Cefepime neurotoxicity: thresholds and risk factors. A retrospective cohort study
Cefepime neurotoxicity: thresholds and risk factors. A retrospective cohort study
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DOI：
10.1016/j.cmi.2019.06.028
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发表时间：
2020-03-01
影响因子：
14.2
通讯作者：
Flury, B. Babouee
中科院分区：
文献类型：
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作者：
Boschung-Pasquier, L.;Atkinson, A.;Flury, B. Babouee
目的：目前文献中对头孢吡肟毒血清谷浓度没有很好的定义。我们的目标是为这种抗生素的神经毒性定义一个更精确的血浆谷浓度阈值，并确定有神经毒性副作用风险的个体。方法：回顾性研究，纳入2013 - 2017年所有接受头孢吡肟治疗药物监测（TDM）的患者。排除头孢吡肟浓度低于谷值的个体。主要结果是评估神经毒性的发生率及其与头孢吡肟血浆谷浓度的关系。次要结局是肾功能、头孢吡肟日剂量、年龄、脑和一般合并症与神经毒性发生的关系。我们还比较了有和无神经毒性患者住院期间的死亡率，以及联合使用神经保护药物对预后的可能影响。结果：测定了584例头孢吡肟血药浓度。在319例可获得谷浓度的个体中，神经毒性的总发生率为23.2%（319例中有74例）。较高的头孢吡肟血浆谷浓度与神经毒性风险显著相关(无神经毒性6.3 mg/L（四分位数范围（IQR） 4.1-8.6），而有神经毒性21.6 mg/L (IQR 17.0-28.6), p
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