Risk factors for Klebsiella pneumoniae carbapenemase (KPC) gene acquisition and clinical outcomes across multiple bacterial species.

INTRODUCTION: Risk factors for carbapenemase-producing Enterobacterales (CPE) acquisition/infection and associated clinical outcomes have been evaluated in the context of clonal, species-specific outbreaks. Equivalent analyses for complex, multi-species outbreaks, which are increasingly common, are lacking. METHODS: Between December 2010 and January 2017, a case-control study of Klebsiella pneumoniae carbapenemase (KPC)-producing organism (KPCO) acquisition was undertaken using electronic health records from inpatients in a US academic medical centre and long-term acute care hospital (LTACH) with ongoing multi-species KPCO transmission despite a robust CPE screening programme. Cases had a first KPCO-positive culture >48 h after admission, and included colonizations and infections (defined by clinical records). Controls had at least two negative perirectal screens and no positive cultures. Risk factors for KPCO acquisition, first infection following acquisition, and 14-day mortality following each episode of infection were identified using multi-variable logistic regression. RESULTS: In 303 cases (89 with at least one infection) and 5929 controls, risk factors for KPCO acquisition included: longer inpatient stay, transfusion, complex thoracic pathology, mechanical ventilation, dialysis, and exposure to carbapenems and β-lactam/β-lactamase inhibitors. Exposure to other KPCO-colonized patients was only a risk factor for acquisition in a single unit, suggesting that direct patient-to-patient transmission did not play a major role. There were 15 species of KPCO; 61 (20%) cases were colonized/infected with more than one species. Fourteen-day mortality following non-urinary KPCO infection was 20% (20/97 episodes) and was associated with failure to achieve source control. CONCLUSIONS: Healthcare exposures, antimicrobials and invasive procedures increased the risk of KPCO colonization/infection, suggesting potential targets for infection control interventions in multi-species outbreaks. Evidence for patient-to-patient transmission was limited.