Repeated local emergence of carbapenem-resistant in a single hospital ward.

We recently reported a dramatic increase in the prevalence of carbapenem-resistant infections in the intensive care unit (ICU) of a Vietnamese hospital. This upsurge was associated with a specific -positive clone that was identified by multilocus VNTR analysis. Here, we used whole-genome sequence analysis to dissect the emergence of carbapenem-resistant causing 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 of asymptomatic 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 of , and genes in multiple lineages. The majority of resistant isolates were -positive global clone GC2; fine-scale phylogenomic analysis revealed five distinct GC2 sublineages within the ICU that had evolved locally via independent chromosomal insertions of transposons. The increase in infections caused by carbapenem-resistant was 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 the isolated on the same ward, suggesting that diversification was largely facilitated via reassortment and sharing of genetic material within the localized population.