{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:38:26Z","timestamp":1791887906702,"version":"4.3.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T00:00:00Z","timestamp":1550534400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["098051"],"award-info":[{"award-number":["098051"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"H3ABioNet","award":["U41HG006941"],"award-info":[{"award-number":["U41HG006941"]}]},{"name":"Food Standards Fellowship","award":["FS101185"],"award-info":[{"award-number":["FS101185"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n\u205f=\u205f66) and from outside sub-Saharan Africa (n\u205f=\u205f67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkz032","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T07:06:45Z","timestamp":1547449605000},"page":"1223-1232","source":"Crossref","is-referenced-by-count":60,"title":["Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7780-2173","authenticated-orcid":false,"given":"Patrick","family":"Musicha","sequence":"first","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK"},{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisomo L","family":"Msefula","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"},{"name":"College of Medicine, University of Malawi, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison E","family":"Mather","sequence":"additional","affiliation":[{"name":"Quadram Institute Bioscience, Norwich, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrispin","family":"Chaguza","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"},{"name":"Wellcome Sanger Institute, Hinxton, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K","family":"Cain","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"},{"name":"Liverpool School of Tropical Medicine, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikondi","family":"Peno","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1741-6486","authenticated-orcid":false,"given":"Teemu","family":"Kallonen","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Hinxton, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Khonga","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Malawi, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Denis","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J","family":"Gray","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S","family":"Heyderman","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R","family":"Thomson","sequence":"additional","affiliation":[{"name":"Quadram Institute Bioscience, Norwich, UK"},{"name":"London School of Tropical Medicine, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean B","family":"Everett","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"},{"name":"University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A","family":"Feasey","sequence":"additional","affiliation":[{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"},{"name":"Liverpool School of Tropical Medicine, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,18]]},"reference":[{"key":"2019121022375631100_dkz032-B1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.tim.2016.09.007","article-title":"Klebsiella pneumoniae population genomics and antimicrobial-resistant clones","volume":"24","author":"Wyres","year":"2016","journal-title":"Trends Microbiol"},{"key":"2019121022375631100_dkz032-B2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/CMR.11.4.589","article-title":"Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors","volume":"11","author":"Podschun","year":"1998","journal-title":"Clin Microbiol Rev"},{"key":"2019121022375631100_dkz032-B3","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01976-16","article-title":"Evolution and epidemiology of multidrug-resistant Klebsiella pneumoniae in the United Kingdom and Ireland","volume":"8","author":"Moradigaravand","year":"2017","journal-title":"MBio"},{"key":"2019121022375631100_dkz032-B4","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/S1473-3099(17)30394-8","article-title":"Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998-2016): a surveillance study","volume":"17","author":"Musicha","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2019121022375631100_dkz032-B5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1586\/eri.13.12","article-title":"Clinical relevance of the ESKAPE pathogens","volume":"11","author":"Pendleton","year":"2013","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2019121022375631100_dkz032-B6","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1179\/2046905513Y.0000000082","article-title":"Bloodstream infections and antimicrobial resistance patterns in a South African neonatal intensive care unit","volume":"34","author":"Morkel","year":"2014","journal-title":"Paediatr Int Child Health"},{"key":"2019121022375631100_dkz032-B7","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ijmm.2017.07.006","article-title":"Molecular epidemiology of Klebsiella pneumoniae invasive infections over a decade at Kilifi County Hospital in Kenya","volume":"307","author":"Henson","year":"2017","journal-title":"Int J Med Microbiol"},{"key":"2019121022375631100_dkz032-B8","article-title":"Emerging resistance to empiric antimicrobial regimens for pediatric bloodstream infections in Malawi (1998-2017)","author":"Iroh Tam","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2019121022375631100_dkz032-B9","doi-asserted-by":"crossref","first-page":"E3574","DOI":"10.1073\/pnas.1501049112","article-title":"Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health","volume":"112","author":"Holt","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"2019121022375631100_dkz032-B10","doi-asserted-by":"crossref","first-page":"e0133727.","DOI":"10.1371\/journal.pone.0133727","article-title":"Genomic analysis of the emergence and rapid global dissemination of the clonal group 258 Klebsiella pneumoniae pandemic","volume":"10","author":"Bowers","year":"2015","journal-title":"PLoS One"},{"key":"2019121022375631100_dkz032-B11","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.2217\/fmb.15.22","article-title":"The changing epidemiology of hospital outbreaks due to ESBL-producing Klebsiella pneumoniae: the CTX-M-15 type consolidation","volume":"10","author":"Calbo","year":"2015","journal-title":"Future Microbiol"},{"key":"2019121022375631100_dkz032-B12","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1093\/jac\/dkw321","article-title":"The spread of KPC-producing Enterobacteriaceae in Spain: WGS analysis of the emerging high-risk clones of Klebsiella pneumoniae ST11\/KPC-2, ST101\/KPC-2 and ST512\/KPC-3","volume":"71","author":"Oteo","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2019121022375631100_dkz032-B13","doi-asserted-by":"crossref","first-page":"227","DOI":"10.15252\/emmm.201404767","article-title":"A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae","volume":"7","author":"Chung The","year":"2015","journal-title":"EMBO Mol Med"},{"key":"2019121022375631100_dkz032-B14","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1093\/gbe\/evv062","article-title":"Extensive capsule locus variation and large-scale genomic recombination within the Klebsiella pneumoniae clonal group 258","volume":"7","author":"Wyres","year":"2015","journal-title":"Genome Biol Evol"},{"key":"2019121022375631100_dkz032-B15","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/j.1574-6976.2011.00268.x","article-title":"Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance","volume":"35","author":"Woodford","year":"2011","journal-title":"FEMS Microbiol Rev"},{"key":"2019121022375631100_dkz032-B16","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1101\/gr.074492.107","article-title":"Velvet: algorithms for de novo short read assembly using de Bruijn graphs","volume":"18","author":"Zerbino","year":"2008","journal-title":"Genome Res"},{"key":"2019121022375631100_dkz032-B17","first-page":"e000083.","article-title":"Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data","volume":"2","author":"Page","year":"2016","journal-title":"Microb Genom"},{"key":"2019121022375631100_dkz032-B18","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinformatics"},{"key":"2019121022375631100_dkz032-B19","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: rapid large-scale prokaryote pan genome analysis","volume":"31","author":"Page","year":"2015","journal-title":"Bioinformatics"},{"key":"2019121022375631100_dkz032-B20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mbs.2006.09.015","article-title":"Bayesian analysis of population structure based on linked molecular information","volume":"205","author":"Corander","year":"2007","journal-title":"Math Biosci"},{"key":"2019121022375631100_dkz032-B21","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":"2019121022375631100_dkz032-B22","first-page":"1396","article-title":"Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites","volume":"10","author":"Yang","year":"1993","journal-title":"Mol Biol Evol"},{"key":"2019121022375631100_dkz032-B23","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":"2019121022375631100_dkz032-B24","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1073\/pnas.95.6.3140","article-title":"Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms","volume":"95","author":"Maiden","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2019121022375631100_dkz032-B25","first-page":"e000102.","article-title":"Identification of Klebsiella capsule synthesis loci from whole genome data","volume":"2","author":"Wyres","year":"2016","journal-title":"Microb Genom"},{"key":"2019121022375631100_dkz032-B26","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1093\/jac\/dks261","article-title":"Identification of acquired antimicrobial resistance genes","volume":"67","author":"Zankari","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2019121022375631100_dkz032-B27","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1128\/AAC.02412-14","article-title":"In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing","volume":"58","author":"Carattoli","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2019121022375631100_dkz032-B28","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1146\/annurev.micro.59.030804.121325","article-title":"Multilocus sequence typing of bacteria","volume":"60","author":"Maiden","year":"2006","journal-title":"Annu Rev Microbiol"},{"key":"2019121022375631100_dkz032-B29","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1093\/nar\/gkr928","article-title":"Detection of recombination events in bacterial genomes from large population samples","volume":"40","author":"Marttinen","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2019121022375631100_dkz032-B30","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/jac\/dkx058","article-title":"Genomic landscape of extended-spectrum \u03b2-lactamase resistance in Escherichia coli from an urban African setting","volume":"72","author":"Musicha","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2019121022375631100_dkz032-B31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/jac\/dku340","article-title":"Differential contribution of AcrAB and OqxAB efflux pumps to multidrug resistance and virulence in Klebsiella pneumoniae","volume":"70","author":"Bialek-Davenet","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2019121022375631100_dkz032-B32","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1093\/bioinformatics\/bti553","article-title":"ACT: the Artemis comparison tool","volume":"21","author":"Carver","year":"2005","journal-title":"Bioinformatics"},{"key":"2019121022375631100_dkz032-B33","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1469-0691.2012.03805.x","article-title":"Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258","volume":"19","author":"Breurec","year":"2013","journal-title":"Clin Microbiol Infect"},{"key":"2019121022375631100_dkz032-B34","doi-asserted-by":"crossref","first-page":"466.","DOI":"10.1186\/1471-2334-13-466","article-title":"Predominance of Klebsiella pneumoniae ST14 carrying CTX-M-15 causing neonatal sepsis in Tanzania","volume":"13","author":"Mshana","year":"2013","journal-title":"BMC Infect Dis"},{"key":"2019121022375631100_dkz032-B35","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.7196\/SAMJ.2015.v105i12.9926","article-title":"Molecular characterisation and epidemiological investigation of an outbreak of blaOXA-181 carbapenemase-producing isolates of Klebsiella pneumoniae in South Africa","volume":"105","author":"Jacobson","year":"2015","journal-title":"S Afr Med J"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/74\/5\/1223\/28501323\/dkz032.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/74\/5\/1223\/28501323\/dkz032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T22:39:00Z","timestamp":1576017540000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/74\/5\/1223\/5333166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,18]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,2,18]]},"published-print":{"date-parts":[[2019,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkz032","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,5]]},"published":{"date-parts":[[2019,2,18]]}}}