Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study

摘要

Abstract BackgroundAugmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).MethodsIn this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before ( Control period ) and after ( Treatment period ) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥?150?ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28?days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.ResultsDuring the study period, 177 patients were included ( control period , N =?88; treatment period , N =?89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p?=?0.019 ). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15–0.81), p?=?0.014 . No antibiotic side effect was reported during the treatment period.ConclusionsHigher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.