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将丁香酚与头孢噻肟和环丙沙星联合使用以对抗产 ESBL 的喹诺酮类耐药肠杆菌科病原菌。

The use of eugenol in combination with cefotaxime and ciprofloxacin to combat ESBL-producing quinolone-resistant pathogenic Enterobacteriaceae.

机构信息

Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Kolkata, India.

出版信息

J Appl Microbiol. 2020 Dec;129(6):1566-1576. doi: 10.1111/jam.14737. Epub 2020 Jul 16.

DOI:10.1111/jam.14737
PMID:32502298
Abstract

AIM

Emergence of extended-spectrum beta-lactamase (ESBL) producing with quinolone-resistant (QR) pathogenic Enterobacteriaceae augmented the need to establish therapeutic options against them. Present study aimed towards determination of synergistic combination of eugenol (EG) with cefotaxime (CTX) and ciprofloxacin (CIP) to combat against this resistance and potentiation of antibacterial drugs by EG against these bacteria.

METHODS AND RESULTS

Synergistic interaction between EG and CTX/CIP (FICI: 0·08-0·5) were observed among ESBL-QR bacteria using checkerboard assay. Approximately, 2- to 1024-fold minimum inhibitory concentration value reduction and 17- to 165 030-fold dose reduction index strongly suggested synergistic interaction between EG and antibiotics. Cell viability assay showed reduction in log CFU per ml from 16·6 to 3·1 at synergistic concentration. Scanning electron microscopy further proved disruptive effect of EG on cell architecture. Eugenol and/or its combination also altered genes' expressions that imparted antibiotic resistance by ~1·6 to ~1226 folds.

CONCLUSIONS

Reduced doses of antibiotics, bacterial morphological alterations, efflux pump down regulation, porin over expression and beta-lactamase gene inhibition of ESBL-QR bacteria by EG alone or in combination with CTX/CIP might have reversed antibiotic resistance profile of ESBL-QR bacteria.

SIGNIFICANCE AND IMPACT OF THE STUDY

This study provided a molecular insight into action of EG and/with CTX and CIP, which might have potentiated antibiotic's activity against ESBL-QR bacteria.

摘要

目的

产生具有喹诺酮耐药性(QR)的扩展谱β-内酰胺酶(ESBL)的肠杆菌科病原体的出现增加了对其建立治疗选择的需求。本研究旨在确定丁香酚(EG)与头孢噻肟(CTX)和环丙沙星(CIP)的协同组合,以对抗这种耐药性,并增强 EG 对这些细菌的抗菌药物作用。

方法和结果

使用棋盘试验观察到 ESBL-QR 细菌中 EG 与 CTX/CIP 之间的协同相互作用(FICI:0.08-0.5)。最低抑菌浓度值降低约 2-1024 倍,剂量降低指数 17-165030 倍,强烈表明 EG 与抗生素之间存在协同相互作用。细胞活力测定显示协同浓度下每毫升对数 CFU 减少从 16.6 到 3.1。扫描电子显微镜进一步证明了 EG 对细胞结构的破坏作用。丁香酚和/或其组合还改变了赋予抗生素耐药性的基因表达,使其增加了 1.6 至 1226 倍。

结论

EG 单独或与 CTX/CIP 联合使用可降低抗生素剂量、改变细菌形态、下调外排泵、过度表达孔蛋白和抑制 ESBL-QR 细菌的β-内酰胺酶基因,从而逆转 ESBL-QR 细菌的抗生素耐药谱。

意义和影响

这项研究提供了 EG 与 CTX 和 CIP 作用的分子见解,这可能增强了抗生素对 ESBL-QR 细菌的活性。

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