Voriconazole Steady-State Trough Concentrations and Clinical Outcomes in Patients with Talaromycosis.

Abstract

Background: Voriconazole (VRC) has been used as an alternative treatment for talaromycosis. However, there are few studies reporting the VRC plasma concentration in patients with talaromycosis. The purpose of this study was to analyze the correlations between VRC initial steady-state trough concentration and clinical outcomes.

Methods: We prospectively enrolled patients who were diagnosed with talaromycosis and received VRC as initial antifungal treatment regime. Medical information, VRC initial steady-state trough concentration, clinical outcomes and adverse events (AEs) were recorded for analysis.

Results: This study included 69 patients with talaromycosis receiving VRC treatment, including 38 HIV-positive patients and 31 HIV-negative patients. The average age of the HIV-positive patients was 42 years, and that of the HIV-negative patients was 51 years. After 12 weeks of antifungal treatment, 55 patients achieved clinical remission, 3 patients were transferred to amphotericin B treatment because of persistent clinical symptoms, and 5 patients died, 2 patients discontinued VRC treatment due to AEs. Follow up to 6 months, a total of 14 AEs were observed in 12 patients, and 3 patients discontinued VRC treatment due to AEs. The average VRC initial steady-state trough concentration was 5.26 mg/L, with a range of 0.23-16.95 mg/L, indicating high variability. No correlation was found between the VRC initial steady-state trough concentration and treatment failure (P = 0.079). A significant correlation between AEs and the VRC initial steady-state trough concentration was found (P = 0.048). The VRC initial steady-state trough concentration threshold for AEs was 5.88 mg/L according to the ROC curve analysis. In addition, there was a significant correlation between mortality and the APACHE II score (P = 0.029). The risk of death significantly increased when the APACHE II score was > 10.

Conclusion: Voriconazole is an effective antifungal drug for talaromycosis in patients with APACHE II scores < 10. VRC steady-state trough concentration may not be significantly correlated with poor prognosis. A high VRC trough concentration was significantly correlated with AEs, and it may promote the management of AEs.