PDF(Pubmed)
Abstract：
An estimated 70% of critically ill patients receive antibiotics, most frequently beta-lactams. The pharmacokinetic properties of these substances in this patient population are poorly predictable. Therapeutic drug monitoring (TDM) is helpful in making personalized decisions in this field, but its overall impact as a clinical decision-supporting tool is debated. We aimed to evaluate the clinical implications of adjusting beta-lactam dosages based on TDM in the critically ill population by performing a systematic review and meta-analysis of available investigations. Randomized controlled trials and observational studies were retrieved by searching three major databases. The intervention group received TDM-guided beta-lactam treatment, that is, at least one dose reconsideration based on the result of the measurement of drug concentrations, while TDM-unadjusted dosing was employed in the comparison group. The outcomes were evaluated using forest plots with random-effects modeling and subgroup analysis. Eight eligible studies were identified, including 1044 patients in total. TDM-guided beta-lactam treatment was associated with improved clinical cure from infection [odds ratio (OR): 2.22 (95% confidence interval (CI): 1.78-2.76)] and microbiological eradication [OR: 1.72 (CI: 1.05-2.80)], as well as a lower probability of treatment failure [OR: 0.47 (CI: 0.36-0.62)], but the heterogeneity of studies was remarkably high, especially in terms of mortality (70%). The risk of bias was moderate. While the TDM-guided administration of beta-lactams to critically ill patients has a favorable impact, standardized study designs and larger sample sizes are required for developing evidence-based protocols in this field.
摘要：
估计70%的危重病人接受抗生素治疗,最常见的是β-内酰胺。这些物质在该患者群体中的药代动力学特性难以预测。治疗药物监测(TDM)有助于在该领域做出个性化决策，但其作为临床决策支持工具的总体影响仍存在争议.我们旨在通过对现有研究进行系统评价和荟萃分析，评估在危重病人群中基于TDM调整β-内酰胺剂量的临床意义。通过搜索三个主要数据库来检索随机对照试验和观察性研究。干预组接受TDM指导的β-内酰胺治疗,也就是说,基于药物浓度测量结果的至少一次剂量重新考虑，而对照组采用未调整的TDM给药。使用具有随机效应建模和亚组分析的森林地块评估结果。确定了8项符合条件的研究，包括1044名患者。TDM指导的β-内酰胺治疗与改善感染的临床治愈[优势比（OR）：2.22（95％置信区间（CI）：1.78-2.76）]和微生物根除[OR：1.72（CI：1.05-2.80）]相关，以及较低的治疗失败概率[OR：0.47（CI：0.36-0.62）]，但是研究的异质性非常高，尤其是死亡率（70%）。偏倚的风险中等。虽然TDM指导的β-内酰胺类药物对危重病人具有有利的影响，在该领域制定循证方案需要标准化的研究设计和更大的样本量.
