Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville campus), Parkville, Victoria, Australia.
UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.
Int J Antimicrob Agents. 2020 Jan;55(1):105833. doi: 10.1016/j.ijantimicag.2019.10.014. Epub 2019 Nov 12.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a major global public health challenge. This study aimed to systematically review the evidence on treatment outcomes (mortality, clinical and microbiological response) following antibiotic therapy administered for CRKP infections.
Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts databases were searched from inception to 26 December 2018. Data were analysed via meta-analysis techniques using random-effects (DerSimonian and Laird) modelling.
Fifty-four observational studies involving 3195 CRKP-infected patients who received antibiotic treatment were included. The pooled mortality, clinical and microbiological response rates were 37.2% (95% confidence interval [CI] 33.1-41.4%), 69.0% (95% CI 60.1-78.2%) and 63.7% (95% CI 53.7-74.1%), respectively. Compared with combination therapy, monotherapy was associated with a higher likelihood of mortality (odds ratio [OR] 1.45, 95% CI 1.18-1.78%), but there were no statistically significant differences in the likelihood of achieving clinical and microbiological responses. There were no statistically significant differences in the pooled likelihood of mortality, clinical or microbiological responses between two-drug and three-or-more-drug combination therapies or combination-containing and combination-sparing regimens of polymyxins, tigecycline, aminoglycosides and carbapenems. Moreover, clinical outcomes did not significantly differ among the various monotherapies.
These data highlight the need for systematic studies and well-designed randomised clinical trials to identify and evaluate the most appropriate antibiotic therapies for CRKP infections towards informing clinical decision-making. Furthermore, continuous surveillance of antimicrobial susceptibility patterns at local, regional, and national/international levels are important to support empirically-based therapy until susceptibility results for the isolate from the patient are available.
耐碳青霉烯类肺炎克雷伯菌（CRKP）感染是一个重大的全球公共卫生挑战。本研究旨在系统综述抗生素治疗耐碳青霉烯类肺炎克雷伯菌感染的治疗结局（死亡率、临床和微生物学反应）的证据。
从建库至 2018 年 12 月 26 日，检索 Medline、EMBASE、Cochrane 中央对照试验注册库和国际药学文摘数据库，采用随机效应（DerSimonian 和 Laird）模型进行荟萃分析。
共纳入 54 项包含 3195 例接受抗生素治疗的耐碳青霉烯类肺炎克雷伯菌感染患者的观察性研究。汇总的死亡率、临床和微生物学反应率分别为 37.2%（95%置信区间 [CI] 33.1-41.4%）、69.0%（95% CI 60.1-78.2%）和 63.7%（95% CI 53.7-74.1%）。与联合治疗相比，单药治疗与更高的死亡率相关（比值比 [OR] 1.45，95% CI 1.18-1.78%），但在临床和微生物学反应的可能性方面无统计学差异。两种药物和三种或更多种药物联合治疗或包含联合用药和不包含联合用药的多黏菌素、替加环素、氨基糖苷类和碳青霉烯类方案之间，死亡率、临床或微生物学反应的汇总可能性无统计学差异。此外，各种单药治疗的临床结局也无显著差异。
这些数据强调需要系统研究和精心设计的随机临床试验，以确定和评估最适合耐碳青霉烯类肺炎克雷伯菌感染的抗生素治疗方法，从而为临床决策提供信息。此外，在地方、区域和国家/国际各级，持续监测抗菌药物敏感性模式对于在获得患者分离株的药敏结果之前，支持基于经验的治疗非常重要。
