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探索氟喹诺酮耐药机制以及羰基氰3-氯苯腙(CCCP)在……中的作用

Exploring fluoroquinolone resistance mechanisms and the effects of carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in .

作者信息

Nazari Mohsen, Alikhani Mohammad Sina, Hemmati Jaber, Ahmadi Amjad, Hashemi Seyyed Hamid, Alikhani Mohammad Yousef

机构信息

Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Front Med (Lausanne). 2025 May 9;12. doi: 10.3389/fmed.2025.1527662. eCollection 2025.

DOI:10.3389/fmed.2025.1527662
PMID:40417689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12098036/
Abstract

OBJECTIVES

This study aims to investigate the prevalence and mechanisms of fluoroquinolone resistance in strains isolated from hospitals in Hamadan, west of Iran. It investigates the role of specific resistance genes and mutations in contributing to this resistance. In addition, the effects of carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on the susceptibility of to fluoroquinolones will be evaluated to identify potential strategies to combat this growing problem.

METHODS

A total of 102 isolates were collected from various clinical specimens between February and August 2023. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method according to CLSI guidelines, focusing on eight antibiotics, including ciprofloxacin and levofloxacin. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) evaluations were also performed for these fluoroquinolones. The presence of plasmid-dependent fluoroquinolone resistance (PMQR) genes and mutations in the gyrA and parC genes were assessed by PCR. The effect of CCCP on antibiotic susceptibility and expression of efflux pump encoding gene was evaluated by real-time PCR.

RESULTS

The study revealed alarmingly high resistance rates among the 102 isolates, with 97% resistant to imipenem, 96% to gentamicin, 92% to ciprofloxacin, and 86% to levofloxacin. Of the isolates, 87 were classified as multidrug resistant (MDR). Several resistance genes were identified, including (77.45%), (73.52%), and (72.54%). Mutations in the and genes were detected in several isolates, contributing to the observed resistance. In addition, treatment with CCCP resulted in a significant reduction in MICs for both ciprofloxacin and levofloxacin, highlighting its potential role in mitigating resistance.

CONCLUSION

The findings underscore the urgent need for improved surveillance and treatment strategies due to the high prevalence of fluoroquinolone resistance. While CCCP demonstrated potential in restoring antibiotic susceptibility, further studies are needed to assess its clinical applicability and potential toxicity. Additionally, the study is limited by its focus on a single geographic region, and further investigations across broader populations are necessary to generalize these findings.

摘要

目的

本研究旨在调查从伊朗西部哈马丹医院分离出的菌株中氟喹诺酮耐药性的流行情况及机制。研究特定耐药基因和突变在导致这种耐药性方面的作用。此外,将评估羰基氰3-氯苯腙(CCCP)对菌株对氟喹诺酮敏感性的影响,以确定应对这一日益严重问题的潜在策略。

方法

2023年2月至8月期间,从各种临床标本中总共收集了102株菌株。根据CLSI指南,使用 Kirby-Bauer 纸片扩散法进行药敏试验,重点关注包括环丙沙星和左氧氟沙星在内的八种抗生素。还对这些氟喹诺酮进行了最低抑菌浓度(MIC)和最低杀菌浓度(MBC)评估。通过PCR评估质粒介导的氟喹诺酮耐药性(PMQR)基因以及gyrA和parC基因中的突变。通过实时PCR评估CCCP对抗生素敏感性和外排泵编码基因表达的影响。

结果

研究显示,在这102株菌株中,耐药率高得惊人,对亚胺培南耐药的占97%,对庆大霉素耐药的占96%,对环丙沙星耐药的占92%,对左氧氟沙星耐药的占86%。在这些分离株中,87株被归类为多重耐药(MDR)。鉴定出了几种耐药基因,包括qnr(77.45%)、aac(6’)-Ib-cr(73.52%)和oqxA(72.54%)。在一些分离株中检测到gyrA和parC基因的突变,这导致了观察到的耐药性。此外,用CCCP处理导致环丙沙星和左氧氟沙星的MIC显著降低,突出了其在减轻耐药性方面的潜在作用。

结论

研究结果强调,鉴于氟喹诺酮耐药性的高流行率,迫切需要改进监测和治疗策略。虽然CCCP在恢复抗生素敏感性方面显示出潜力,但需要进一步研究以评估其临床适用性和潜在毒性。此外,该研究受限于其仅关注单一地理区域,有必要在更广泛的人群中进行进一步调查,以推广这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f790/12098036/f0442a041946/fmed-12-1527662-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f790/12098036/e3bfdec9785a/fmed-12-1527662-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f790/12098036/f17e55559fce/fmed-12-1527662-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f790/12098036/f0442a041946/fmed-12-1527662-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f790/12098036/e3bfdec9785a/fmed-12-1527662-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f790/12098036/f17e55559fce/fmed-12-1527662-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f790/12098036/f0442a041946/fmed-12-1527662-g003.jpg

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