A nationwide genomic study of clinical Klebsiella pneumoniae in Norway 2001-2015: Introduction and spread of ESBL facilitated by CG15 and CG307

Abstract

SynopsisO_ST_ABSObjectiveC_ST_ABSWe have used the nationwide Norwegian surveillance program on resistant microbes in humans (NORM) to address longitudinal changes in the population structure K. pneumoniae isolates during 2001-15, encompassing the emergence and spread of ESBL-producing Enterobacterales (ESBL-E) in Norway. Material and methodsAmong blood (n= 6124) and urinary tract (n=5496) surveillance isolates from 2001-15, we used Illumina technology to whole genome sequence 201 ESBL-producing isolates from blood (n=130) and urine (n=71), and 667 non-ESBL isolates from blood. Complete genomes for four isolates were resolved with Oxford Nanopore sequencing. ResultsIn a highly diverse collection, Klebsiella variicola ssp. variicola caused a quarter of Klebsiella pneumoniae species complex bacteraemias. ESBL-production was limited to K. pneumoniae sensu stricto (98.5 %). A diverse ESBL population of 57 clonal groups (CGs) were dominated by multidrug resistant CG307 (17%), CG15 (12%), CG70 (6%), CG258 (5%) and CG45 (5%) carrying blaCTX-M-15. Yersiniabactin was significantly more common in ESBL-positive (37.8%) compared to non-ESBL K. pneumoniae sensu stricto isolates (12.7%), indicating convergence of virulence and resistance determinants Moreover, we found a significant lower prevalence of yersinabactin (3.0 %, 37.8 % and 17.3 %), IncFIB (58.7 %, 87.9 % and 79.4 %) and IncFII plasmid replicons (40.5 %, 82.8 % and 54.2%) in K. variicola ssp. variicola compared to ESBL- and non-ESBL K. pneumoniae sensu stricto, respectively. ConclusionThe increase in Norwegian KpSC ESBLs during 2010-15 was driven by blaCTX-M-15 carrying CG307 and CG15. K. variicola ssp. variicola was a frequent cause of invasive KpSC infection, but rarely carried ESBL.