Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of <i>bla</i> KPC-carbapenemase-producing Enterobacterales in a hospital setting
Nicole Stoesser, Ryan George, Zoie Aiken, Hang Phan, Samuel Lipworth, T. Phuong Quan, Amy J. Mathers, Nicola De Maio, Anna C. Seale, David W. Eyre, Alison Vaughan, Jeremy Swann, Tim Peto, Derrick W. Crook, Julie Cawthorne, Andrew Dodgson, Andrew Walker, TRACE Investigators Group, Zoie Aiken, Oluwafemi Akinremi, Aiysha Ali, Julie Cawthorne, Paul Cleary, Derrick W. Crook, Valérie Decraene, Andrew Dodgson, Michel Doumith, Matthew J. Ellington, Ryan George, John Grimshaw, Malcolm Guiver, Robert L. Hill, Katie L. Hopkins, Rachel Jones, Cheryl Lenney, Amy J. Mathers, Ashley McEwan, Ginny Moore, Andrew Mumford, Mark Neilson, Sarah Neilson, Tim E A Peto, Hang Phan, Mark Regan, Anna C. Seale, Nicole Stoesser, Jay Turner-Gardner, Vicky Watts, A Sarah Walker, Jimmy Walker, William Welfare, Neil Woodford, David Wyllie
Abstract
Abstract Background Healthcare-associated wastewater and asymptomatic patient reservoirs colonized by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination, but the characteristics and dynamics of this remain unclear. Methods We systematically sampled wastewater sites (n = 4488 samples; 349 sites) and patients (n = 1247) across six wards over 6–12 months to understand blaKPC-associated CPE (KPC-E) diversity within these reservoirs and transmission in a healthcare setting. Up to five KPC-E-positive isolates per sample were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based approaches were used to characterize antimicrobial resistance genes, insertion sequences (ISs) and Tn4401 types/target site sequences. The accessory genome was evaluated in some of the largest clusters, and those crossing reservoirs. Results Wastewater site KPC-E-positivity was substantial [101/349 sites (28.9%); 228/5601 (4.1%) patients cultured]. Thirteen KPC-E species and 109 strains were identified using genomics, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured one or more strains. Most diversity was explained by the individual niche, suggesting localized factors are important in selection and spread. Tn4401 + flanking target site sequence diversity was greater in wastewater sites (P &lt; 0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath- and sluice/mop-associated sites were more likely to be KPC-E-positive (adjusted OR = 2.69; 95% CI: 1.44–5.01; P = 0.0019; and adjusted OR = 2.60; 95% CI: 1.04–6.52; P = 0.0410, respectively). Different strains had different blaKPC dissemination dynamics. Conclusions We identified substantial and diverse KPC-E colonization of wastewater sites and patients in this hospital setting. Reservoir and niche-specific factors (e.g. microbial interactions, selection pressures), and different strains and mobile genetic elements likely affect transmission dynamics. This should be considered in surveillance and control strategies.