BACKGROUND:Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired "hypervirulent" strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. METHODS:We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool. RESULTS:K. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae. CONCLUSIONS:K. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance-reporting full molecular profiles including STs, AMR, virulence and serotype locus information-can help standardise comparisons between sites and identify regional differences in pathogen populations.

译文

背景:肺炎克雷伯菌是引起血液感染(BSI)的主要原因。产生广谱β-内酰胺酶(ESBLs)或碳青霉烯酶的菌株被认为是全球重点病原体,由于严重的治疗选择有限,因此迫切需要新的治疗和预防策略。南亚和东南亚地区是抗药性(AMR)肺炎克雷伯氏菌以及典型的抗微生物药敏性,社区获得的“高毒力”菌株的主要枢纽。高毒力AMR菌株的出现和胞外多糖多样性数据的缺乏对全球肺炎克雷伯氏菌BSI控制策略提出了挑战。
方法:我们对来自南亚和东南亚的七个主要医疗机构的365例BSI肺炎克雷伯氏菌进行了回顾性基因组流行病学研究,使用肺炎克雷伯菌特异性Kleborate提取临床相关信息(AMR,毒力,K和O抗原基因座)。基因组分型工具。
结果:K。肺炎BSI分离株高度多样化,包括120个多基因座序列类型(ST)和63 K个基因座。 ESBL和碳青霉烯酶基因频率分别为47%和17%。在28%的分离物中检测到与高毒力相关的航空细菌素合成位点(iuc)。重要的是,有7%的分离株带有iuc加上ESBL和/或碳青霉烯酶基因。后者代表基因型AMR毒力收敛,通常被认为是一种罕见现象,但在南亚BSI中尤为普遍(17%)。最令人担忧的是,我们鉴定了同时携带iuc和AMR基因的七个新型质粒,从而提高了这些表型在肺炎克雷伯菌之间共转移的前景。
结论:K。南亚和东南亚的肺炎BSI是由与其他地区不同的ST引起的,并且获得性毒力决定因素的频率更高。同时检测到同时携带iuc和AMR基因的肺炎克雷伯氏菌的检出率也高于其他地方。这项研究表明,基于基因组的监测报告全分子概况(包括ST,AMR,毒力和血清型基因座信息)如何帮助标准化站点之间的比较并确定病原体种群的区域差异。

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