Treatment of Trichosporon asahii UTI in Patients with AKI
Recommended Antifungal Agent
Voriconazole is the preferred antifungal for treating Trichosporon asahii urinary tract infections, particularly in patients with acute kidney injury, as it demonstrates the highest in vitro activity against this pathogen and achieves adequate urinary concentrations while avoiding the nephrotoxicity of amphotericin B. 1, 2, 3
Rationale for Voriconazole Selection
Voriconazole exhibits superior fungistatic activity against T. asahii compared to all other triazoles, with MIC-0 values of 0.5 μg/ml and MFC values of 2 μg/ml at 48 hours, demonstrating the lowest concentration at which killing activity begins 2
Amphotericin B must be avoided in patients with AKI because KDIGO guidelines strongly recommend using azole antifungals or echinocandins rather than conventional amphotericin B when equal therapeutic efficacy can be assumed (1A recommendation), and T. asahii displays intrinsic resistance to echinocandins 1, 4
Liposomal amphotericin B formulations, while less nephrotoxic than conventional amphotericin B, frequently display inadequate fungicidal activity against Trichosporon species and should be reserved only when azoles cannot be used 2, 3
Dosing and Administration
Standard voriconazole dosing: Loading dose of 6 mg/kg IV every 12 hours for 2 doses, followed by maintenance of 4 mg/kg IV every 12 hours, with transition to oral therapy (200 mg twice daily) once clinically stable 3, 5
No renal dose adjustment is required for voriconazole in AKI, as it is primarily hepatically metabolized; however, the intravenous formulation contains cyclodextrin that accumulates in renal impairment, so switch to oral voriconazole when creatinine clearance is <50 ml/min 3
Monitor voriconazole trough levels targeting 1–5.5 μg/ml due to significant interpatient pharmacokinetic variability and potential drug interactions 3, 4
Alternative Triazole Options
Isavuconazole (loading dose 200 mg IV every 8 hours for 6 doses, then 200 mg daily) represents a valuable alternative when voriconazole causes severe side effects (visual disturbances, hepatotoxicity, QT prolongation), with similar spectrum but fewer drug interactions 4
Posaconazole (300 mg IV/oral twice daily on day 1, then 300 mg daily) demonstrates comparable activity to voriconazole (MIC-0 of 2 μg/ml, MFC of 4 μg/ml) and may be considered when voriconazole is not tolerated 2
Itraconazole (200 mg IV twice daily for 2 days, then 200 mg daily) shows moderate activity (MIC-0 of 2 μg/ml, MFC of 8 μg/ml) but has complex pharmacokinetics and requires acidic environment for absorption, limiting its utility 2
Fluconazole should be avoided as it exhibits the poorest activity against T. asahii (MIC-0 of 32 μg/ml, MFC of 64 μg/ml), requiring concentrations not achievable in serum 2, 5
Treatment Duration and Monitoring
Treat for 14 days minimum for complicated UTI with fungemia, extending to 21–28 days if upper tract involvement (pyelonephritis) is documented or if the patient has persistent immunosuppression 3, 5
Obtain urine culture before initiating therapy and repeat cultures at 72 hours to document microbiological response, as treatment failure may necessitate combination therapy or alternative agents 1, 6
Address underlying urological abnormalities including urinary obstruction, indwelling catheters, or vesicoureteral reflux, as antimicrobial therapy alone is insufficient without source control 6
Replace urinary catheters that have been in place ≥2 weeks at treatment initiation to accelerate symptom resolution and reduce recurrence risk 6
Critical Management Considerations in AKI
Avoid aminoglycosides entirely in AKI patients, as KDIGO guidelines recommend against their use unless no suitable less nephrotoxic alternatives are available (2A recommendation) 1
Monitor for drug interactions when using voriconazole, particularly with tacrolimus (reduce immunosuppressant dose to one-third), warfarin, statins, and proton pump inhibitors 3
Assess renal function serially during voriconazole therapy, as the IV formulation's cyclodextrin vehicle can accumulate; transition to oral formulation when feasible 3
Common Pitfalls to Avoid
Do not use echinocandins (caspofungin, micafungin, anidulafungin) for T. asahii infections, as this genus exhibits intrinsic resistance with no meaningful antifungal effect 2, 4
Do not treat asymptomatic candiduria or Trichosporon colonization in catheterized patients, as this promotes antimicrobial resistance without clinical benefit 1, 6
Do not assume all triazoles are equivalent—voriconazole demonstrates 4–8 fold greater activity than fluconazole and should be prioritized 2, 5
Do not overlook biofilm formation on urinary catheters, as biofilm-forming T. asahii cells are at least 1,000 times more resistant to antifungals than planktonic cells, necessitating catheter removal 7
Special Populations
In elderly patients with urinary drainage devices, T. asahii represents an emerging pathogen requiring prompt recognition and treatment with voriconazole, as this population demonstrates increased susceptibility to invasive infection 5
In immunocompromised hosts (transplant recipients, hematologic malignancies, neutropenia), disseminated infection carries high mortality; early initiation of voriconazole or isavuconazole is critical for survival 3, 4