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研究体外槲皮素-美罗培南联合用药对产碳青霉烯酶肺炎克雷伯菌的疗效。

Investigation of in vitro efficacy of quercetin-meropenem combination in carbapenemase-producing Klebsiella pneumoniae isolates.

机构信息

Sakarya University, Faculty of Medicine, Department of Medical Biology, Sakarya, Turkey.

Sakarya University, Faculty of Science and Art, Department of Chemistry, Sakarya, Turkey.

出版信息

J Infect Dev Ctries. 2023 Sep 30;17(9):1325-1329. doi: 10.3855/jidc.17635.

Abstract

INTRODUCTION

In recent years, the rapid spread of carbapenem-resistant K. pneumoniae, their higher mortality rates, and limited treatment alternatives cause difficulties in the treatment of these infections. New treatment alternatives are needed to cope with resistant strains. In recent years, natural products such as Quercetin have started to be preferred in combination studies due to their antimicrobial effects and low side-effect profiles. The aim of this study was to investigate the in vitro efficacy of the combination of Quercetin and Meropenem on carbapenemase-producing (blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP), carbapenem-resistant K.pneumoniae isolates using the checkerboard method.

METHODOLOGY

Thirty Carbapenem-resistant K.pneumoniae strains in the culture collection of our laboratory were included in our study. Carbapenemase genes were determined using the Xpert® Carba-R (Cepheid, USA). Synergism with meropenem was assessed by checkerboard analysis, followed by FIC index, and combination index calculation.

RESULTS

Twenty (66.6%) strains had OXA-48, 6 (20%) NDM, 1 (3.3%) KPC, 1 (3.3%) OXA-48+NDM genes, and 2 strains (6.6%) gene could not be detected. In the Quercetin and Meropenem combination study, synergy was found in 24 (80%) of the strains; an additive effect was found in 5 (16.6%) and an antagonist effect in 1 (3.3%). In 19 (63.3%) of the strains, meropenem MIC values were below the sensitive limit (MIC ≤ 2 μg/mL).

CONCLUSIONS

Although the combination of quercetin and meropenem has a high synergistic effect in carbapenem-resistant K. pneumoniae isolates, it seems that the carbapenemase species affects this situation. however, more work is needed on this subject.

摘要

简介

近年来,碳青霉烯类耐药肺炎克雷伯菌的快速传播、较高的死亡率以及有限的治疗选择给这些感染的治疗带来了困难。需要新的治疗选择来应对耐药菌株。近年来,由于具有抗菌作用和低副作用特征,槲皮素等天然产物开始在联合研究中受到青睐。本研究旨在通过棋盘法研究槲皮素与美罗培南联合应用对产碳青霉烯酶(blaKPC、blaNDM、blaVIM、blaOXA-48 和 blaIMP)、碳青霉烯类耐药肺炎克雷伯菌的体外疗效。

方法

我们的实验室培养物库中包括 30 株碳青霉烯类耐药肺炎克雷伯菌。使用 Xpert® Carba-R(Cepheid,美国)确定碳青霉烯酶基因。通过棋盘分析评估与美罗培南的协同作用,然后计算 FIC 指数和组合指数。

结果

20 株(66.6%)菌株具有 OXA-48、6 株(20%)具有 NDM、1 株(3.3%)具有 KPC、1 株(3.3%)具有 OXA-48+NDM 基因,2 株(6.6%)基因无法检测到。在槲皮素和美罗培南联合研究中,24 株(80%)菌株表现出协同作用;5 株(16.6%)菌株表现出相加作用,1 株(3.3%)菌株表现出拮抗作用。在 19 株(63.3%)菌株中,美罗培南 MIC 值低于敏感限(MIC≤2μg/mL)。

结论

虽然在碳青霉烯类耐药肺炎克雷伯菌分离株中,槲皮素和美罗培南联合应用具有很高的协同作用,但碳青霉烯酶种类似乎影响了这种情况。然而,需要在这一主题上开展更多的工作。

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