Abstract: To analyse the epidemiology and population structure of third-generation  cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016-2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016-2018).  Whole-genome sequencing was performed followed by multilocus sequencing  typing (MLST), core-genome MLST, and resistome and virulome analysis.  The admission prevalence of 3GCR K. pneumoniae complex isolates  during the 4-year study period was 0.8%, and 1.0 bloodstream infection  per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae.  cgMLST showed a polyclonal population of colonising and bloodstream  isolates, which was also reflected by MLST and virulome analysis.  CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and  29.7% of the colonising and 48.8% of the bloodstream isolates were  high-risk clones. The present study provides an insight into the  polyclonal 3GCR K. pneumoniae population in German hospitals.

Keywords: Klebsiella pneumoniae complex; bloodstream infections; carbapenem resistance; colonisation; third-generation cephalosporin resistance; typing.