Therapeutic drug monitoring of imipenem and the incidence of toxicity and failure in hospitalized patients: a retrospective cohort study. (March 2019)

• Record Type: Journal Article
• Authors: Bricheux, A.; Lenggenhager, L.; Hughes, S.; Karmime, A.; Lescuyer, P.; Huttner, A.
• Is Part Of: Clinical microbiology and infection. Volume 25:Number 3(2019)
• Page Start: 383.e1
• Page End: 383.e4
• Publication Date: 2019-03
• Subjects: Clinical failure -- Imipenem -- Plasma concentrations -- Therapeutic drug monitoring -- Therapeutic range -- Toxicity; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2018.11.020
• Languages: English
• ISSNs: 1198-743X

Abstract

Abstract: 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.