L Boschung-Pasquier1, A Atkinson2, L K Kastner3, S Banholzer3, M Haschke3, N Buetti4, D I Furrer5, C Hauser2, P Jent2, Y A Que6, H Furrer2, B Babouee Flury7. 1. Faculty of Medicine, University of Bern, Bern, Switzerland; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Geriatrics and Rehabilitation, Hôpital Fribourgeois Tavel, Tavel, Switzerland. 2. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. 3. Clinical Pharmacology and Toxicology, Department of General Internal Medicine, Bern University Hospital, University of Bern, Bern, Switzerland. 4. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland; UMR 1137 - IAME Team 5 - DeSCID: Decision SCiences in Infectious Diseases, Control and Care Inserm/University Paris Diderot, Sorbonne Paris Cité, Paris, France. 5. Insel Data Science Center and Insel Data Coordination Lab, Directorate of Teaching and Research, Bern University Hospital, University of Bern, Bern, Switzerland. 6. Department of Intensive Care Medicine, Bern University Hospital, University of Bern, Bern, Switzerland. 7. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: b.baboueeflury@bluewin.ch.
Abstract
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 individuals at risk for developing neurotoxic side effects. METHODS: Retrospective 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. RESULTS: Cefepime 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. CONCLUSION: In individuals with risk factors for cefepime neurotoxicity, such as renal insufficiency, TDM should be systematically performed, aiming at trough concentrations <7.5 mg/L.
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 individuals at risk for developing neurotoxic side effects. METHODS: Retrospective 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. RESULTS:Cefepime 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. CONCLUSION: In individuals with risk factors for cefepime neurotoxicity, such as renal insufficiency, TDM should be systematically performed, aiming at trough concentrations <7.5 mg/L.
Authors: Mohammad H Al-Shaer; Michael N Neely; Jiajun Liu; Kartikeya Cherabuddi; Veena Venugopalan; Nathaniel J Rhodes; Kenneth Klinker; Marc H Scheetz; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2020-08-20 Impact factor: 5.191
Authors: Gwendolyn M Pais; Jack Chang; Erin F Barreto; Gideon Stitt; Kevin J Downes; Mohammad H Alshaer; Emily Lesnicki; Vaidehi Panchal; Maria Bruzzone; Argyle V Bumanglag; Sara N Burke; Marc H Scheetz Journal: Clin Pharmacokinet Date: 2022-06-29 Impact factor: 5.577
Authors: Ashlan J Kunz Coyne; Mohammad Alshaer; Anthony M Casapao; Veena Venugopalan; Carmen Isache; Jason Ferreira; Christopher A Jankowski Journal: Antimicrob Agents Chemother Date: 2022-09-08 Impact factor: 5.938
Authors: Mohammad H Alshaer; Sylvain Goutelle; Barbara A Santevecchi; Bethany R Shoulders; Veena Venugopalan; Kartikeya Cherabuddi; Jiajun Liu; Patrick J Kiel; Jason A Roberts; Fekade Bruck Sime; Marc H Scheetz; Michael N Neely; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2021-12-13 Impact factor: 5.938
Authors: Julia Zimmer; Anka C Röhr; Stefan Kluge; Jonas Faller; Otto R Frey; Dominic Wichmann; Christina König Journal: Antibiotics (Basel) Date: 2021-02-28