Genomic Epidemiology of Carbapenemase-Producing Enterobacterales at a Hospital System in Toronto, Ontario, Canada, 2007 to 2018

Abstract

At a hospital system (H1) in Ontario, Canada, we investigated whether whole-genome sequencing (WGS) altered initial epidemiological interpretation of carbapenemase-producing Enterobacterales (CPE) transmission. We included patients with CPE colonization/infection identified by population-based surveillance from October 2007 to August 2018 who received health care at H1 in the year before/after CPE detection. H1 reported epidemiological transmission clusters. We combined single nucleotide variant (SNV) analysis, plasmid characterization, and epidemiological data. Eighty-five patients were included. H1 identified 7 epidemiological transmission clusters, namely, A to G, involving 24/85 (28%) patients. SNV analysis confirmed transmission clusters C, D, and G and identified two additional cases belonging to cluster A. One was a travel-related case that was the likely index case (0 to 6 SNVs from other isolates); this case stayed on the same unit as the initially presumed index case 4 months prior to detection of the initially presumed index case on another unit. The second additional case occupied a room previously occupied by 5 cluster A cases. Plasmid sequence analysis excluded a case from cluster A and identified clusters E and F as possibly two parts of a single cluster. SNV analysis also identified a case without direct epidemiologic links that was 18 to 21 SNVs away from cluster B, suggesting possible undetected interhospital transmission. SNV and plasmid sequence analysis identified cases belonging to transmission clusters that conventional epidemiology missed and excluded other cases. Implementation of routine WGS to complement epidemiological transmission investigations has the potential to improve prevention and control of CPE in hospitals.

Keywords: beta-lactamases; carbapenem-resistant Enterobacteriaceae; disease transmission; genomic epidemiology; public health.

FIG 1

Carbapenemase/species of 91 carbapenemase-producing Enterobacterales (CPE) isolates belonging to patients who received health care at H1 from 2007 to 2018. a, One was a KPC/VIM coproducer, and one was a KPC/NDM coproducer.

FIG 2

Single nucleotide variant tree of all carbapenemase-producing Klebsiella pneumoniae (n = 38) (A) and Escherichia coli (n = 26) (B) isolates belonging to patients who received health care at H1 from 2007 to 2018. Transmission clusters are boxed and labeled.

FIG 3

Units that cluster A cases stayed on during their admissions to H1. Cases that stayed on unit A all stayed in unit A’s satellite room for ICU B.