Risk Factors Associated with Carbapenemase-Producing Enterobacterales (CPE) Positivity in the Hospital Wastewater Environment

Background: Hospital wastewater is an increasingly recognized reservoir for resistant Gram-negative organisms. Factors involved in establishment and persistence of Klebsiella pneumoniae carbapenemase-producing organisms (KPCO) in hospital wastewater plumbing are unclear. Methods: This study was conducted at a hospital with endemic KPCO linked to wastewater reservoirs and robust patient perirectal screening for silent KPCO carriage. Over five months, both rooms occupied and not occupied by KPCO-positive patients were sampled at three wastewater sites. Risk factors for KPCO positivity were assessed using logistic regression. Whole genome sequencing identified environmental seeding by KPCO-positive patients. Findings: 219/475 (46%) room sampling events were KPCO-positive in at least one wastewater site (sink drain, P-trap, or toilet/hopper). KPCO-positive patient exposure was associated with increased risk of environmental positivity for the room and toilet/hopper. Previous positivity and intensive care unit room type were consistently associated with increased risk. Tube feeds were associated with increased risk for the drain, while exposure to patients with Clostridioides difficile was associated with decreased risk. Urinary catheter exposure was associated with increased risk of P-trap positivity. P-trap heaters reduced risk of P-trap and sink drain positivity. Six of 99 room occupations by 40 KPCO-positive patients resulted in genomically-linked environmental seeding. Interpretation: KPCO-positive patients seed the environment in 6-8% of opportunities; once positive for KPCO, wastewater sites are at greater risk of being positive subsequently. Use of sinks for activities other than hand hygiene may increase risk; frequent flushing may be protective. Preventing establishment of drug-resistant Enterobacterales in hospital plumbing will require multi-faceted approaches.Funding Statement: This study was funded by the Center for Disease Control and Prevention (grant BAA 200-2017- 96194). SCP was supported by the National Institutes of Health (NIH) Infectious Diseases Training Grant (no. 5T32AI07046-42). DC, TEAP and ASW are supported by the National Institutes of Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (PHE) [HPRU-2012-10041] and the NIHR Oxford Biomedical Research Centre. TEAP and ASW are NIHR Senior Investigators. Declaration of Interests: AJM participated in the Tango II trial with meropenem/vaborbactam and was a former consultant to the Medisans Company. The remaining authors have nothing to declare.Ethics Approval Statement: Data was collected from the infection prevention and control database established under the University of Virginia Institutional Review Board protocol 18393. Data analysis and patient chart review was done under protocols 18776 and 13558.