Utility of voriconazole therapeutic drug monitoring: a meta-analysis
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
PubMed
27165788
DOI
10.1093/jac/dkw099
PII: dkw099
Knihovny.cz E-resources
- MeSH
- Antifungal Agents adverse effects blood therapeutic use MeSH
- Invasive Fungal Infections drug therapy prevention & control MeSH
- Humans MeSH
- Drug Monitoring * MeSH
- Mycoses drug therapy MeSH
- Voriconazole adverse effects blood therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antifungal Agents MeSH
- Voriconazole MeSH
BACKGROUND: Voriconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of voriconazole TDM to guide therapy remains uncertain and controversial. We conducted a meta-analysis of studies assessing the relationship between voriconazole serum concentration and clinical outcomes of success and toxicity. METHODS: We searched bibliographic databases for studies on voriconazole serum concentrations and clinical outcomes. We compared success outcomes between patients with therapeutic and subtherapeutic voriconazole serum concentrations, and toxicity outcomes between patients with and without supratherapeutic serum concentrations. RESULTS: Twenty-four studies were analysed. Pooled analysis for efficacy endpoint demonstrated that patients with therapeutic voriconazole serum concentrations (1.0-2.2 mg/L) were more likely to have successful outcomes compared with those with subtherapeutic voriconazole serum concentrations (OR 2.30; 95% CI 1.39-3.81). A therapeutic threshold of 1.0 mg/L was most predictive of successful outcome (OR 1.94; 95% CI 1.04-3.62). Patients with therapeutic concentrations did not have better survival rates. Pooled analysis for toxicity endpoint demonstrated that patients with supratherapeutic voriconazole serum concentrations (4.0-6.0 mg/L) were at increased risk of toxicity (OR 4.17; 95% CI 2.08-8.36). A supratherapeutic threshold of 6.0 mg/L was most predictive of toxicity (OR 4.60; 95% CI 1.49-14.16). CONCLUSIONS: Patients with therapeutic voriconazole serum concentrations were twice as likely to achieve successful outcomes. The likelihood of toxicity associated with supratherapeutic voriconazole serum concentrations was 4-fold that of therapeutic concentrations. Our findings suggest that the use of voriconazole TDM to aim for serum concentrations between 1.0 and 6.0 mg/L during therapy may be warranted to optimize clinical success and minimize toxicity.
Department of Haematology and Oncology Graduate School of Medicine The University of Tokyo Japan
Division of Infectious Diseases Department of Medicine University of Pittsburgh Pittsburgh PA USA
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