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替卡西林他唑巴坦对来自伊朗德黑兰烧伤患者的鲍曼不动杆菌中阿米卡星 MIC 的协同作用。

Synergistic Effect of Tazobactam on Amikacin MIC in Acinetobacter baumannii Isolated from Burn Patients in Tehran, Iran.

机构信息

Paediatric Infections Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Microbiology, Islamic Azad University, North Tehran Branch, Tehran, Iran.

出版信息

Curr Pharm Biotechnol. 2020;21(10):997-1004. doi: 10.2174/1389201021666200220121122.

Abstract

BACKGROUND

Burn is still an important global public health challenge. Wound colonization of antibiotic resistant bacteria such as Acinetobacter baumannii can lead to high morbidity and mortality in burn patients. The aim of this study was to evaluate the inhibitory effect of tazobactam on efflux pump, which can cause aminoglycoside resistant in A. baumannii isolated from burn patients.

METHODS

In this study, 47 aminoglycoside resistant A. baumannii spp. were obtained from burn patients, admitted to the Shahid Motahari Burns Hospital in Tehran, Iran, during June-August 2018. The inhibitory effect of tazobactam against adeB such as efflux pump was evaluated by Minimum Inhibitory Concentration (MIC) determination of amikacin alone and in combination with tazobactam. Fractional Inhibitory Concentration index (FIC) was used to determine the efficacy of tazobactam/ amikacin combination. Further, semi-quantitative Real- Time PCR was performed to quantify the expression rates of the adeB gene before and after addition of tazobactam/amikacin.

RESULTS

The MIC values were significantly reduced when a combined amikacin and tazobactam was utilized. The most common interaction observed was synergistic (78.2%), followed by.additive effects (21.8%), as per FIC results. The adeB mRNA expression levels were found to be downregulated in 60.7% of isolates treated with tazobactam.

CONCLUSION

Tazobactam can have impact on resistance to aminoglycoside by inhibiting efflux pump. Thus, the combination of tazobactam with amikacin can be used as an alternative treatment approach in multidrug resistant A. baumannii infections.

摘要

背景

烧伤仍然是一个重要的全球公共卫生挑战。在烧伤患者中,抗生素耐药菌(如鲍曼不动杆菌)的伤口定植可导致高发病率和死亡率。本研究旨在评估替他唑巴坦对可导致氨基糖苷类耐药的鲍曼不动杆菌外排泵的抑制作用。

方法

本研究中,从 2018 年 6 月至 8 月在伊朗德黑兰沙希德·莫塔哈里烧伤医院住院的烧伤患者中获得了 47 株氨基糖苷类耐药鲍曼不动杆菌。通过单独和联合使用替他唑巴坦测定阿米卡星的最小抑菌浓度(MIC)来评估替他唑巴坦对 adeB 等外排泵的抑制作用。采用部分抑菌浓度指数(FIC)来确定替他唑巴坦/阿米卡星联合用药的疗效。进一步采用半定量实时 PCR 检测替他唑巴坦/阿米卡星联合用药前后 adeB 基因的表达率。

结果

联合使用阿米卡星和替他唑巴坦时,MIC 值显著降低。根据 FIC 结果,观察到最常见的相互作用是协同作用(78.2%),其次是相加作用(21.8%)。用替他唑巴坦处理的 60.7%的分离株 adeB mRNA 表达水平下调。

结论

替他唑巴坦可通过抑制外排泵对氨基糖苷类耐药产生影响。因此,替他唑巴坦与阿米卡星联合使用可作为多重耐药鲍曼不动杆菌感染的替代治疗方法。

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