PDF(Pubmed)
Abstract：
To perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the clinical efficacy for treating Gram-negative infections in critical patients, and of identifying predictive factors of failure in attaining aggressive PK/PD targets.
Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs. conservative PK/PD targets on clinical efficacy of beta-lactams. Independent predictive factors of failure in attaining aggressive PK/PD targets were also assessed. Aggressive PK/PD target was considered a100%fT>4xMIC, and clinical cure rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with inverse variance method.
A total of 20,364 articles were screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 aggressive vs. 2640 conservative PK/PD target). Attaining aggressive PK/PD target was significantly associated with higher clinical cure rate (OR 1.69; 95% CI 1.15-2.49) and lower risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01-0.29). Male gender, body mass index > 30 kg/m2, augmented renal clearance and MIC above the clinical breakpoint emerged as significant independent predictors of failure in attaining aggressive PK/PD targets, whereas prolonged/continuous infusion administration of beta-lactams resulted as protective factor. The risk of bias was moderate in 19 studies and severe in the other 2.
Attaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.
Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs. conservative PK/PD targets on clinical efficacy of beta-lactams. Independent predictive factors of failure in attaining aggressive PK/PD targets were also assessed. Aggressive PK/PD target was considered a100%fT>4xMIC, and clinical cure rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with inverse variance method.
A total of 20,364 articles were screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 aggressive vs. 2640 conservative PK/PD target). Attaining aggressive PK/PD target was significantly associated with higher clinical cure rate (OR 1.69; 95% CI 1.15-2.49) and lower risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01-0.29). Male gender, body mass index > 30 kg/m2, augmented renal clearance and MIC above the clinical breakpoint emerged as significant independent predictors of failure in attaining aggressive PK/PD targets, whereas prolonged/continuous infusion administration of beta-lactams resulted as protective factor. The risk of bias was moderate in 19 studies and severe in the other 2.
Attaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.
摘要：
背景：使用荟萃分析进行系统评价，其目的是评估获得侵略性与保守的β-内酰胺类PK/PD目标是治疗重症患者革兰氏阴性感染的临床疗效，以及确定在实现积极的PK/PD目标方面失败的预测因素。
方法：两位作者从成立到2023年12月23日独立搜索了PubMed-MEDLINE和Scopus数据库，以检索比较获得侵略性与侵略性的影响的研究。保守的PK/PD目标对β-内酰胺类药物临床疗效的影响。还评估了未能达到积极PK/PD目标的独立预测因素。积极的PK/PD目标被认为是100%fT>4xMIC，选择临床治愈率作为主要结局。荟萃分析是通过汇总从研究中推断的比值比（OR）进行的，这些研究使用具有逆方差方法的随机效应模型对混杂因素进行调整。
结果：共筛选了20,364篇文章，和21项观察性研究纳入荟萃分析(N=4833；2193项积极与2640保守PK/PD目标）。达到积极的PK/PD目标与较高的临床治愈率（OR1.69;95％CI1.15-2.49）和较低的β-内酰胺耐药性发展风险（OR0.06;95％CI0.01-0.29）显着相关。男性,体重指数>30kg/m2，肾脏清除率增加和临床断点以上的MIC作为达到积极的PK/PD目标失败的重要独立预测因子，而延长/连续输注β-内酰胺类药物作为保护因子。在19项研究中，偏倚的风险是中等的，在其他2项研究中是严重的。
结论：获得积极的β-内酰胺类PK/PD目标在危重患者中提供了显著的临床益处。我们的分析可能有助于对在达到积极的PK/PD目标方面失败的高风险患者进行分层。
方法：两位作者从成立到2023年12月23日独立搜索了PubMed-MEDLINE和Scopus数据库，以检索比较获得侵略性与侵略性的影响的研究。保守的PK/PD目标对β-内酰胺类药物临床疗效的影响。还评估了未能达到积极PK/PD目标的独立预测因素。积极的PK/PD目标被认为是100%fT>4xMIC，选择临床治愈率作为主要结局。荟萃分析是通过汇总从研究中推断的比值比（OR）进行的，这些研究使用具有逆方差方法的随机效应模型对混杂因素进行调整。
结果：共筛选了20,364篇文章，和21项观察性研究纳入荟萃分析(N=4833；2193项积极与2640保守PK/PD目标）。达到积极的PK/PD目标与较高的临床治愈率（OR1.69;95％CI1.15-2.49）和较低的β-内酰胺耐药性发展风险（OR0.06;95％CI0.01-0.29）显着相关。男性,体重指数>30kg/m2，肾脏清除率增加和临床断点以上的MIC作为达到积极的PK/PD目标失败的重要独立预测因子，而延长/连续输注β-内酰胺类药物作为保护因子。在19项研究中，偏倚的风险是中等的，在其他2项研究中是严重的。
结论：获得积极的β-内酰胺类PK/PD目标在危重患者中提供了显著的临床益处。我们的分析可能有助于对在达到积极的PK/PD目标方面失败的高风险患者进行分层。
