Spread of ST11-O13/KL47 hypervirulent carbapenem-resistant Klebsiella pneumoniae isolates in China

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a serious threat to global public health. Hypervirulent CRKP (Hv-CRKP) can cause life-threatening infections, with significantly higher virulence and mortality compared to classical CRKP. CRKP strains were isolated from hospitalized patients in Shandong Province, China, 2018-2023. We performed whole-genome sequencing and bioinformatic analyses to determine the multilocus sequence typing (MLST), capsular typing, antimicrobial resistance genes, virulence factors, and plasmid incompatibility (Inc) typing of these strains. 81 CRKP strains were collected, with the major carbapenemase genes were blaNDM-1 (49.4%) and blaKPC-2 (42.0%), and the major MLST types of ST11 (40.7%), ST45 (27.2%), and ST37 (19.8%). ST11-KP was closely associated with blaKPC-2 (100%), and was primarily isolated from adults (93.9%), whereas ST45-KP and ST37-KP were closely linked to blaNDM-1 (100%) and frequently detected in neonates and infants. ST11-KP mostly harbored capsular type O13 (66.7%)/KL47 (63.6%), while the ST45-KP and ST37-KP majorly exhibited O2a (100%)/KL43 (95.5%) and O4 (93.8%)/KL15 (75%), respectively. There were three major CRKP clades: Clade I-ST11-blaKPC-2 (40.7%), Clade II-ST45-blaNDM-1 (27.2%), and Clade III-ST37-blaNDM-1 (18.5%). Notably, Clade I-ST11-blaKPC-2 strains harbored a set of virulence factors including rmpA2 (60.6%) and iucABCD/iutA (81.8%~97.0%), and mainly carried the IncFII/IncR plasmid (84.8%). Compared with non-Hv-CRKP, Hv-CRKP was associated with significantly higher levels of inflammatory factors including C-reactive protein ((34.6 ± 5.0) mg/L vs. (12.6 ± 2.9) mg/L, p < 0.001) and serum amyloid A ((153.8 ± 40.0) mg/L vs. (23.0 ± 7.6) mg/L, p < 0.001). ST11-O13/KL47 CRKP, characterized by high antimicrobial resistance and hypervirulence, has spread in China. Continuous surveillance of hypervirulent ST11-O13/KL47 CRKP is of importance.