Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of bla KPC-carbapenemase-producing Enterobacterales in a hospital setting

N Stoesser; R George; Z Aiken; H T T Phan; S Lipworth; T P Quan; A J Mathers; N De Maio; A C Seale; D W Eyre; A Vaughan; J Swann; T E A Peto; D W Crook; J Cawthorne; A Dodgson; A S Walker; TRACE Investigators Group

doi:10.1093/jacamr/dlae140

Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of bla _KPC-carbapenemase-producing Enterobacterales in a hospital setting

JAC Antimicrob Resist. 2024 Sep 3;6(5):dlae140. doi: 10.1093/jacamr/dlae140. eCollection 2024 Oct.

Authors

N Stoesser^{1

2

3}, R George⁴, Z Aiken⁴, H T T Phan⁵, S Lipworth¹, T P Quan^{1

2}, A J Mathers⁶, N De Maio⁷, A C Seale⁸, D W Eyre^{1

2

3}, A Vaughan¹, J Swann¹, T E A Peto^{1

3}, D W Crook^{1

2

3}, J Cawthorne⁴, A Dodgson⁴, A S Walker^{1

2

3}; TRACE Investigators Group

Collaborators

Affiliations

¹ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
² NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, Nuffield Department of Medicine, Oxford, UK.
³ NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK.
⁴ Department of Microbiology, Manchester University NHS Foundation Trust, Manchester, UK.
⁵ Academic Unit of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
⁶ Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁷ Goldman Group, EMBL-European Bioinformatics Institute, Cambridge, UK.
⁸ Warwick Medical School - Health Sciences, University of Warwick, Coventry, UK.

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 bla_KPC-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 < 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 bla_KPC 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.

Grants and funding

WT_/Wellcome Trust/United Kingdom