Utility of posaconazole therapeutic drug monitoring and assessment of plasma concentration threshold for effective prophylaxis of invasive fungal infections: a meta-analysis with trial sequential analysis

Abstract

BackgroundPosaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of posaconazole TDM and the target of posaconazole plasma concentration for clinical successful prophylaxis remain uncertain and controversial. The aim of this study was to evaluate posaconazole exposure-response relationship and determine an optimum posaconazole concentration for prophylaxis against invasive fungal infections (IFIs).MethodsBibliographic databases were searched (from inception to September 2017) to select studies including the clinical outcomes below and above concentration cut-off value of 0.5 mg/L and 0.7 mg/L. The reliability of the results were evaluated with trial sequential analysis (TSA).ResultsTwenty-eight studies with 1930 patients included were analyzed. The results of our pooled analysis demonstrated that patients with posaconazole plasma concentrations over 0.5 mg/L were twice more likely to achieve successful responses compared with those with lower concentrations (odds ratio, OR = 1.98, 95% confidence interval, CI 1.09–3.58, P = 0.02) while the threshold, 0.7 mg/L showed no significant difference (OR = 1.84, 95% CI 0.94–3.63, P = 0.08). The TSA results showed that there was sufficient information to support these findings.ConclusionsAn optimal posaconazole concentration target of 0.5 mg/L is suggested to ensure the clinical prophylactic efficacy and may help reduce the dosage and dose-dependent toxicity comparing with the target of 0.7 mg/L.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3055-3) contains supplementary material, which is available to authorized users.

Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study

“…A serum level of PCZ > 0.70 µg/ml is normally the target concentration for effective prophylaxis (Maleki et al, 2018). A meta-analysis of 28 studies that involved 1,930 patients found that patients with PCZ serum concentrations >0.5 mg/L were twice as likely to achieve successful responses compared to those with lower concentrations (Chen et al, 2018). In our study, a cutoff concentration value of 0.47 µg/ml is recommended, which provides a critical evaluating index for PCZ prophylaxis during the TDM process in China.…”

Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper#

“…Higher C min (> 0.5-0.7 mg/L) has been associated with reduced breakthrough infections in patients receiving posaconazole prophylaxis [143][144][145][146][147][148][149][150]. Patients with invasive aspergillosis demonstrated improved clinical response with an average posaconazole concentration of > 1 mg/L [151,152].…”

Pharmacokinetics and Pharmacodynamics of Posaconazole

“…Thus, C min is also frequently used for TDM measures in practice and considered as a more conservative and practicable index [30,97]. A recent metaanalysis indicated that a C min of 0.5 mg/L could represent a clear margin separating successful from failed prophylaxis [98].…”