Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae at a Single Institution: Insights into Endemicity from Whole-Genome Sequencing

<jats:title>ABSTRACT</jats:title><jats:p>The global emergence of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Klebsiella pneumoniae</jats:named-content>carbapenemase-producing<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">K. pneumoniae</jats:named-content>(KPC-<jats:italic>Kp</jats:italic>) multilocus sequence type ST258 is widely recognized. Less is known about the molecular and epidemiological details of non-ST258<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">K. pneumoniae</jats:named-content>in the setting of an outbreak mediated by an endemic plasmid. We describe the interplay of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>plasmids and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">K. pneumoniae</jats:named-content>strains and their relationship to the location of acquisition in a U.S. health care institution. Whole-genome sequencing (WGS) analysis was applied to KPC-<jats:italic>Kp</jats:italic>clinical isolates collected from a single institution over 5 years following the introduction of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>in August 2007, as well as two plasmid transformants. KPC-<jats:italic>Kp</jats:italic>from 37 patients yielded 16 distinct sequence types (STs). Two novel conjugative<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>plasmids (pKPC_UVA01 and pKPC_UVA02), carried by the hospital index case, accounted for the presence of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>in 21/37 (57%) subsequent cases. Thirteen (35%) isolates represented an emergent lineage, ST941, which contained pKPC_UVA01 in 5/13 (38%) and pKPC_UVA02 in 6/13 (46%) cases. Seven (19%) isolates were the epidemic KPC-<jats:italic>Kp</jats:italic>strain, ST258, mostly imported from elsewhere and not carrying pKPC_UVA01 or pKPC_UVA02. Using WGS-based analysis of clinical isolates and plasmid transformants, we demonstrate the unexpected dispersal of<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>to many non-ST258 lineages in a hospital through spread of at least two novel<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>plasmids. In contrast, ST258 KPC-<jats:italic>Kp</jats:italic>was imported into the institution on numerous occasions, with other<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>plasmid vectors and without sustained transmission. Instead, a newly recognized KPC-<jats:italic>Kp</jats:italic>strain, ST941, became associated with both novel<jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>plasmids and spread locally, making it a future candidate for clinical persistence and dissemination.</jats:p>