Genomic inference of sites of transmission during regional spread of bla

The frequent movement of colonized and infected patients between healthcare facilities makes it challenging to discern where individual patients acquire healthcare-associated pathogens, and in turn, identify facilities making the greatest contributions to regional spread. Here, we implement an approach using genomic and healthcare exposure histories from passively collected regional isolates to identify the putative facility source for each new isolate by analyzing shared healthcare exposures with earlier case patients whose isolates were phylogenetically closest. As a proof of principle, we apply this approach to data collected by a state health department during a suspected regional outbreak of carbapenem-resistant Klebsiella pneumoniae involving 72 patients exposed to 47 healthcare facilities in Michigan from October 2019 to May 2022. Examination of transmission linkages supported a sustained role played by a single focal facility, with other facilities inferred as sources of smaller numbers of cases. Importantly, in several instances, facilities were implicated as sites of transmission prior to cases being detected there, based on overlapping exposures among genomically linked cases. The ability to infer facility sources of transmission using passively collected regional isolates supports the potential for real-time genome-informed surveillance to enable timely targeting of interventions to interrupt regional spread of healthcare-associated pathogens.