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多黏菌素负荷剂量联合或不联合美罗培南治疗碳青霉烯类耐药鲍曼不动杆菌的疗效和肾毒性。

The effectiveness and nephrotoxicity of loading dose colistin combined with or without meropenem for the treatment of carbapenem-resistant A. baumannii.

机构信息

Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand, 50200; Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai, Thailand, 50200.

Department of Pharmaceutical Care, School of Pharmacy, Walailak University, Nakhon Si Thammarat, Thailand, 80161.

出版信息

Int J Infect Dis. 2020 Aug;97:391-395. doi: 10.1016/j.ijid.2020.05.100. Epub 2020 Jun 2.

Abstract

INTRODUCTION

Acinetobacter baumannii has emerged as an important nosocomial pathogen worldwide. In Thailand, the incidence and mortality rate of carbapenem-resistant A. baumannii (CRAB) is continuously increasing. This organism is a common pathogen that can cause HAP and VAP. CRAB tends to be susceptible to only colistin, so colistin would be the last line of treatment for CRAB. The recent data from in-vitro studies found that colistin and meropenem combination therapy could exert synergistic effects. However, some in-vivo studies have shown no significant difference in antibacterial effect between colistin monotherapy and colistin plus meropenem. Moreover, the clinical data are recently limited and not clear. Thus, the objective of this study was to compare clinical outcome, microbiological response, mortality rate and nephrotoxicity between loading dose (LD) colistin monotherapy and LD colistin-meropenem for treatment of infection caused by CRAB in Maharaj Nakorn Chiang Mai Hospital.

MATERIALS AND METHODS

This study is a retrospective analytical study. The data were collected from patients who received LD colistin monotherapy or LD colistin plus meropenem combination therapy for treatment of CRAB from 1 January 2013 to 31 August 2017 at Maharaj Nakorn Chiang Mai Hospital. A total of 324 patients met the inclusion criteria. The data were analyzed by descriptive statistics and inferential statistics, and were adjusted for confounding factors by logistic regression analysis.

RESULTS

The adjusted OR of good clinical outcome of patients who received LD colistin plus meropenem was 1.05 times that of patients who received loading dose colistin monotherapy (95%CI 0.62-1.74, p=0.860). Patients who received LD colistin plus meropenem had 0.93 times (adjusted OR) mortality rate at the end of treatment compared to patients who received LD colistin monotherapy (95%CI=0.51-1.71, p=0.935). In addition, microbiological response was defined as eradication of pre-treatment isolated pathogens in post-treatment cultures. Patients who received LD colistin plus meropenem could eradicate pathogens 1.28 times more than LD colistin monotherapy (95% CI=0.74-2.20, p=0.371). Also there was no significant difference in nephrotoxicity (adjusted OR=0.84, 95% CI 0.52-1.36, p=0.492) between LD colistin monotherapy and LD colistin plus meropenem.

CONCLUSION

There were no significant differences in effectiveness and nephrotoxicity of LD colistin monotherapy versus LD colistin plus meropenem for treatment of CRAB infection, so colistin combination therapy was not necessary for the management of infection caused by CRAB.

摘要

简介

鲍曼不动杆菌已成为全球重要的医院获得性病原体。在泰国,耐碳青霉烯鲍曼不动杆菌(CRAB)的发病率和死亡率持续上升。这种病原体是一种常见的致病菌,可引起 HAP 和 VAP。CRAB 往往仅对黏菌素敏感,因此黏菌素是治疗 CRAB 的最后一线药物。最近的体外研究数据发现,黏菌素和美罗培南联合治疗可发挥协同作用。然而,一些体内研究表明,黏菌素单药治疗与黏菌素联合美罗培南治疗在抗菌效果方面无显著差异。此外,临床数据最近较为有限且不明确。因此,本研究的目的是比较负荷剂量(LD)黏菌素单药治疗与 LD 黏菌素-美罗培南联合治疗治疗玛哈沙拉堪差那莱医院 CRAB 感染的临床结局、微生物学反应、死亡率和肾毒性。

材料与方法

这是一项回顾性分析研究。研究数据来自于 2013 年 1 月 1 日至 2017 年 8 月 31 日期间在玛哈沙拉堪差那莱医院接受 LD 黏菌素单药或 LD 黏菌素-美罗培南联合治疗 CRAB 的患者。共有 324 名患者符合纳入标准。数据采用描述性统计和推断性统计进行分析,并通过 logistic 回归分析对混杂因素进行调整。

结果

接受 LD 黏菌素联合美罗培南治疗的患者临床结局良好的调整优势比(OR)为接受 LD 黏菌素单药治疗的患者的 1.05 倍(95%CI 0.62-1.74,p=0.860)。与接受 LD 黏菌素单药治疗的患者相比,接受 LD 黏菌素联合美罗培南治疗的患者在治疗结束时的死亡率降低 0.93 倍(调整 OR)(95%CI=0.51-1.71,p=0.935)。此外,微生物学反应定义为治疗后培养物中清除治疗前分离出的病原体。接受 LD 黏菌素联合美罗培南治疗的患者清除病原体的可能性比 LD 黏菌素单药治疗高 1.28 倍(95%CI=0.74-2.20,p=0.371)。同时,LD 黏菌素单药治疗与 LD 黏菌素联合美罗培南治疗的肾毒性(调整 OR=0.84,95%CI 0.52-1.36,p=0.492)无显著差异。

结论

LD 黏菌素单药治疗与 LD 黏菌素联合美罗培南治疗治疗 CRAB 感染的疗效和肾毒性无显著差异,因此对于 CRAB 引起的感染,黏菌素联合治疗并非必要。

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