Molecular epidemiology of carbapenem-resistant hypervirulentKlebsiella pneumoniae: Risk factors and resistance mechanism of ceftazidime/avibactam in China
Authors: Wang Na , Zhan Minghua , Deng Lexiu , Li Huiying , Peng Xiaocui , Chang Jianliang , Hao Jiatong , Jia Na , Li Baoliang , Lei Chunmei , Wang Teng , Liu Shuting , Li Caiqing , Wang Bu , Zhang Wei 
Published: November 2024

The high morbidity and mortality rates associated with carbapenem-resistant hypervirulentKlebsiella pneumoniaehave become a global public health problem. We analyzed the whole genome sequence and epidemiological data of 81 carbapenem-resistantKlebsiella pneumoniaestrains and conducted sensitivity experiments to explore the optimal concentration of carbapenem-resistantKlebsiella pneumoniae. We verified the resistance and virulence genes of carbapenem-resistantKlebsiella pneumoniaeusing polymerase chain reaction and compared virulence between carbapenem-resistant hypervirulentKlebsiella pneumoniaea ndcarbapenem-resistant-non-hypervirulentKlebsiella pneumoniaethroughGalleria mellonellaassays.The prevalent types of multilocus sequence typing in our carbapenem-resistantKlebsiella pneumoniaestrains 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-resistantKlebsiella pneumoniae, and its resistance is mainly mediated by a resistance plasmid containing the blaKPC-2gene. 52 carbapenem-resistant hypervirulentKlebsiella pneumoniaestrains carry the blaKPC-2, with a high detection rate of siderophore. Further research has shown that the genetic environment of the blaKPC-2contains TnpR_Tn3 and ISKpn27 upstream and ISKpn6 insertion sequences downstream.Galleria mellonellarevealed that the survival rate of carbapenem-resistant hypervirulentKlebsiella pneumoniaewas lower than that of carbapenem-resistant-non-hypervirulentKlebsiella pneumoniae, and the survival rate of carbapenem-resistant hypervirulentKlebsiella pneumoniae-K64 was lower than that of carbapenem-resistant hypervirulentKlebsiella pneumoniae-K47.The spread of carbapenem-resistant hypervirulentKlebsiella pneumoniaestrains 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.

Importance

Carbapenem-resistantKlebsiella pneumoniais a global public health concern. We conducted a molecular epidemiological analysis of 81 carbapenem-resistant hypervirulentKlebsiella pneumoniaestrains from our hospital and explored the resistance mechanism of ceftazidime/avibactam. We identified the blaKPC-2gene 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 study’s 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.