasive Infections
First-line therapy: Voriconazole 6 mg/kg IV q12h for 2 doses (loading), then 4 mg/kg IV q12h
- Transition to oral therapy (200-300 mg PO BID) when clinically stable
- Duration: Minimum 12 weeks, longer based on clinical response and immune status 1
Alternative therapy: Isavuconazole 200 mg IV/PO q8h for 6 doses, then 200 mg daily 2
If azoles cannot be used: Liposomal amphotericin B 3-5 mg/kg/day IV 3
- Note: Amphotericin B often shows inadequate fungicidal activity against Trichosporon species 1
Localized Infections
- First-line therapy: Voriconazole 200 mg PO BID 4, 5
- Alternative therapy: Itraconazole 200 mg PO BID 1
Evidence-Based Rationale
Trichosporon asahii presents unique treatment challenges due to:
- Intrinsic resistance to echinocandins (completely ineffective) 1
- Poor susceptibility to amphotericin B formulations 1, 6
- Variable response to different azole antifungals 1
A head-to-head comparison study of triazoles against 90 clinical isolates of T. asahii demonstrated that voriconazole has the highest activity against this pathogen, with MIC-90 values of 0.12 μg/ml (MIC-2) and 0.5 μg/ml (MIC-0) 1. By rank order of effectiveness: voriconazole > itraconazole ≈ posaconazole ≈ isavuconazole > fluconazole 1.
Multiple case reports have documented successful treatment of T. asahii infections with voriconazole in:
- Pediatric oncology patients 4
- Immunocompetent children with mastoiditis 5
- Combined liver-kidney transplant recipients 6
Special Considerations
Immunocompromised Patients
- Consider longer treatment duration (>12 weeks)
- Monitor for breakthrough infections
- May require secondary prophylaxis if immunosuppression cannot be reversed
Drug Interactions
- When using voriconazole with calcineurin inhibitors (tacrolimus, cyclosporine), reduce immunosuppressant dose by approximately two-thirds due to significant drug interactions 6
- Monitor drug levels of both voriconazole and immunosuppressants
Therapeutic Drug Monitoring
- Target voriconazole trough levels: 1-5.5 μg/mL
- Obtain levels after 5-7 days of therapy or after dose adjustments
Treatment Failure
If clinical failure occurs with voriconazole:
- Check voriconazole levels to ensure therapeutic concentrations
- Consider switching to isavuconazole, which has shown success in cases where voriconazole was discontinued due to adverse effects 2
- Consider combination therapy (though evidence is limited)
Surgical Considerations
- For localized infections (e.g., mastoiditis, abscesses), surgical debridement should be performed when feasible to reduce fungal burden
Duration of Therapy
- Localized infections: Minimum 4-6 weeks after clinical resolution
- Disseminated/invasive infections: Minimum 12 weeks
- Immunocompromised patients: Consider prolonged therapy until immune reconstitution
The high mortality rate associated with T. asahii infections (up to 80% in some reports) underscores the importance of early diagnosis and prompt initiation of appropriate antifungal therapy 4.