title: Repeated local emergence of carbapenem-resistantAcinetobacter baumanniiin a single hospital ward.
abstract: We recently reported a dramatic increase in the prevalence of carbapenem-resistantAcinetobacter baumanniiinfections in the intensive care unit (ICU) of a Vietnamese hospital. This upsurge was associated with a specificoxa23-positive clone that was identified by multilocus VNTR analysis. Here, we used whole-genome sequence analysis to dissect the emergence of carbapenem-resistantA. baumanniicausing ventilator-associated pneumonia (VAP) in the ICU during 2009-2012. To provide historical context and distinguish microevolution from strain introduction, we compared these genomes with those ofA. baumanniiasymptomatic carriage and VAP isolates from this same ICU collected during 2003-2007. We identified diverse lineages co-circulating over many years. Carbapenem resistance was associated with the presence ofoxa23,oxa40, oxa58andndm1genes in multiple lineages. The majority of resistant isolates wereoxa23-positive global clone GC2; fine-scale phylogenomic analysis revealed five distinct GC2 sublineages within the ICU that had evolved locally via independent chromosomal insertions ofoxa23transposons. The increase in infections caused by carbapenem-resistantA. baumanniiwas associated with transposon-mediated transmission of a carbapenemase gene, rather than clonal expansion or spread of a carbapenemase-harbouring plasmid. Additionally, we found evidence of homologous recombination creating diversity within the local GC2 population, including several events resulting in replacement of the capsule locus. We identified likely donors of the imported capsule locus sequences amongst theA. baumanniiisolated on the same ward, suggesting that diversification was largely facilitated via reassortment and sharing of genetic material within the localizedA. baumanniipopulation.
authors.affiliation: 2​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.|1​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Schultz
authors.affiliation: 3​The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Duy
authors.initials: D
authors.lastname: Pham Thanh
authors.affiliation: 3​The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Nhu
authors.initials: N
authors.lastname: Tran Do Hoan
authors.affiliation: 1​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.|2​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Wick
authors.affiliation: 1​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.|2​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Ingle
authors.affiliation: 1​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.|2​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Hawkey
authors.affiliation: 1​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.|2​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Edwards
authors.affiliation: 4​School of Molecular Bioscience, University of Sydney, New South Wales, Australia.|5​School of Biomedical Science, Queensland University of Technology, Queensland, Australia.
authors.forename: Johanna J
authors.initials: JJ
authors.lastname: Kenyon
authors.affiliation: 3​The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|6​Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, London, UK.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Phu Huong Lan
authors.affiliation: 3​The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: James I
authors.initials: JI
authors.lastname: Campbell
authors.affiliation: 3​The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Guy
authors.initials: G
authors.lastname: Thwaites
authors.affiliation: 3​The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|6​Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, London, UK.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Thi Khanh Nhu
authors.affiliation: 4​School of Molecular Bioscience, University of Sydney, New South Wales, Australia.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Hall
authors.affiliation: 7​Department of Genetics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fournier-Level
authors.affiliation: 3​The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|6​Centre for Tropical Medicine, Nuffield Department of Medicine, Oxford University, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: 1​Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.|2​Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
mesh_terms: D000151:Acinetobacter Infections / Q000453:epidemiology* / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D015780:Carbapenems; D024881:Drug Resistance, Bacterial / Q000235:genetics; D019143:Evolution, Molecular; D005798:Genes, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D010802:Phylogeny; D053717:Pneumonia, Ventilator-Associated / Q000382:microbiology*; D011995:Recombination, Genetic; D014744:Vietnam / Q000453:epidemiology; D000073336:Whole Genome Sequencing
chemical_list: D015780:Carbapenems
keywords: capsule switching; hospital acquired infection; imipenem resistance; local evolution; molecular epidemiology; phylogenomic analysis