Department of Infectious Diseases, Nantes University Hospital and CIC 1413, INSERM, Nantes, France.
EA 3826, University of Nantes, Nantes, France.
J Antimicrob Chemother. 2019 Apr 1;74(4):1078-1085. doi: 10.1093/jac/dky553.
Ceftriaxone is widely used to treat community-acquired CNS bacterial infections. French guidelines for meningitis in adults promote 75-100 mg/kg/day ceftriaxone without an upper limit for dosage, yet little is known about the pharmacology and tolerability of such regimens.
A multicentre prospective cohort study was conducted in adult patients to assess the adverse drug reactions (ADRs) of high-dose ceftriaxone (i.e. daily dosage ≥4 g or ≥75 mg/kg) in CNS infections and to analyse their related factors. Drug causality was systematically assessed by an expert committee who reviewed the medical charts of all included patients.
A total of 196 patients were enrolled over a 31 month period. Median dosage and duration of ceftriaxone were 96.4 mg/kg/day (7 g/day) and 8 days, respectively. Nineteen ceftriaxone-related ADRs (mainly neurological) occurred in 17 patients (8.7%), with only one case of treatment discontinuation (biliary pseudolithiasis). In univariate analysis, older age, male gender, renal impairment and high trough ceftriaxone plasma concentration were associated with ceftriaxone-related ADRs.
High-dose ceftriaxone for CNS infection administered as recommended by French guidelines in adults was well tolerated overall, suggesting these recommendations could be applied and generalized. In patients with advanced age or renal insufficiency, prescription should be done with caution and therapeutic drug monitoring could be useful.
头孢曲松广泛用于治疗社区获得性中枢神经系统细菌感染。法国成人脑膜炎指南推荐使用 75-100mg/kg/天的头孢曲松，且无最高剂量限制，但对于此类方案的药物代谢动力学和耐受性知之甚少。
一项多中心前瞻性队列研究在成人中枢神经系统感染患者中进行，旨在评估高剂量头孢曲松（即每日剂量≥4g 或≥75mg/kg）的不良反应（ADR），并分析其相关因素。药物相关性由专家委员会通过审查所有纳入患者的病历进行系统评估。
在 31 个月的时间里，共纳入 196 例患者。头孢曲松的中位剂量和疗程分别为 96.4mg/kg/天（7g/天）和 8 天。17 例患者（8.7%）发生了 19 例与头孢曲松相关的 ADR（主要为神经系统），仅 1 例因治疗中断（假性胆石症）。单因素分析显示，年龄较大、男性、肾功能不全和较高的头孢曲松血药谷浓度与头孢曲松相关的 ADR 相关。
按照法国指南推荐的剂量，用于成人中枢神经系统感染的高剂量头孢曲松总体耐受性良好，这表明这些推荐可以应用和推广。对于年龄较大或肾功能不全的患者，应谨慎处方，并可能需要进行治疗药物监测。
