Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India; Department of Biosciences, Integral University, Lucknow, India.
Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India.
Int J Antimicrob Agents. 2014 Jul;44(1):30-7. doi: 10.1016/j.ijantimicag.2014.03.003. Epub 2014 Apr 24.
The growing prevalence of carbapenem resistance in Enterobacteriaceae worldwide is a major concern. New Delhi metallo-β-lactamase (NDM)-mediated carbapenem resistance has been identified in Enterobacteriaceae from numerous countries including those of the Indian subcontinent. Currently, seven NDM β-lactamase variants (NDM-1 to -7) have been identified. This study evaluated the detection and molecular characterisation of NDM variants in Enterobacteriaceae at a tertiary care hospital in India. A total of 464 isolates were tested; 57 (12.3%) were resistant or showed reduced susceptibility to imipenem and meropenem. All carbapenem-resistant isolates were blaNDM-positive by PCR, but 13 isolates bore variants that differed in sequence from blaNDM-1. NDM-5, NDM-6 and NDM-7 were identified in two, eight and three isolates, respectively. blaNDM variants were located on plasmids of >100kb with IncF, IncA/C and untypeable replicon types. Genes encoding the 16S rRNA methyltransferases RmtB, RmtC and ArmA as well as those for AmpC β-lactamases were also located on the same plasmids as blaNDM in different combinations. The prevalence of NDM-5 to -7 variants was significantly higher in Escherichia coli (P=0.015) and they were more frequently isolated from the urology ward (P=0.037) than NDM-1. The mortality rate was comparable between patients infected with isolates positive for blaNDM-1 and blaNDM variants [25% (11/44) vs. 23% (3/13)]. Expression of blaNDM variants in E. coli using the same promoter showed that NDM-7 conferred higher resistance to imipenem. The diverse genotypic features of blaNDM indicate rapid evolution of NDM resulting from their wide spread in the Indian subcontinent.
全球范围内肠杆菌科中产碳青霉烯酶的流行率不断上升，这是一个主要关注点。新德里金属β-内酰胺酶（NDM）介导的碳青霉烯类耐药性已在包括印度次大陆在内的许多国家的肠杆菌科中被发现。目前，已经鉴定出 7 种 NDM β-内酰胺酶变体（NDM-1 至 -7）。本研究评估了在印度一家三级护理医院的肠杆菌科中 NDM 变体的检测和分子特征。共检测了 464 株分离株；57 株（12.3%）对亚胺培南和美罗培南耐药或显示出降低的敏感性。所有碳青霉烯类耐药分离株的 PCR 均为 blaNDM 阳性，但 13 株分离株的序列与 blaNDM-1 不同。在 2、8 和 3 株分离株中分别鉴定出 NDM-5、NDM-6 和 NDM-7。blaNDM 变体位于>100kb 的质粒上，具有 IncF、IncA/C 和未定型复制子类型。编码 16S rRNA 甲基转移酶 RmtB、RmtC 和 ArmA 的基因以及 AmpC β-内酰胺酶的基因也位于 blaNDM 所在的相同质粒上，但与 blaNDM 的组合不同。Escherichia coli 中 NDM-5 至 -7 变体的流行率明显更高（P=0.015），并且它们比 NDM-1 更频繁地从泌尿科病房分离出来（P=0.037）。感染 blaNDM-1 和 blaNDM 变体阳性分离株的患者的死亡率相当[25%（11/44）比 23%（3/13）]。使用相同启动子在大肠杆菌中表达 blaNDM 变体表明，NDM-7 对亚胺培南的耐药性更高。blaNDM 的多样化基因型特征表明，由于其在印度次大陆的广泛传播，NDM 迅速进化。
