Nuffield Department of Clinical Medicine and the National Institute for Health Research Oxford Biomedical Research Centre (NIHR-OxBRC), University of Oxford, Oxford, UK.
Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, The Ronald Ross Building, 8 West Derby Street, Liverpool, L69 7BE, UK.
BMC Microbiol. 2019 Mar 12;19(1):59. doi: 10.1186/s12866-019-1431-9.
Extended-spectrum cephalosporin resistance (ESC-R) in Escherichia coli and Klebsiella pneumoniae is a healthcare threat; high gastrointestinal carriage rates are reported from South-east Asia. Colonisation prevalence data in Cambodia are lacking. The aim of this study was to determine gastrointestinal colonisation prevalence of ESC-resistant E. coli (ESC-R-EC) and K. pneumoniae (ESC-R-KP) in Cambodian children/adolescents and associated socio-demographic risk factors; and to characterise relevant resistance genes, their genetic contexts, and the genetic relatedness of ESC-R strains using whole genome sequencing (WGS).
Faeces and questionnaire data were obtained from individuals < 16 years in north-western Cambodia, 2012. WGS of cultured ESC-R-EC/KP was performed (Illumina). Maximum likelihood phylogenies were used to characterise relatedness of isolates; ESC-R-associated resistance genes and their genetic contexts were identified from de novo assemblies using BLASTn and automated/manual annotation. 82/148 (55%) of children/adolescents were ESC-R-EC/KP colonised; 12/148 (8%) were co-colonised with both species. Independent risk factors for colonisation were hospitalisation (OR: 3.12, 95% CI [1.52-6.38]) and intestinal parasites (OR: 3.11 [1.29-7.51]); school attendance conferred decreased risk (OR: 0.44 [0.21-0.92]. ESC-R strains were diverse; the commonest ESC-R mechanisms were bla 1 and 9 sub-family variants. Structures flanking these genes were highly variable, and for bla frequently involved IS26. Chromosomal bla integration was common in E. coli.
Gastrointestinal ESC-R-EC/KP colonisation is widespread in Cambodian children/adolescents; hospital admission and intestinal parasites are independent risk factors. The genetic contexts of bla are highly mosaic, consistent with rapid horizontal exchange. Chromosomal integration of bla may result in stable propagation in these community-associated pathogens.
大肠埃希菌和肺炎克雷伯菌对广谱头孢菌素的耐药性(ESC-R)是一种医疗保健威胁;东南亚报道的胃肠道携带率很高。柬埔寨缺乏殖民化流行率数据。本研究旨在确定柬埔寨儿童和青少年胃肠道 ESC-R 大肠杆菌(ESC-R-EC)和肺炎克雷伯菌(ESC-R-KP)的殖民化流行率以及相关的社会人口学危险因素;并使用全基因组测序(WGS)来描述相关的耐药基因、它们的遗传背景以及 ESC-R 菌株的遗传相关性。
2012 年在柬埔寨西北部从<16 岁的个体中获得粪便和问卷调查数据。对培养的 ESC-R-EC/KP 进行了 WGS(Illumina)。最大似然系统发育树用于描述分离株的相关性;使用 BLASTn 和自动/手动注释从从头组装中鉴定出 ESC-R 相关的耐药基因及其遗传背景。148 名儿童和青少年中有 82 名(55%)为 ESC-R-EC/KP 定植;12 名(8%)同时定植两种菌。定植的独立危险因素是住院(OR:3.12,95%CI [1.52-6.38])和肠道寄生虫(OR:3.11 [1.29-7.51]);上学则降低了风险(OR:0.44 [0.21-0.92])。ESC-R 株系多样;最常见的 ESC-R 机制是 bla1 和 9 亚家族的变体。这些基因侧翼的结构高度可变,bla 基因经常涉及 IS26。大肠杆菌中染色体 bla 的整合很常见。
柬埔寨儿童和青少年胃肠道 ESC-R-EC/KP 定植广泛;住院和肠道寄生虫是独立的危险因素。bla 的遗传背景高度镶嵌,与快速水平交换一致。bla 染色体的整合可能导致这些社区相关病原体的稳定传播。