Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis

Journal of Fungi

卷:7

Yoshitsugu Miyazaki¹  Satoshi Fujii²  Yoshio Takesue³  Yoshiko Takahashi⁴  Kenji Nishizawa⁵  Yuki Hanai⁵  Yukihiro Hamada⁶  Toshimi Kimura⁶  Kazuaki Matsumoto⁷ 

[1] Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo 162-8640, Japan;

[2] Department of Hospital Pharmacy, Sapporo Medical University Hospital, Hokkaido 060-8543, Japan;

[3] Department of Infection Control and Prevention, Hyogo College of Medicine, Hyogo 663-8501, Japan;

[4] Department of Pharmacy, Hyogo College of Medicine, Hyogo 663-8501, Japan;

[5] Department of Pharmacy, Toho University Omori Medical Center, Tokyo 143-8541, Japan;

[6] Department of Pharmacy, Tokyo Women’s Medical University Hospital, Tokyo 162-8666, Japan;

[7] Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo 105-8512, Japan;

关键词: voriconazole;    meta-analysis;    trough concentration;    therapeutic drug monitoring;    mortality;   

DOI  :  10.3390/jof7040306

来源: DOAJ

【 摘 要 】

This systematic review and meta-analysis examined the optimal trough concentration of voriconazole for adult patients with invasive fungal infections. We used stepwise cutoffs of 0.5–2.0 μg/mL for efficacy and 3.0–6.0 μg/mL for safety. Studies were included if they reported the rates of all-cause mortality and/or treatment success, hepatotoxicity, and nephrotoxicity according to the trough concentration. Twenty-five studies involving 2554 patients were included. The probability of mortality was significantly decreased using a cutoff of ≥1.0 μg/mL (odds ratio (OR) = 0.34, 95% confidence interval (CI) = 0.15–0.80). Cutoffs of 0.5 (OR = 3.48, 95% CI = 1.45–8.34) and 1.0 μg/mL (OR = 3.35, 95% CI = 1.52–7.38) also increased the treatment success rate. Concerning safety, significantly higher risks of hepatotoxicity and neurotoxicity were demonstrated at higher concentrations for all cutoffs, and the highest ORs were recorded at 4.0 μg/mL (OR = 7.39, 95% CI = 3.81–14.36; OR = 5.76, 95% CI 3.14–10.57, respectively). Although further high-quality trials are needed, our findings suggest that the proper trough concentration for increasing clinical success while minimizing toxicity is 1.0–4.0 μg/mL for adult patients receiving voriconazole therapy.

【 授权许可】

Unknown