Department of Respiratory & Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China.
Chin Med J (Engl). 2012 Mar;125(5):894-900.
The extended spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the major pathogens causing pneumonia and have a significant impact on the clinical course. Limited data exist on molecular characterization of ESBL-producing E. coli and K. pneumoniae that cause pneumonia. The aim of this study was to investigate the comprehensive multilevel characteristics of E. coli and K. pneumoniae causing pneumonia in China for the first time.
E. coli (17) and K. pneumoniae (21) isolates responsible for pneumonia were isolated from 1270 specimens collected in a prospective multi-center study in eight teaching hospitals in China from June to December in 2007. The susceptibilities, ESBL confirmation, sequence typing, blaCTX-M and blaSHV genes, their genetic environment and plasmid Inc/rep types were determined.
Sixteen E. coli (94.1%) and eleven K. pneumoniae (52.4%) isolates were ESBL producers. About 77.8% and 66.7% of them were resistance to ciprofloxacin and levofloxacin, and 100% were susceptible to imipenem. The most prevalent ESBL gene was CTX-M-14, followed by SHV-2, CTX-M-15, CTX-M-3, CTX-M-65, SHV-12, SHV-26 and SHV-28. SHV-1 and SHV-11 were also detected and coexisted with blaCTX-Ms in five strains, and three strains contained only SHV-1. All CTX-M-14 were detected ISEcp1 upstream and nine were found IS903 downstream and the majority of them (64.3%) were carried by IncF plasmids. All blaSHV were flanked by recF and deoR, located on IncF, IncN, IncX and IncH plasmids. Two SHV-2, one SHV-1 and the only SHV-28 were further preceded by IS26. Genes lacY and lacZ were detected at further upstream of two blaSHV-1. The K. pneumoniae carrying SHV-28 was susceptible to β-lactams, and no mutations or deletions in gene or promoter sequences were identified to account for susceptibility. Multilocus sequence typing experiments showed the ESBL-producing strains were genetically diverse.
The rate of occurrence of blaESBL in E. coli and K. pneumoniae causing pneumonia was high, and blaCTX-M-14 was dominant and probably mobilized by ISEcp1 mainly on IncF plasmids. Importantly, unexpressed blaESBL genes may occur in susceptible isolates and hence may have clinical implications.
产超广谱β-内酰胺酶（ESBL）的大肠杆菌（E. coli）和肺炎克雷伯菌（K. pneumoniae）是引起肺炎的主要病原体，对临床病程有重大影响。关于引起肺炎的产 ESBL 的大肠杆菌和肺炎克雷伯菌的分子特征的资料有限。本研究的目的是首次在中国调查引起肺炎的大肠杆菌和肺炎克雷伯菌的综合多层次特征。
2007 年 6 月至 12 月，从中国 8 所教学医院的前瞻性多中心研究的 1270 份标本中分离出 17 株大肠杆菌和 21 株肺炎克雷伯菌引起的肺炎。测定了药敏、ESBL 确证、序列分型、blaCTX-M 和 blaSHV 基因、其遗传环境和质粒 Inc/rep 类型。
16 株大肠杆菌（94.1%）和 11 株肺炎克雷伯菌（52.4%）为 ESBL 产酶菌。其中约 77.8%和 66.7%对环丙沙星和左氧氟沙星耐药，100%对亚胺培南敏感。最常见的 ESBL 基因是 CTX-M-14，其次是 SHV-2、CTX-M-15、CTX-M-3、CTX-M-65、SHV-12、SHV-26 和 SHV-28。还检测到 SHV-1 和 SHV-11，并在 5 株菌中与 blaCTX-Ms 共存，3 株菌中仅存在 SHV-1。所有 CTX-M-14 均在上游检测到 ISEcp1，9 株在下游检测到 IS903，其中大多数（64.3%）由 IncF 质粒携带。所有 blaSHV 均由 recF 和 deoR 侧翼，位于 IncF、IncN、IncX 和 IncH 质粒上。两个 SHV-2、一个 SHV-1 和唯一的 SHV-28 进一步由 IS26 前导。两个 blaSHV-1 的上游进一步检测到 lacY 和 lacZ 基因。携带 SHV-28 的肺炎克雷伯菌对β-内酰胺类药物敏感，基因或启动子序列中未发现导致敏感性的突变或缺失。多位点序列分型实验表明，产 ESBL 株具有遗传多样性。
引起肺炎的大肠杆菌和肺炎克雷伯菌中 blaESBL 的发生率较高，blaCTX-M-14 为主导，可能主要通过 ISEcp1 移动到 IncF 质粒上。重要的是，敏感分离株中可能存在未表达的 blaESBL 基因，因此可能具有临床意义。
