Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce. A retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018. During this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p < 0.001 and OR 2.3, p < 0.05, respectively).The presence of each blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p < 0.001; OR 14.2, p < 0.001 and OR 1.3, p < 0.05 respectively) and being MDR (OR 1.96, p < 0.001; OR 5.9, p < 0.001 and OR 2.3, p < 0.001 respectively). This study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis.

中文翻译：

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尼泊尔三级医院的多药耐药革兰氏阴性菌患病率很高，且广谱β-内酰胺酶（ESBL）和碳青霉烯酶编码基因的分布广泛

与革兰氏阴性菌中的广谱β-内酰胺酶（ESBLs）和碳青霉烯酶相关的多药耐药性（MDR）和广泛耐药性（XDR）是全球公共卫生问题。关于来自尼泊尔的革兰氏阴性细菌中循环抗药性（AMR）基因及其与MDR和ESBL表型的相关性的数据很少。进行了一项回顾性研究，调查了大肠杆菌，克雷伯菌属，肠杆菌属中ESBL和碳青霉烯酶基因的分布及其与ESBL和MDR表型的潜在关联。和不动杆菌属。在2012年至2018年之间，在尼泊尔加德满都的一家大型三级医院进行了分离。在此期间，该医院分离了719株大肠杆菌，532克雷伯菌属，520肠杆菌属。和382不动杆菌属; 1955/2153（90。1％的分离株是MDR，一半（1080/2153）是ESBL生产者。PCR扩增后，blaTEM（1281/1771; 72％），blaCTXM-1（930/1771; 53％）和blaCTXM-8（419/1771; 24％）是肠杆菌中最普遍的ESBL基因。BlaOXA和blaOXA-51是肠杆菌（918/1771； 25％）和不动杆菌属中最常见的blaOXA家族基因。（218/382; 57％）。所有分离株中有16％（342/2153）和20％（357/1771）的肠杆菌具有blaNDM-1和blaKPC碳青霉烯酶基因。肠杆菌属肠杆菌属。blaKPC基因最常呈阳性（201/337； 60％）。每种blaCTX-M和blaOXA的存在与对第三代头孢菌素的不敏感性显着相关（分别为OR 14.7，p <0.001和OR 2.3，p <0.05）。blaCTXM和blaOXA家族基因与ESBL阳性率显着相关（OR 2.96，p <0.001; OR 14.2，p <0.001和OR 1.3，p <0.05）和MDR（OR 1.96，p <0.001; OR 5.9，p < 0.001和OR 2.3，分别为p <0.001）。这项研究记录了在我们的临床环境中，ADR令人震惊，MDR ESBL和碳青霉烯酶阳性ESKAPE微生物的患病率很高。这些数据表明，感染患者的临床管理越来越困难，需要使用最后使用的抗菌剂，这反过来可能会加剧全球AMR危机的严重性。p <0.001和OR 2.3，p <0.001）。这项研究记录了在我们的临床环境中，ADR令人震惊，MDR ESBL和碳青霉烯酶阳性ESKAPE微生物的患病率很高。这些数据表明，感染患者的临床管理越来越困难，需要使用最后使用的抗菌剂，这反过来可能会加剧全球AMR危机的严重性。p <0.001和OR 2.3，p <0.001）。这项研究记录了在我们的临床环境中，ADR令人震惊，MDR ESBL和碳青霉烯酶阳性ESKAPE微生物的患病率很高。这些数据表明，感染患者的临床管理越来越困难，需要使用最后使用的抗菌剂，这反过来可能会加剧全球AMR危机的严重性。