TY - JOUR
T1 - Cefepime neurotoxicity
T2 - thresholds and risk factors. A retrospective cohort study
AU - Boschung-Pasquier, L.
AU - Atkinson, A.
AU - Kastner, L. K.
AU - Banholzer, S.
AU - Haschke, M.
AU - Buetti, N.
AU - Furrer, D. I.
AU - Hauser, C.
AU - Jent, P.
AU - Que, Y. A.
AU - Furrer, H.
AU - Babouee Flury, B.
N1 - Publisher Copyright:
© 2019 The Author(s)
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Cefepime
KW - Mortality
KW - Neurotoxicity
KW - Plasma trough concentration
KW - Therapeutic drug monitoring
UR - https://www.scopus.com/pages/publications/85069743753
U2 - 10.1016/j.cmi.2019.06.028
DO - 10.1016/j.cmi.2019.06.028
M3 - Article
C2 - 31284030
AN - SCOPUS:85069743753
SN - 1198-743X
VL - 26
SP - 333
EP - 339
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
IS - 3
ER -