Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae
Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae
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DOI：
10.1128/jcm.02153-15
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发表时间：
2016-05-01
影响因子：
9.4
通讯作者：
Iredell, Jonathan R.
中科院分区：
文献类型：
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作者：
Agyekum, Alex;Fajardo-Lubian, Alicia;Iredell, Jonathan R.
抑制没有获得性耐药机制的给定物种的不同分离株生长所需的抗生素最低浓度呈正态分布。我们之前已经证明，传染性抗生素抗性基因的存在或不存在对表型具有极好的预测能力。在这项研究中，我们分析了澳大利亚悉尼肠杆菌科细菌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。对具有相关传染性耐药基因（bla(TEM)，n = 33；质粒 AmpC，n = 69；超广谱 β-内酰胺酶 [ESBL]，n = 116；和碳青霉烯酶，n = 100）的大肠杆菌 (n = 200) 和肺炎克雷伯菌 (n = 178) 临床分离株进行了表征。一组 60 个对任何测试的抗生素都没有表型耐药性且不携带任何重要 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 均呈正态分布，仅在存在与表型相关的其他基因的情况下变化，或者对于肺炎克雷伯菌的厄他培南耐药性，外膜孔蛋白 OmpK36 丢失或变化。我们证明了所有分离株中的 ompK36 突变或 OmpK36 缺失，其中对厄他培南的敏感性明显降低（MIC，> 1 mg/L）。肺炎克雷伯菌对厄他培南不敏感的情况最常见于带有 ESBL 或 AmpC 基因的 OmpK36 变异体。确定适当抗菌疗法的监测策略应包括所有主要传染性耐药基因的基因型-表型关系以及肺炎克雷伯菌等生物体中相关孔蛋白突变的特征。
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 beta-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 (bla(TEM), n = 33; plasmid AmpC, n = 69; extended-spectrum beta-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 beta-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.