Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Laboratorio de Microbiología, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
J Med Microbiol. 2012 Sep;61(Pt 9):1270-1279. doi: 10.1099/jmm.0.045799-0. Epub 2012 Jun 14.
The main goal of this work was to identify the mechanisms responsible for carbapenem resistance in 61 Chilean clinical isolates of Enterobacteriaceae (Enterobacter spp., Serratia marcescens, Morganella morganii, Escherichia coli and Klebsiella pneumoniae) with reduced susceptibility to at least one carbapenem (ertapenem, imipenem or meropenem). All of the isolates were analysed for the presence of carbapenemases, extended spectrum β-lactamases (ESBLs), AmpC enzymes and outer-membrane proteins. None of the isolates exhibited carbapenemase activity nor did they have any of the carbapenemase genes that were screened for. Most of the 61 strains produced at least one ESBL and/or one AmpC enzyme and either lost their porins or had altered porins according to sequence analysis. The distribution of ESBLs and AmpC enzymes was different among the species studied. Resistance in K. pneumoniae and E. coli isolates was associated with ESBLs; in M. morganii isolates, resistance was attributed to overexpression of an AmpC enzyme; and in Enterobacter spp. isolates, resistance was associated with both types of enzymes. In K. pneumoniae isolates, porin integrity was more a determinant of carbapenem resistance than the presence of ESBLs, whereas in isolates of Enterobacter spp., M. morganii and S. marcescens, the presence of an overexpressed AmpC enzyme was associated with higher imipenem and meropenem MIC values. Therefore, carbapenem resistance in Chilean isolates is not due to true carbapenemases but rather to a combination of porin loss/alteration and β-lactamase activity. The fact that carbapenemases were not detected in this study is unique, given that many countries in the region have already reported the presence of these enzymes.
本研究的主要目的是确定 61 株智利临床分离的肠杆菌科（肠杆菌属、黏质沙雷氏菌、摩氏摩根菌、大肠埃希菌和肺炎克雷伯菌）对至少一种碳青霉烯类药物（厄他培南、亚胺培南或美罗培南）呈现低水平耐药的机制。对所有分离株进行了碳青霉烯酶、超广谱β-内酰胺酶（ESBLs）、AmpC 酶和外膜蛋白的检测。没有分离株显示碳青霉烯酶活性，也没有筛选出任何碳青霉烯酶基因。61 株菌中大多数至少产生了一种 ESBL 和/或一种 AmpC 酶，并且根据序列分析，它们的孔蛋白要么丢失，要么发生了改变。在所研究的种属中，ESBLs 和 AmpC 酶的分布不同。肺炎克雷伯菌和大肠埃希菌分离株的耐药性与 ESBLs 有关；摩根摩根菌分离株的耐药性归因于 AmpC 酶的过度表达；肠杆菌属分离株的耐药性与这两种酶有关。在肺炎克雷伯菌分离株中，孔蛋白完整性比 ESBLs 的存在更能决定碳青霉烯类药物的耐药性，而在肠杆菌属、摩根摩根菌和黏质沙雷氏菌分离株中，过表达的 AmpC 酶的存在与更高的亚胺培南和美罗培南 MIC 值有关。因此，智利分离株的碳青霉烯类耐药性不是由于真正的碳青霉烯酶，而是由于孔蛋白缺失/改变和β-内酰胺酶活性的组合。在本研究中未检测到碳青霉烯酶这一事实是独特的，因为该地区的许多国家已经报告了这些酶的存在。
