Therapeutic drug monitoring of imipenem and the incidence of toxicity and failure in hospitalized patients: a retrospective cohort study

Objectives: Therapeutic drug monitoring (TDM) of beta-lactam antibiotics is increasingly employed to ensure adequate antibiotic exposure and slow emergence of resistance. Imipenem's therapeutic range has not been defined; we report plasma concentrations and clinical outcomes of patients receiving imipenem for bacterial infections. Methods: All hospitalized adult patients undergoing imipenem TDM during therapy for suspected or confirmed bacterial infections between 1 January 2013 and 28 February 2017 were included in this single-centre retrospective cohort. The primary outcome was incidence of clinical toxicity; secondary outcomes included incidence of clinical failure and median imipenem concentrations in those with and without toxicity and/or failure. Total imipenem concentrations were measured via high-performance liquid chromatography with ultraviolet detection. Results: A total of 403 imipenem levels were drawn from 300 patients. Fifteen (5%) patients experienced an adverse event considered at least possibly related to imipenem. Eighty-eight (29%) patients had clinical failure; augmented renal clearance appeared to emerge as a protective factor against failure (OR 0.42; 95% CI 0.20-0.89). Median first-measure trough concentration was 3.2 mg/L (IQR 1.7-6.5). Patients with suspected toxicity did not have higher concentrations. Patients whose dose was not increased after a trough level < 2 mg/L was returned trended towards increased clinical failure (3/28 (11%) vs. 12/63 (19%)), though the difference was not statistically significant. Conclusions: Toxicity was rare and clinical failure frequent in this cohort of patients whose imipenem concentrations were generally low and occasionally undetectable. Larger trials are needed to define optimal imipenem exposure. (c) 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.