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从伊朗伊斯法罕医院分离出的耐碳青霉烯肺炎克雷伯菌(CRKP)的频率测定及黏菌素与美罗培南对其协同作用的评估。

Frequency Determination of Carbapenem-Resistant Klebsiella Pneumoniae (CRKP) Isolated from hospitals in Isfahan of Iran and Evaluation of Synergistic Effect of Colistin and Meropenem on them.

作者信息

Gheitani Leila, Fazeli Hossein, Moghim Sharareh, Nasr Isfahani Bahram

机构信息

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

出版信息

Cell Mol Biol (Noisy-le-grand). 2018 Jan 31;64(1):70-74. doi: 10.14715/cmb/2018.64.1.13.

DOI:10.14715/cmb/2018.64.1.13
PMID:29412797
Abstract

Overuse and misuse of Carbapenems among Klebsiella pneumoniae isolates have caused Carbapenem-Resistant Klebsiella Pneumonia (CRKP) during recent years. Colistin is one of the last available options, and there are increasing concerns about the dosage and resistance to this agent in long-term monotherapies. This study was designed to identification of carbapenemase producing isolates of K. pneumoniae via phenotypic and genotypic methods as well as evaluation of colistin-meropenem combination therapy potential. This study was carried out in Isfahan, of Iran on 100 samples from Alzahra and Khorshid hospitals in 2017. The Modified Hodge Test (MHT) was used to investigate the carbapenemase presence. The minimum inhibitory concentration (MIC) and the Fractional Inhibitory Concentration (FIC) were determined using broth macrodilution and checkerboard assays (respectively) for both meropenem and colistin. The bla-KPC gene was studied by polymerase chain reaction (PCR).The highest and the lowest rate of resistance were observed for piperacillin (84%) and ertapenem (50%) respectively. 68 isolates by MHT were CRKP, but None of them were positive for bla-KPC gene. 21 isolates from CRKP cases were high resistant to used antimicrobial agents in the study that both MIC and FIC results showed significant synergy for this antibiotics in checkerboard test (p-value < 0.05). 21 resistant isolates from CRKP cases showed statistically significant synergy potential for meropenem and colistin. The meropenem-colistin combination therapy can be applied as a suitable antibiotic synergy but it requires further investigation in clinical assay. Regarding to our findings, Probably other mechanisms of resistance to Carbapenems ,except bla-kpc genes are involved.

摘要

近年来,肺炎克雷伯菌分离株中碳青霉烯类药物的过度使用和滥用导致了耐碳青霉烯类肺炎克雷伯菌(CRKP)的出现。黏菌素是最后可用的选择之一,人们越来越担心长期单一疗法中该药物的剂量和耐药性问题。本研究旨在通过表型和基因型方法鉴定产碳青霉烯酶的肺炎克雷伯菌分离株,并评估黏菌素-美罗培南联合治疗的潜力。2017年,本研究在伊朗伊斯法罕对来自阿尔扎赫拉医院和霍希德医院的100份样本进行。采用改良 Hodge 试验(MHT)检测碳青霉烯酶的存在。分别使用肉汤稀释法和棋盘稀释法测定美罗培南和黏菌素的最低抑菌浓度(MIC)和分数抑菌浓度(FIC)。通过聚合酶链反应(PCR)研究bla-KPC基因。哌拉西林和厄他培南的耐药率分别为最高(84%)和最低(50%)。通过MHT检测,68株分离株为CRKP,但均未检测出bla-KPC基因阳性。本研究中,21株CRKP病例分离株对所用抗菌药物高度耐药,MIC和FIC结果均显示在棋盘试验中这两种抗生素具有显著协同作用(p值<0.05)。21株CRKP病例耐药分离株对美罗培南和黏菌素显示出具有统计学意义的协同潜力。美罗培南-黏菌素联合治疗可作为一种合适的抗生素联合方案,但需要在临床试验中进一步研究。根据我们的研究结果,除bla-kpc基因外,可能还涉及其他耐碳青霉烯类药物的机制。

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