Molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae: Risk factors and resistance mechanism of ceftazidime/avibactam in China

Wang, N.; Zhan, M.; Deng, L.; Li, H.; Peng, X.; Chang, J.; Hao, J.; Jia, N.; Li, B.; Lei, C.; Wang, T.; Liu, S.; Li, C.; Wang, B.; Zhang, W.

doi:10.1101/2024.11.27.625653

bioRxiv · 10.1101/2024.11.27.625653

Molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae: Risk factors and resistance mechanism of ceftazidime/avibactam in China

Wang, N.·Zhan, M.·Deng, L.·Li, H.·Peng, X.·Chang, J.·Hao, J.·Jia, N.·Li, B.·Lei, C.·Wang, T.·Liu, S.·Li, C.·Wang, B.·Zhang, W.

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Abstract

The high morbidity and mortality rates associated with carbapenem-resistant hypervirulent Klebsiella pneumoniae have become a global public health problem. We analyzed the whole genome sequence and epidemiological data of 81 carbapenem-resistant Klebsiella pneumoniae strains and conducted sensitivity experiments to explore the optimal concentration of carbapenem-resistant Klebsiella pneumoniae. We verified the resistance and virulence genes of carbapenem-resistant Klebsiella pneumoniae using polymerase chain reaction and compared virulence between carbapenem-resistant hypervirulent Klebsiella pneumoniae a ndcarbapenem-resistant-non-hypervirulent Klebsiella pneumoniae through Galleria mellonella assays.The prevalent types of multilocus sequence typing in our carbapenem-resistant Klebsiella pneumoniae strains were ST11 (69.14%, 56/81). ST11-K64-O1/O2v1 has become an epidemic type in our hospital, with drug-resistance genes dominated by blaKPC-2 (90.12%, 73/81). Ceftazidime/avibactam has better antibacterial effects on carbapenem-resistant Klebsiella pneumoniae, and its resistance is mainly mediated by a resistance plasmid containing the blaKPC-2 gene. 52 carbapenem-resistant hypervirulent Klebsiella pneumoniae strains carry the blaKPC-2, with a high detection rate of siderophore. Further research has shown that the genetic environment of the blaKPC-2 contains TnpR_Tn3 and ISKpn27 upstream and ISKpn6 insertion sequences downstream. Galleria mellonella revealed that the survival rate of carbapenem-resistant hypervirulent Klebsiella pneumoniae was lower than that of carbapenem-resistant-non-hypervirulent Klebsiella pneumoniae, and the survival rate of carbapenem-resistant hypervirulent Klebsiella pneumoniae-K64 was lower than that of carbapenem-resistant hypervirulent Klebsiella pneumoniae-K47.The spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae strains is alarming, necessitating molecular monitoring of hypervirulent strains and strengthening the nosocomial infection prevention and control measures. Antibiotics should be used reasonably based on patients infection status and local epidemiological data. ImportanceCarbapenem-resistant Klebsiella pneumonia is a global public health concern. We conducted a molecular epidemiological analysis of 81 carbapenem-resistant hypervirulent Klebsiella pneumoniae strains from our hospital and explored the resistance mechanism of ceftazidime/avibactam. We identified the blaKPC-2 gene to be primarily responsible for carbapenem resistance in our hospital, and ST11-K64 was the dominant clone. A high-risk clone, ST307-K102, was detected, necessitating strengthened surveillance to prevent its spread. This studys findings contribute to the optimization of antimicrobial management and indicate that genomic research can assist with the tracking of hospital infection outbreaks and the improvement of infection-control measures.

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Wang, N., Zhan, M., Deng, L., Li, H., Peng, X., Chang, J., Hao, J., Jia, N., Li, B., Lei, C., Wang, T., Liu, S., Li, C., Wang, B., Zhang, W.. 2024-11-27. Molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae: Risk factors and resistance mechanism of ceftazidime/avibactam in China. https://doi.org/10.1101/2024.11.27.625653

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