Lancet infectious diseases 2023
要約
・広範囲耐性赤痢菌(S. flexneri血清型2 XDR)の検出が2021年以降、英国MSMの集団で増加している。
・XDRのS. flexneriはプラスミドにコードされたbla-CTX-M27を保有し、これはXDRのS. sonneiのプラスミドと類似している。
・XDRのS. sonneiとXDRのS. flexneriのアウトブレイクは地理的時間的分布が一致しており水平伝播を示唆する。
Summary
Background
Shigellosis, also known as bacillary dysentery, is caused by Shigella spp that spread through fecal–oral contact and was traditionally associated with international travel in England. However, sexual transmission of Shigella flexneri and Shigella sonnei among gay, bisexual, and other men who have sex with men (MSM) is now common. In September, 2021, emergence of extensively drug-resistant (XDR) S sonnei harbouring plasmid-encoded blaCTX-M-27 raised concerns over further spread of this extended-spectrum β-lactamase-producing gene. Using national surveillance in England, we identified and characterised isolates of S flexneri harbouring blaCTX-M-27.
Methods
In this epidemiological study, we identified and phylogenetically characterised S flexneri isolates harbouring blaCTX-M-27 that were referred to the Gastrointestinal Bacterial Reference Unit (GBRU) at the UK Health Security Agency. All isolates referred to the GBRU undergo whole-genome sequencing, enabling antimicrobial resistance determination using genetic markers. Cases were defined as individuals diagnosed with S flexneri harbouring blaCTX-M-27 in England, with a specimen date between Sept 1, 2015, and June 12, 2022, who were phylogenetically confirmed as part of two t10 (approximately ten single nucleotide polymorphisms) clusters. Long-read sequencing elucidated the genomic location of blaCTX-M-27. Laboratory data, integrated with available demographic and clinical information from patient questionnaires, were summarised using descriptive statistics.
Findings
A sustained increase in cases of S flexneri harbouring blaCTX-M-27 (n=26) occurred from September, 2021, having been sporadically reported (n=11) in the preceding 6 years. blaCTX-M-27 acquisition events within S flexneri 2a established an XDR paraphyletic (n=8) cluster and a multidrug-resistant monophyletic (n=18) cluster. Cases were among adult male individuals (median age 37 years [IQR 31–46]) and, of the 13 individuals who completed a patient questionnaire, ten (77%) identified as MSM. Antimicrobial treatment was received by seven (54%) of 13 individuals, and four (31%) individuals were admitted to hospital. The IncFII plasmids harbouring blaCTX-M-27 showed high similarity to the XDR S sonnei outbreak plasmid, with 82% and 99% nucleotide similarity between the cluster plasmids and the XDR S sonnei outbreak plasmid.
Interpretation
We report emergence of XDR and multidrug-resistant S flexneri 2a harbouring blaCTX-M-27 among MSM in England. Epidemiological and plasmid similarities with the XDR S sonnei outbreak support horizontal acquisition events, emphasising the importance of mobilisable antimicrobial resistance and the need for genomic-based surveillance.
Funding
National Institute for Health and Care Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency.
