Mena Ana, Plasencia Virginia, García Laura, Hidalgo Olga, Ayestarán José Ignacio, Alberti Sebastián, Borrell Nuria, Pérez José L, Oliver Antonio
Servicio de Microbiología, Hospital Son Dureta and Instituto Universitario de Investigación en Ciencias de la Salud, Palma de Mallorca, Spain.
J Clin Microbiol. 2006 Aug;44(8):2831-7. doi: 10.1128/JCM.00418-06.
All extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolates from patients admitted to and adult intensive care unit were prospectively documented from 2002 to 2005, when a large outbreak (51 patients affected) of multiresistant ESBL-producing Klebsiella pneumoniae infection was detected. The involvement of a single K. pneumoniae clone was demonstrated by pulsed-field gel electrophoresis. In addition to the ESBL-mediated resistance, the epidemic strain uniformly showed cross-resistance to ciprofloxacin, gentamicin, tobramycin, trimethoprim-sulfamethoxazole, and tetracycline, whereas resistance to the beta-lactam-beta-lactamase inhibitor combinations was variable. The ESBL involved was CTX-M-1, as demonstrated by isoelectric focusing, PCR amplification, and sequencing. CTX-M-1 as well as the aminoglycoside resistance determinants were encoded in a 50-kb plasmid that could be transferred to Escherichia coli only by transformation. In two of the infected patients, carbapenem resistance development (MICs of 8 to 12, 16, and >32 microg/ml for imipenem, meropenem, and ertapenem, respectively) was documented, both in clinical samples and in intestinal colonization studies. The analysis of the outer membrane proteins of the carbapenem-susceptible and -resistant isolates revealed that the former expressed only one of the two major porins, OmpK36, whereas the latter did not express either of them. In one of the cases, the lack of expression of OmpK36 was demonstrated to be mediated by the interruption of the coding sequence by the insertion sequence IS26. This is the first report of a large outbreak of CTX-M-1-producing Enterobacteriaceae and, curiously, the first documented description in the literature of CTX-M-1 in K. pneumoniae, despite the fact that this enzyme has been found in multiple species. Furthermore, we document and characterize for the first time carbapenem resistance development in CTX-M-1-producing Enterobacteriaceae.
2002年至2005年期间，对入住成人重症监护病房患者中所有产超广谱β-内酰胺酶（ESBL）的肠杆菌科分离株进行了前瞻性记录，期间检测到一起由产多重耐药ESBL肺炎克雷伯菌引起的大规模暴发（累及51例患者）。脉冲场凝胶电泳证明此次暴发涉及单一的肺炎克雷伯菌克隆。除了ESBL介导的耐药性外，流行菌株一致表现出对环丙沙星、庆大霉素、妥布霉素、甲氧苄啶-磺胺甲恶唑和四环素的交叉耐药，而对β-内酰胺-β-内酰胺酶抑制剂组合的耐药性则有所不同。通过等电聚焦、PCR扩增和测序证明，所涉及的ESBL为CTX-M-1。CTX-M-1以及氨基糖苷类耐药决定簇编码于一个50kb的质粒上，该质粒只能通过转化转移至大肠杆菌。在两名感染患者中，临床样本和肠道定植研究均记录到碳青霉烯类耐药性的产生（亚胺培南、美罗培南和厄他培南的MIC分别为8至12、16和>32μg/ml）。对碳青霉烯类敏感和耐药分离株的外膜蛋白分析显示，前者仅表达两种主要孔蛋白之一OmpK36，而后者两种孔蛋白均未表达。在其中一例中，证明OmpK36缺乏表达是由插入序列IS26中断编码序列介导的。这是关于产CTX-M-1肠杆菌科大规模暴发的首次报道，奇怪的是，尽管该酶已在多个菌种中发现，但这是文献中首次记录的肺炎克雷伯菌中CTX-M-1的描述。此外，我们首次记录并描述了产CTX-M-1肠杆菌科中碳青霉烯类耐药性的产生。
