Dissemination of carbapenem-resistant Klebsiella pneumoniae complex in Portuguese hospitals. Klebsiella

Carbapenem-resistant Klebsiella pneumoniae complex (CR-KP) are a public health concern due to their high mortality, limited therapeutic options and challenging infection control strategies. In Portugal the rate of CR-KP has increased steeply, but the factors associated to this expansion are poorly explored. To address this question we compared, by phylogenetic and resistome analysis, the draft genomes of 200 CR-KP isolates collected in 2017-2019 from five hospitals in the Lisbon region, Portugal. We found that CR-KP belonged mainly to ST13 (29%), ST17 (15%), ST348 (13%), ST231 (12%) and ST147 (7%). Carbapenem resistance was conferred mostly by the presence of KPC-3 (74%) or OXA-181 (18%) determinants, which were present in multiple genetic backgrounds. KPC-3 positive isolates were associated with IncF plasmids (FIApBK30683) and OXA-181 were linked to the IncX plasmid family (IncX3). Almost all isolates were multidrug resistant harbouring resistance determinants to aminoglycosides, beta-lactams, trimethoprim, fosfomycin, quinolones and sulphonamides. In addition, 11% of isolates were resistant to colistin. Isolates colonizing patients, screened at hospital entrance, were highly related with those from infection, and most colonized patients (89%) reported a previous hospitalization. Moreover, among the 171 suggestive events of cross-dissemination identified by phylogenetic analysis of cgMLST data (Our results suggest that dissemination of CR-KP in five hospitals in the Lisbon region result from acquisition of carbapenemases in mobile genetic elements, influx of CR-KP into the hospitals by colonized ambulatory patients; and transmission of CR-KP within and between hospitals of the same regional network.Our data reinforces that the prudent use of carbapenems, the screening of patients at hospital entrance, and the reinforcement of infection control in hospitals will be needed to decrease the burden of CR-KP infection in Portugal.