Cefepime 2g powder for solution for injection vials

There has been increased use of cefepime due to concerns about the nephrotoxic effects of the combined use of vancomycin and Zosyn. However, cefepime is associated with neurotoxicity. We conducted a systematic review using online data to explore the trend of cefepime-induced neurotoxicity over the last 10 years. Forty-six articles met our inclusion criteria, including 73 cases of cefepime-induced neurotoxicity. We noticed a steady increase in the reports of cefepime-induced neurotoxicity, from one case in 2013 to 11 cases in 2022. Individuals aged 65 and older accounted for most cefepime-induced neurotoxicity cases (52%). The top three indications for cefepime administration included bone and joint infections (25%), urinary tract infections (22.7%), and pneumonia (22.7%). Most patients with renal impairment have never had a renal adjustment of their cefepime dosage (either 2 g 12 hours a day or 2 g eight hours a day). Most cases of cefepime-induced neurotoxicity occurred between days two and five (n=29, 71%), while most resolution occurred between days one and five (n=29, 85%). While cefepime continues to be a popularly used and effective antibiotic against gram-negative bacteria like Pseudomonas aeruginosa, its dosage needs to be adjusted in patients with renal impairment to avoid neurotoxicity.

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s of 1 and 4 μg/ml, respectively, representing ≥256- and ≥32-fold improvements, respectively, in antibacterial activity over that of cefepime alone. The data demonstrate the potent, broad-spectrum rescue of cefepime activity by taniborbactam against clinical isolates of CRE and CRPA.

Abstract licence: CC BY

ObjectivesToxic 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 individuals at risk for developing neurotoxic side effects.MethodsRetrospective study including all individuals who underwent cefepime therapeutic drug monitoring (TDM) between 2013 and 2017. Individuals 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, and cerebral and general co-morbidities with the occurrence of neurotoxicity. We also compared the mortality rate during hospitalization in individuals with and without neurotoxicity, and the possible impact of neuroprotective co-medications on outcomes.ResultsCefepime concentrations were determined in 584 individuals. Among 319 individuals with available trough concentrations included, the overall incidence of neurotoxicity was 23.2% (74 of 319 individuals). Higher cefepime plasma trough concentrations were significantly associated with risk of neurotoxicity (no neurotoxicity 6.3 mg/L (interquartile range (IQR) 4.1–8.6) versus with neurotoxicity 21.6 mg/L (IQR 17.0–28.6), p <0.001). Individuals with presumed cefepime neurotoxicity had a significantly lower renal function (estimated glomerular filtration rate 82.0 mL/min/1.73 m2 (IQR 45.0–105.0) versus 35.0 mL/min/1.73 m2 (IQR 23.3–53.3], p <0.001), and significantly higher in-hospital mortality (19 (7.8%) versus 26 (35.1%) individuals, 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 neurological side effects.ConclusionIn individuals with risk factors for cefepime neurotoxicity, such as renal insufficiency, TDM should be systematically performed, aiming at trough concentrations <7.5 mg/L.

Abstract licence: CC BY-NC-ND