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Cefepime plasma concentrations and clinical toxicity: a retrospective cohort study.
Clin Microbiol Infect. 2017 Jan 19;:
Authors: Huwyler T, Lenggenhager L, Abbas M, Lorenzini KI, Hughes S, Huttner B, Karmime A, Uçkay I, von Dach E, Lescuyer P, Harbarth S, Huttner A
Abstract
OBJECTIVES: Cefepime remains an important antibiotic for severe bacterial infections, yet some meta-analyses have shown elevated mortality among patients randomised to it. Therapeutic drug monitoring (TDM) of β-lactam antibiotics is increasing, but optimal plasma concentrations remain unknown. We examined clinical outcomes of patients undergoing cefepime TDM in an initial effort to define the drug's toxicity threshold.
METHODS: In this single-centre retrospective cohort study, we enrolled all adult hospitalised patients receiving cefepime and undergoing TDM from January 2013 through July 2016. The primary outcome was the incidence of clinical toxicity; a secondary outcome was clinical failure. Plasma samples were analysed via high-performance liquid chromatography with ultraviolet detection.
RESULTS: A total of 161 cefepime concentrations were drawn from 93 patients. Roughly half (82/161, 51%) and one third (49/161, 30%) were trough and steady-state levels from patients receiving intermittent and continuous infusions, respectively; median concentrations were 17.6 mg/l (IQR 9.7-35.2) and 29.2 mg/l (IQR 18.9-45.9). Ten patients (11%) experienced a neurologic event considered at least possibly related to cefepime; neurotoxicity was associated with poorer renal function (median creatinine clearance 54 [IQR 39-97] vs 75 ml/min/1.73(2) [IQR 44-104]) and longer cefepime durations (mean 8.3 [SD ±6.7] vs 13.3 days [±14.2], P=.071). Patients with trough levels >20 mg/l had a fivefold higher risk for neurologic events (odds ratio 5.05, 95%CI 1.3-19.8).
CONCLUSIONS: Neurotoxicity potentially related to cefepime occurred at plasma concentrations >35 mg/l. For those receiving intermittent infusions, trough concentrations >20 mg/l should be avoided until further information is available from prospective studies.
PMID: 28111294 [PubMed - as supplied by publisher]