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碳青霉烯类药物敏感性降低的肠杆菌科成员的替加环素和多黏菌素 B 的基因型特征和体外活性。

Genotypic characterization and in vitro activities of tigecycline and polymyxin B for members of the Enterobacteriaceae with decreased susceptibility to carbapenems.

机构信息

Graduate School in Pharmaceutical Science, Osaka University, Japan.

Second Affiliated Hospital of Zhejiang University, 88 Jiefang Rd, Hangzhou 310009, PR China.

出版信息

J Med Microbiol. 2011 Dec;60(Pt 12):1813-1819. doi: 10.1099/jmm.0.025668-0. Epub 2011 Aug 11.

DOI:10.1099/jmm.0.025668-0
PMID:21835972
Abstract

Carbapenem resistance in members of the Enterobacteriaceae is increasing. To evaluate the effects of tigecycline and polymyxin B against carbapenem-non-susceptible pathogens, 89 representative clinical carbapenem-non-susceptible Enterobacteriaceae isolates were recovered from seven hospitals from four cities in China during 2006-2009: 30 Serratia marcescens, 35 Klebsiella pneumoniae, seven Enterobacter cloacae, six Enterobacter aerogenes, five Escherichia coli, four Citrobacter freundii and two Klebsiella oxytoca isolates. Twenty-eight S. marcescens isolates were indistinguishable. The 35 K. pneumoniae isolates belonged to 12 clonal strains. Among the 89 Enterobacteriaceae isolates, 82 produced KPC-2, seven produced IMP (three produced KPC-2 simultaneously), three did not produce any carbapenemases and nine were deficient in porins. Polymyxin B was much more active than tigecycline against carbapenem-non-susceptible Enterobacteriaceae. The MIC(50) and MIC(90) of imipenem, meropenem, ertapenem, polymyxin B and tigecycline were 8 and 32 µg ml(-1), 8 and 32 µg ml(-1), 16 and 128 µg ml(-1), 0.5 and 16 µg ml(-1), and 4 and 16 µg ml(-1), respectively. Rates of susceptibility to imipenem, meropenem, ertapenem and polymyxin B were 30.0%, 27.5%, 2.5% and 89.2% by CLSI criteria. The rate of susceptibility to tigecycline was 40% and 17.5% by Food and Drug Administration (MIC ≤2 µg ml(-1)) and European Committee on Antimicrobial Susceptibility Testing (MIC ≤1 µg ml(-1)) criteria, respectively. KPC-2- or IMP-producing E. coli transconjugants exhibited reduced susceptibility to carbapenems but were susceptible to polymyxin B and tigecycline with an MIC range of 0.5-2 µg ml(-1), 0.25-2 µg ml(-1), 0.5-4 µg ml(-1), 0.5 µg ml(-1) and 0.5-1 µg ml(-1). In conclusion, carbapenem resistance in Enterobacteriaceae is mainly due to production of KPC-2, and polymyxin B is active for the carbapenem-resistant Enterobacteriaceae.

摘要

肠杆菌科的碳青霉烯类耐药性正在增加。为了评估替加环素和多黏菌素 B 对碳青霉烯类不敏感病原体的作用,从中国四个城市的七家医院收集了 89 株具有代表性的临床碳青霉烯类不敏感肠杆菌科分离株,包括 30 株粘质沙雷氏菌、35 株肺炎克雷伯菌、7 株阴沟肠杆菌、6 株产气肠杆菌、5 株大肠埃希菌、4 株弗氏柠檬酸杆菌和 2 株产酸克雷伯菌。28 株粘质沙雷氏菌分离株无法区分。35 株肺炎克雷伯菌分离株属于 12 个克隆株。在 89 株肠杆菌科分离株中,82 株产生 KPC-2,7 株产生 IMP(3 株同时产生 KPC-2),3 株不产生任何碳青霉烯酶,9 株缺乏孔蛋白。多黏菌素 B 对碳青霉烯类不敏感的肠杆菌科具有比替加环素更高的活性。亚胺培南、美罗培南、厄他培南、多黏菌素 B 和替加环素的 MIC(50)和 MIC(90)分别为 8 和 32μg/ml、8 和 32μg/ml、16 和 128μg/ml、0.5 和 16μg/ml、4 和 16μg/ml。按 CLSI 标准,亚胺培南、美罗培南、厄他培南和多黏菌素 B 的敏感性率分别为 30.0%、27.5%、2.5%和 89.2%。按美国食品和药物管理局(MIC≤2μg/ml)和欧洲抗菌药物敏感性试验委员会(MIC≤1μg/ml)标准,替加环素的敏感性率分别为 40%和 17.5%。产 KPC-2 或 IMP 的大肠埃希菌转座子对碳青霉烯类的敏感性降低,但对多黏菌素 B 和替加环素敏感,MIC 范围分别为 0.5-2μg/ml、0.25-2μg/ml、0.5-4μg/ml、0.5μg/ml 和 0.5-1μg/ml。总之,肠杆菌科的碳青霉烯类耐药性主要是由于 KPC-2 的产生,多黏菌素 B 对碳青霉烯类耐药的肠杆菌科具有活性。

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