title: Utility of voriconazole therapeutic drug monitoring: a meta-analysis.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Infectious Diseases and Medical Microbiology, Centre Universitaire de l'Université de Montréal (CHUM), University of Montréal, Montréal, Quebec, Canada me-linh.luong.chum@ssss.gouv.qc.ca.
authors.forename: Me-Linh
authors.initials: ML
authors.lastname: Luong
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada Department of Pediatric, Division of Infectious Diseases, King AbdulAziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Jeddah. Saudi Arabia.
authors.forename: Mona
authors.initials: M
authors.lastname: Al-Dabbagh
authors.affiliation: Infectious Disease Research Program, Centre for Bone Marrow Transplantation and Department of Pediatric Haematology/Oncology, University Children's Hospital Münster, Münster, Federal Republic of Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Groll
authors.affiliation: Department of Internal Medicine-Haematology and Oncology, University Hospital Brno, Masaryk University, Brno, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Racil
authors.affiliation: Department of Haematology and Oncology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nannya
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Mitsani
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada.
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D016903:Drug Monitoring; D006801:Humans; D000072742:Invasive Fungal Infections / Q000188:drug therapy* / Q000517:prevention & control; D009181:Mycoses / Q000188:drug therapy*; D016896:Treatment Outcome; D065819:Voriconazole / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole