Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis
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 mo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/7/4/306 |
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| author | Yuki Hanai Yukihiro Hamada Toshimi Kimura Kazuaki Matsumoto Yoshiko Takahashi Satoshi Fujii Kenji Nishizawa Yoshitsugu Miyazaki Yoshio Takesue |
| author_facet | Yuki Hanai Yukihiro Hamada Toshimi Kimura Kazuaki Matsumoto Yoshiko Takahashi Satoshi Fujii Kenji Nishizawa Yoshitsugu Miyazaki Yoshio Takesue |
| author_sort | Yuki Hanai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:15:15Z |
| format | Article |
| id | doaj.art-425b65656b4c4b4a85817eebe389c025 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-10T12:15:15Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-425b65656b4c4b4a85817eebe389c0252023-11-21T15:54:57ZengMDPI AGJournal of Fungi2309-608X2021-04-017430610.3390/jof7040306Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-AnalysisYuki Hanai0Yukihiro Hamada1Toshimi Kimura2Kazuaki Matsumoto3Yoshiko Takahashi4Satoshi Fujii5Kenji Nishizawa6Yoshitsugu Miyazaki7Yoshio Takesue8Department of Pharmacy, Toho University Omori Medical Center, Tokyo 143-8541, JapanDepartment of Pharmacy, Tokyo Women’s Medical University Hospital, Tokyo 162-8666, JapanDepartment of Pharmacy, Tokyo Women’s Medical University Hospital, Tokyo 162-8666, JapanDivision of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo 105-8512, JapanDepartment of Pharmacy, Hyogo College of Medicine, Hyogo 663-8501, JapanDepartment of Hospital Pharmacy, Sapporo Medical University Hospital, Hokkaido 060-8543, JapanDepartment of Pharmacy, Toho University Omori Medical Center, Tokyo 143-8541, JapanDepartment of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo 162-8640, JapanDepartment of Infection Control and Prevention, Hyogo College of Medicine, Hyogo 663-8501, JapanThis 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.https://www.mdpi.com/2309-608X/7/4/306voriconazolemeta-analysistrough concentrationtherapeutic drug monitoringmortality |
| spellingShingle | Yuki Hanai Yukihiro Hamada Toshimi Kimura Kazuaki Matsumoto Yoshiko Takahashi Satoshi Fujii Kenji Nishizawa Yoshitsugu Miyazaki Yoshio Takesue 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 voriconazole meta-analysis trough concentration therapeutic drug monitoring mortality |
| title | Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis |
| title_full | Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis |
| title_fullStr | Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis |
| title_short | Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis |
| title_sort | favorable effects of voriconazole trough concentrations exceeding 1 μg ml on treatment success and all cause mortality a systematic review and meta analysis |
| topic | voriconazole meta-analysis trough concentration therapeutic drug monitoring mortality |
| url | https://www.mdpi.com/2309-608X/7/4/306 |
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