{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:46:01Z","timestamp":1778604361975,"version":"3.51.4"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002141","name":"Public Health England","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Institute Strategic Programme Microbes in the Food Chain","award":["BB\/R012504\/1"],"award-info":[{"award-number":["BB\/R012504\/1"]}]},{"name":"Institute Strategic Programme Microbes in the Food Chain","award":["BBS\/E\/F\/000PR10348"],"award-info":[{"award-number":["BBS\/E\/F\/000PR10348"]}]},{"name":"Health Protection Research Unit"},{"name":"National Institute of Health Research (NIHR) UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ESBL strains contributed to 69 cases of enteric fever (S. Typhi n\u2009=\u200968, S. Paratyphi A n\u2009=\u20091); 68 were imported (Pakistan n\u2009=\u200964, Iraq n\u2009=\u20092, Bangladesh n\u2009=\u20091 and India n\u2009=\u20091). Ages ranged from 1 to 56\u2009years, 36\/69 (52%) were children, 52% were female and the duration of hospital stay ranged from 1 to 23\u2009days. The ESBL phenotype was conferred by the presence of blaCTX-M-15 (S. Typhi n\u2009=\u200967 and S. Paratyphi A n\u2009=\u20091) or blaCTX-M-55 (S. Typhi n\u2009=\u20091). 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\u2009kb ISEcpl-blaCTX-M-15-tnp gene cassette insertion into the chromosome at one of three integration points.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab049","type":"journal-article","created":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T20:51:52Z","timestamp":1613076712000},"page":"1459-1466","source":"Crossref","is-referenced-by-count":42,"title":["ESBL-producing strains isolated from imported cases of enteric fever in England and Wales reveal multiple chromosomal integrations of <i>bla<\/i>CTX-M-15 in XDR <i>Salmonella<\/i> Typhi"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7297-1485","authenticated-orcid":false,"given":"Satheesh","family":"Nair","sequence":"first","affiliation":[{"name":"Gastrointestinal Bacteria Reference Unit, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Chattaway","sequence":"additional","affiliation":[{"name":"Gastrointestinal Bacteria Reference Unit, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma C","family":"Langridge","sequence":"additional","affiliation":[{"name":"Quadram Institute Bioscience, Norwich Research Park, Norwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Gentle","sequence":"additional","affiliation":[{"name":"Gastrointestinal Bacteria Reference Unit, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Day","sequence":"additional","affiliation":[{"name":"Gastrointestinal Bacteria Reference Unit, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma V","family":"Ainsworth","sequence":"additional","affiliation":[{"name":"Quadram Institute Bioscience, Norwich Research Park, Norwich, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Travel Health and International Health Regulations, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Smith","sequence":"additional","affiliation":[{"name":"Communicable Disease Surveillance Centre, Public Health Wales, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Gastrointestinal Pathogens Department, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J","family":"Dallman","sequence":"additional","affiliation":[{"name":"Gastrointestinal Bacteria Reference Unit, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gauri","family":"Godbole","sequence":"additional","affiliation":[{"name":"Gastrointestinal Pathogens Department, National Infection Service, Public Health England, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"2021051408575321400_dkab049-B1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1086\/649541","article-title":"Global trends in typhoid and paratyphoid fever","volume":"50","author":"Crump","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2021051408575321400_dkab049-B2"},{"key":"2021051408575321400_dkab049-B3","doi-asserted-by":"crossref","first-page":"e0007620","DOI":"10.1371\/journal.pntd.0007620","article-title":"Informal genomic surveillance of regional distribution of Salmonella Typhi genotypes and antimicrobial resistance via returning travellers","volume":"13","author":"Ingle","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"2021051408575321400_dkab049-B4","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1093\/cid\/ciy032","article-title":"First report of CTX-M-15 Salmonella Typhi from England","volume":"66","author":"Godbole","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2021051408575321400_dkab049-B5","doi-asserted-by":"crossref","first-page":"e00105-18","DOI":"10.1128\/mBio.00105-18","article-title":"Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins","volume":"9","author":"Klemm","year":"2018","journal-title":"mBio"},{"key":"2021051408575321400_dkab049-B6","doi-asserted-by":"crossref","first-page":"6432580","DOI":"10.1155\/2020\/6432580","article-title":"Extensively drug-resistant (XDR) typhoid: evolution, prevention, and its management","volume":"2020","author":"Akram","year":"2020","journal-title":"Biomed Res Int"},{"key":"2021051408575321400_dkab049-B7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S1473-3099(19)30176-8","article-title":"Ceftriaxone-resistant Salmonella Typhi in a traveller returning from a mass gathering in Iraq","volume":"19","author":"Godbole","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2021051408575321400_dkab049-B8","doi-asserted-by":"crossref","first-page":"e0228250","DOI":"10.1371\/journal.pone.0228250","article-title":"Genomic surveillance detects Salmonella enterica serovar Paratyphi A harbouring blaCTX-M-15 from a traveller returning from Bangladesh","volume":"15","author":"Nair","year":"2020","journal-title":"PLoS One"},{"key":"2021051408575321400_dkab049-B9","year":"2020"},{"key":"2021051408575321400_dkab049-B10","doi-asserted-by":"crossref","first-page":"3400","DOI":"10.1093\/jac\/dkw318","article-title":"WGS for surveillance of antimicrobial resistance: a pilot study to detect the prevalence and mechanism of resistance to azithromycin in a UK population of non-typhoidal Salmonella","volume":"71","author":"Nair","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2021051408575321400_dkab049-B11","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/jac\/dkw371","article-title":"Antimicrobial resistance in Shiga toxin-producing Escherichia coli serogroups O157 and O26 isolated from human cases of diarrhoeal disease in England, 2015","volume":"72","author":"Day","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2021051408575321400_dkab049-B12","year":"2020"},{"key":"2021051408575321400_dkab049-B13","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/jac\/dkx379","article-title":"Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of Salmonella enterica serovars Typhi and Paratyphi","volume":"73","author":"Day","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2021051408575321400_dkab049-B14","doi-asserted-by":"crossref","first-page":"e2308","DOI":"10.7717\/peerj.2308","article-title":"MOST: a modi\ufb01ed MLST typing tool based on short read sequencing","volume":"4","author":"Tewolde","year":"2016","journal-title":"PeerJ"},{"key":"2021051408575321400_dkab049-B15","year":"2020"},{"key":"2021051408575321400_dkab049-B16","doi-asserted-by":"crossref","first-page":"12827","DOI":"10.1038\/ncomms12827","article-title":"An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid","volume":"7","author":"Wong","year":"2016","journal-title":"Nat Commun"},{"key":"2021051408575321400_dkab049-B17","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.3390\/microorganisms8091336","article-title":"Emergence of resistance to fluoroquinolones and third-generation cephalosporins in Salmonella Typhi in Lahore, Pakistan","volume":"8","author":"Rasheed","year":"2020","journal-title":"Microorganisms"},{"key":"2021051408575321400_dkab049-B18","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2021051408575321400_dkab049-B19","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"2021051408575321400_dkab049-B20","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res"},{"key":"2021051408575321400_dkab049-B21","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1093\/bioinformatics\/bty212","article-title":"SnapperDB: a database solution for routine sequencing analysis of bacterial isolates","volume":"34","author":"Dallman","year":"2018","journal-title":"Bioinformatics"},{"key":"2021051408575321400_dkab049-B22","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1093\/nar\/gku1196","article-title":"Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins","volume":"43","author":"Croucher","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2021051408575321400_dkab049-B23","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/bioinformatics\/btu033","article-title":"RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies","volume":"30","author":"Stamatakis","year":"2014","journal-title":"Bioinformatics"},{"key":"2021051408575321400_dkab049-B24","doi-asserted-by":"crossref","first-page":"618","DOI":"10.15585\/mmwr.mm6920a2","article-title":"Update on extensively drug-resistant Salmonella serotype Typhi infections among travelers to or from Pakistan and report of ceftriaxone-resistant Salmonella serotype Typhi infections among travelers to Iraq - United States, 2018-2019","volume":"69","author":"Fran\u00e7ois Watkins","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2021051408575321400_dkab049-B25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jinf.2009.11.009","article-title":"Enteric fever in a UK regional infectious diseases unit: a 10 year retrospective review","volume":"60","author":"Clark","year":"2010","journal-title":"J Infect"},{"key":"2021051408575321400_dkab049-B26"},{"key":"2021051408575321400_dkab049-B27","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.3389\/fmicb.2019.01268","article-title":"The emergence of chromosomally located blaCTX-M-55 in Salmonella from foodborne animals in China","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Microbiol"},{"key":"2021051408575321400_dkab049-B28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jgar.2018.11.006","article-title":"Characterisation of chromosomally-located blaCTX-M and its surrounding sequence in CTX-M-type extended-spectrum \u03b2-lactamase-producing Escherichia coli isolates","volume":"17","author":"Hamamoto","year":"2019","journal-title":"J Glob Antimicrob Resist"},{"key":"2021051408575321400_dkab049-B29","doi-asserted-by":"crossref","first-page":"e0007868","DOI":"10.1371\/journal.pntd.0007868","article-title":"Molecular mechanism of azithromycin resistance among typhoidal Salmonella strains in Bangladesh identified through passive pediatric surveillance","volume":"13","author":"Hooda","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"2021051408575321400_dkab049-B30","doi-asserted-by":"crossref","first-page":"e00215-20","DOI":"10.1128\/mSphere.00215-20","article-title":"A race against time: reduced azithromycin susceptibility in Salmonella enterica serovar Typhi in Pakistan","volume":"5","author":"Iqbal","year":"2020","journal-title":"mSphere"},{"key":"2021051408575321400_dkab049-B31","first-page":"Doc01","article-title":"Relapse of typhoid fever following delayed response to meropenem: a case report and review of previously published cases indicating limited clinical efficacy of meropenem for the treatment of typhoid fever","volume":"17","author":"Blumentrath","year":"2019","journal-title":"Ger Med Sci"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/6\/1459\/37927482\/dkab049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/6\/1459\/37927482\/dkab049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T09:00:19Z","timestamp":1620982819000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/76\/6\/1459\/6168023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,10]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3,10]]},"published-print":{"date-parts":[[2021,5,12]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab049","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6,1]]},"published":{"date-parts":[[2021,3,10]]}}}