Boschung-Pasquier, Léna; Atkinson, Andrew; Kastner, Leonie Kassandra; Banholzer, Sarah; Haschke, Manuel; Buetti, Niccolò; Furrer, Dominique I; Hauser, Christoph; Jent, Philipp; Que, Yok-Ai; Furrer, Hansjakob; Babouee Flury, Baharak (2020). Cefepime neurotoxicity: thresholds and risk factors. A Retrospective Cohort study. Clinical microbiology and infection, 26(3), pp. 333-339. Elsevier 10.1016/j.cmi.2019.06.028
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OBJECTIVES
Toxic serum cefepime trough concentrations are not well defined in the current literature. We aimed to define a more precise plasma trough concentration threshold for this antibiotic's neurological toxicity and to identify patients at risk for developing neurotoxic side effects.
METHODS
Retrospective study including all patients who underwent cefepime therapeutic drug monitoring (TDM) between 2013 and 2017. Patients with cefepime concentrations other than trough were excluded. The primary outcome was to assess the incidence of neurotoxicity and its relationship with cefepime plasma trough concentrations. Secondary outcomes were the relationship of renal function, cefepime daily dose, age, cerebral and general comorbidities with the occurrence of neurotoxicity. We also compared the mortality rate during hospitalisation in patients with and without neurotoxicity, and the possible impact of neuroprotective co-medications on the outcomes.
RESULTS
Cefepime concentrations were determined in 584 patients. Among 319 patients with available trough concentrations included, the overall incidence of neurotoxicity was 23.2% (74 of 319 patients). Higher cefepime plasma trough concentrations were significantly associated with risk of (no neurotoxicity 6.3 mg/L [IQR 4.1, 8.6] vs with neurotoxicity 21.6 mg/L [IQR 17.0, 28.6], p <0.001). Patients with presumed cefepime neurotoxicity had a significantly lower renal function (eGFR 82.0 ml/min/1.73m [IQR 45.0, 105.0] vs 35.0 ml/min/1.73m [IQR 23.3, 53.3], p<0.001), and significantly higher in-hospital mortality (19 (7.8%) vs 26 (35.1%) patients, p<0.001).No neurotoxic side effects were seen below a trough concentration of 7.7 mg/L. Levels ≥ 38.1 mg/L always led to neurologic side effects.
CONCLUSION
In patients with risk factors for cefepime neurotoxicity, such as renal insufficiency, TDM should be systematically performed, aiming at trough concentrations below 7.5 mg/L.
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