Department of Infectious Disease, Centre for Antimicrobial Optimisation, Imperial College London, Hammersmith Hospital, Du Cane Road, UK.
Department of Infectious Disease, National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, Hammersmith Campus, Du Cane Road, UK.
J Antimicrob Chemother. 2022 Nov 28;77(12):3408-3413. doi: 10.1093/jac/dkac332.
Bacterial central nervous system (CNS) infection is challenging to treat and carries high risk of recurrence, morbidity, and mortality. Low CNS penetration of antibiotics may contribute to poor clinical outcomes from bacterial CNS infections. The current application of therapeutic drug monitoring (TDM) to management of bacterial CNS infection was reviewed.
Studies were included if they described adults treated for a suspected/confirmed bacterial CNS infection and had antibiotic drug concentration(s) determined that affected individual treatment.
One-hundred-and-thirty-six citations were retrieved. Seventeen manuscripts were included describing management of 68 patients. TDM for vancomycin (58/68) and the beta-lactams (29/68) was most common. Timing of clinical sampling varied widely between studies and across different antibiotics. Methods for setting individual PK-PD targets, determining parameters and making treatment changes varied widely and were sometimes unclear.
Despite increasing observational data showing low CNS penetration of various antibiotics, there are few clinical studies describing practical implementation of TDM in management of CNS infection. Lack of consensus around clinically relevant CSF PK-PD targets and protocols for dose-adjustment may contribute. Standardised investigation of TDM as a tool to improve treatment is required, especially as innovative drug concentration-sensing and PK-PD modelling technologies are emerging. Data generated at different centres offering TDM should be open access and aggregated to enrich understanding and optimize application.
细菌性中枢神经系统（CNS）感染的治疗具有挑战性，且复发、发病和死亡率高。抗生素对 CNS 的穿透率低可能导致细菌性 CNS 感染的临床结局不佳。本文回顾了治疗药物监测（TDM）在细菌性 CNS 感染管理中的应用。
如果研究描述了接受疑似/确诊细菌性 CNS 感染治疗的成年人，且抗生素药物浓度（s）影响个体治疗，则将其纳入研究。
共检索到 136 篇参考文献。有 17 篇文献描述了 68 例患者的管理情况。万古霉素（58/68）和β-内酰胺类（29/68）的 TDM 最为常见。临床采样的时间在不同研究和不同抗生素之间差异很大。确定个体药代动力学-药效学（PK-PD）目标、参数和治疗调整的方法差异很大，有时也不明确。
尽管越来越多的观察性数据表明各种抗生素对 CNS 的穿透率低，但很少有临床研究描述 TDM 在 CNS 感染管理中的实际应用。缺乏与临床相关的 CSF PK-PD 目标和剂量调整方案的共识可能是造成这种情况的原因。需要对 TDM 作为一种提高治疗效果的工具进行标准化研究，特别是随着创新的药物浓度感应和 PK-PD 建模技术的出现。提供 TDM 的不同中心生成的数据应开放获取并汇总，以丰富认识并优化应用。
