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首页> 外文期刊>Journal of Clinical Microbiology >Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae
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Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

机译：表型的可预测性与大肠埃希菌和肺炎克雷伯菌的常见β-内酰胺抗性机制相关

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The minimal concentration of antibiotic required to inhibit the growth of different isolates of a given species with no acquired resistance mechanisms has a normal distribution. We have previously shown that the presence or absence of transmissible antibiotic resistance genes has excellent predictive power for phenotype. In this study, we analyzed the distribution of six β-lactam antibiotic susceptibility phenotypes associated with commonly acquired resistance genes in Enterobacteriaceae in Sydney, Australia. Escherichia coli (n = 200) and Klebsiella pneumoniae (n = 178) clinical isolates, with relevant transmissible resistance genes (blaTEM, n = 33; plasmid AmpC, n = 69; extended-spectrum β-lactamase [ESBL], n = 116; and carbapenemase, n = 100), were characterized. A group of 60 isolates with no phenotypic resistance to any antibiotics tested and carrying none of the important β-lactamase genes served as comparators. The MICs for all drug-bacterium combinations had a normal distribution, varying only in the presence of additional genes relevant to the phenotype or, for ertapenem resistance in K. pneumoniae, with a loss or change in the outer membrane porin protein OmpK36. We demonstrated mutations in ompK36 or absence of OmpK36 in all isolates in which reduced susceptibility to ertapenem (MIC, >1 mg/liter) was evident. Ertapenem nonsusceptibility in K. pneumoniae was most common in the context of an OmpK36 variant with an ESBL or AmpC gene. Surveillance strategies to define appropriate antimicrobial therapies should include genotype-phenotype relationships for all major transmissible resistance genes and the characterization of mutations in relevant porins in organisms, like K. pneumoniae.
机译：在没有获得性耐药机制的情况下，抑制给定物种的不同分离株生长所需的最低抗生素浓度具有正态分布。先前我们已经表明，是否存在可传播的抗生素抗性基因对表型具有出色的预测能力。在这项研究中，我们分析了澳大利亚悉尼肠杆菌科中与常见耐药基因相关的六种β-内酰胺抗生素敏感性表型的分布。大肠杆菌（ n = 200）和肺炎克雷伯菌（ n = 178）临床分离株，具有相关的可传播抗性基因（ bla TEM ， n = 33;质粒AmpC， n = 69;超广谱β-内酰胺酶[ESBL]， n = 116 ;碳青霉烯酶 n = 100）。一组60个对测试的抗生素没有表型抗性且不携带任何重要的β-内酰胺酶基因的分离株作为对照。所有药物-细菌组合的MIC均具有正态分布，仅在存在与该表型相关的其他基因或肺炎克雷伯菌中对厄他培南的耐药性时，外膜孔蛋白OmpK36丢失或发生变化。我们证明了所有细菌中 ompK36 的突变或OmpK36的缺失，其中对厄他培南的敏感性降低了（MIC，> 1 mg / L）。在带有ESBL或AmpC基因的OmpK36变异体中，肺炎克雷伯菌中厄他培南的不敏感性最为常见。定义适当的抗菌疗法的监测策略应包括所有主要可传播抗性基因的基因型与表型关系，以及诸如肺炎克雷伯氏菌等生物体相关孔蛋白突变的特征。

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