Favorable effects of voriconazole trough concentrations exceeding 1 µg/mL on treatment success and all-cause mortality: A systematic review and meta-analysis

Yuki Hanai, Yukihiro Hamada, Toshimi Kimura, Kazuaki Matsumoto, Yoshiko Takahashi, Satoshi Fujii, Kenji Nishizawa, Yoshitsugu Miyazaki, Yoshio Takesue

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number306
JournalJournal of Fungi
Volume7
Issue number4
DOIs
Publication statusPublished - 2021 Apr

Keywords

  • Meta-analysis
  • Mortality
  • Therapeutic drug monitoring
  • Trough concentration
  • Voriconazole

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Plant Science
  • Microbiology (medical)

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