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从英国和威尔士输入性肠热病病例中分离出的产 ESBL 菌株显示,多重耐药伤寒沙门氏菌 XDR 中 blaCTX-M-15 基因位于染色体上的多个整合子内。

ESBL-producing strains isolated from imported cases of enteric fever in England and Wales reveal multiple chromosomal integrations of blaCTX-M-15 in XDR Salmonella Typhi.

机构信息

Gastrointestinal Bacteria Reference Unit, National Infection Service, Public Health England, London, UK.

Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.

出版信息

J Antimicrob Chemother. 2021 May 12;76(6):1459-1466. doi: 10.1093/jac/dkab049.

DOI:10.1093/jac/dkab049
PMID:33704480
Abstract

BACKGROUND

There are approximately 300 cases of enteric fever reported annually from England and Wales; most are imported infections. Clinical management of enteric fever remains a challenge with the emergence of ESBL-producing strains, especially XDR Salmonella Typhi from Sindh, Pakistan.

METHODS

All strains of S. Typhi and Salmonella Paratyphi A isolated from cases presenting with symptoms of enteric fever in England and Wales, between 1 April 2014 and 31 March 2020, were characterized using WGS. Antibiotic susceptibility testing was performed using an agar dilution method.

RESULTS

ESBL strains contributed to 69 cases of enteric fever (S. Typhi n = 68, S. Paratyphi A n = 1); 68 were imported (Pakistan n = 64, Iraq n = 2, Bangladesh n = 1 and India n = 1). Ages ranged from 1 to 56 years, 36/69 (52%) were children, 52% were female and the duration of hospital stay ranged from 1 to 23 days. The ESBL phenotype was conferred by the presence of blaCTX-M-15 (S. Typhi n = 67 and S. Paratyphi A n = 1) or blaCTX-M-55 (S. Typhi n = 1). An IncY plasmid harbouring blaCTX-M-15 and qnr was detected in 56 strains from Pakistan. The IncY plasmid was absent in the remaining strains and there was evidence of a 4 kb ISEcpl-blaCTX-M-15-tnp gene cassette insertion into the chromosome at one of three integration points.

CONCLUSIONS

Chromosomal integration of blaCTX-M-15 within the XDR Sindh strains may lead to the maintenance of resistance in the absence of antibiotic selection pressure. Empirical treatment of cases of complicated enteric fever returning from Pakistan will henceforth have to include a carbapenem.

摘要

背景

据报道,英格兰和威尔士每年约有 300 例肠热病病例;大多数是输入性感染。肠热病的临床治疗仍然是一个挑战,特别是来自巴基斯坦信德省的产超广谱β-内酰胺酶(ESBL)的耐多药伤寒沙门氏菌和副伤寒沙门氏菌 A。

方法

从 2014 年 4 月 1 日至 2020 年 3 月 31 日期间,在英格兰和威尔士出现肠热病症状的病例中分离出的所有伤寒沙门氏菌和副伤寒沙门氏菌 A 菌株均采用 WGS 进行特征描述。采用琼脂稀释法进行抗生素敏感性试验。

结果

ESBL 菌株导致 69 例肠热病(伤寒沙门氏菌 n = 68,副伤寒沙门氏菌 A n = 1);68 例为输入性感染(巴基斯坦 n = 64,伊拉克 n = 2,孟加拉国 n = 1,印度 n = 1)。年龄范围为 1 至 56 岁,69 例中有 36 例(52%)为儿童,52%为女性,住院时间范围为 1 至 23 天。ESBL 表型由 blaCTX-M-15(伤寒沙门氏菌 n = 67,副伤寒沙门氏菌 A n = 1)或 blaCTX-M-55(伤寒沙门氏菌 n = 1)的存在赋予。在来自巴基斯坦的 56 株菌中检测到携带 blaCTX-M-15 和 qnr 的 IncY 质粒。在其余菌株中未检测到 IncY 质粒,并且有证据表明在三个整合点之一处,染色体上存在 4kb 的 ISEcpl-blaCTX-M-15-tnp 基因盒插入。

结论

XDR 信德省菌株中 blaCTX-M-15 的染色体整合可能导致在没有抗生素选择压力的情况下维持耐药性。因此,对于从巴基斯坦返回的复杂肠热病病例,经验性治疗必须包括碳青霉烯类药物。

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