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外排泵抑制剂在降低伊朗一家烧伤医院铜绿假单胞菌抗生素交叉耐药性中的作用

Role of efflux pump inhibitor in decreasing antibiotic cross-resistance of Pseudomonas aeruginosa in a burn hospital in Iran.

作者信息

Talebi-Taher Mahshid, Majidpour َAli, Gholami Abbas, Rasouli-Kouhi Samira, Adabi Maryam

机构信息

Rasool-Akram hospital, Iran University of Medical Sciences, Tehran, Iran.

出版信息

J Infect Dev Ctries. 2016 Jun 30;10(6):600-4. doi: 10.3855/jidc.7619.

Abstract

INTRODUCTION

Multidrug resistance in Pseudomonas aeruginosa may be due to efflux pump overexpression. This study phenotypically examined the role of efflux pump inhibitors in decreasing antibiotic cross-resistance between beta-lactams, fluoroquinolones, and aminoglycosides in P. aeruginosa isolates from burn patients in Iran.

METHODOLOGY

A total of 91 phenotypically and genotypically confirmed P. aeruginosa samples were studied. Multidrug cross-resistance was determined using the disk diffusion method and minimum inhibitory concentration (MIC) test. The contribution of efflux pumps was determined by investigating MIC reduction assay to markers of beta-lactams, fluoroquinolones, and aminoglycosides in the absence and presence of an efflux pump inhibitor. All the isolates were also tested by polymerase chain reaction for the presence of mexA, mexC, and mexE efflux genes.

RESULTS

Of the isolates, 81 (89%) and 83 (91.2%) were multidrug resistant according to the disk diffusion and MIC method, respectively. Cross-resistance was observed in 67 (73.6%) and 68 (74.7%) of isolates according to the disk diffusion and MIC method, respectively. In the presence of the efflux pump inhibitor, twofold or higher MIC reduction to imipenem, cefepime, ciprofloxacin, and gentamicin was observed in 59, 65, 55, and 60 isolates, respectively. Except for two isolates that were negative for mexC, all isolates were positive for mexA, mexC, and mexE genes simultaneously.

CONCLUSION

Efflux pumps could cause different levels of resistance based on their expression in clinical isolates. Early detection of different efflux pumps in P. aeruginosa could allow the use of other antibiotics and efflux pump inhibitors in combination with antibiotic therapy.

摘要

引言

铜绿假单胞菌中的多重耐药性可能归因于外排泵的过度表达。本研究从表型上考察了外排泵抑制剂在降低伊朗烧伤患者分离出的铜绿假单胞菌中β-内酰胺类、氟喹诺酮类和氨基糖苷类抗生素之间交叉耐药性方面的作用。

方法

共研究了91份经表型和基因型确认的铜绿假单胞菌样本。采用纸片扩散法和最低抑菌浓度(MIC)试验确定多重耐药交叉性。通过研究在有无外排泵抑制剂的情况下,MIC降低试验对β-内酰胺类、氟喹诺酮类和氨基糖苷类标志物的影响来确定外排泵的作用。所有分离株还通过聚合酶链反应检测mexA、mexC和mexE外排基因的存在情况。

结果

根据纸片扩散法和MIC法,分别有81株(89%)和83株(91.2%)分离株对多种药物耐药。根据纸片扩散法和MIC法,分别有67株(73.6%)和68株(74.7%)分离株存在交叉耐药。在外排泵抑制剂存在的情况下,分别在59株、65株、55株和60株分离株中观察到对亚胺培南、头孢吡肟、环丙沙星和庆大霉素的MIC降低两倍或更高。除两株mexC呈阴性的分离株外,所有分离株的mexA、mexC和mexE基因均同时呈阳性。

结论

外排泵可根据其在临床分离株中的表达导致不同程度的耐药性。早期检测铜绿假单胞菌中的不同外排泵可使其他抗生素和外排泵抑制剂与抗生素治疗联合使用。

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