Genomic Insights into the expansion of Carbapenem-Resistant Klebsiella pneumoniae within Portuguese Hospitals.

Carbapenem-resistant Klebsiella pneumoniae complex (CR-KP) are a public health concern, causing infections with a high mortality rate, limited therapeutic options and challenging infection control strategies. In Portugal CR-KP rate 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 KPC-3 (74%) or OXA-181 (18%) presence, which were associated with IncF/IncN and IncX plasmids, respectively. 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. Colonizing and infection isolates were highly related and most colonized patients (89%) reported a previous hospitalization. Moreover, among the 171 events of cross-dissemination identified, by cgMLST data analysis (<5 alleles), 41 occurred between different hospitals and 130 within the same hospital. Our results suggest that CR-KP dissemination 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. Our data reinforces that the prudent use of carbapenems, patients screening at hospital entrance, and improvement of infection control will be needed to decrease the burden of CR-KP infection in Portugal.