In vitro activity of ceftazidime-avibactam, imipenem-relebactam, aztreonam-avibactam, and comparators toward carbapenem-resistant and hypervirulent Klebsiella pneumoniae isolates

Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) strains are increasingly reported, posing a significant threat to public health. Therefore, effective antimicrobial therapy is urgently needed. This study aimed to analyze the in vitro activity of ceftazidime-avibactam (CZA), imipenem-relebactam (IMR), and aztreonam-avibactam (AZA) toward CR-hvKP and carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates. Non-repetitive clinical CRKP and CR-hvKP strains were collected from Sichuan Provincial People's Hospital between August 2018 and June 2022. CR-hvKP strains were screened using string tests and polymerase chain reaction (PCR). The microbroth dilution method was used to evaluate in vitro antibacterial activity of CZA, IMR, and AZA toward CRKP and CR-hvKP stains. The molecular characteristics of CRKP and CR-hvKP strains were investigated using PCR amplification. The virulence features of CR-hvKP strains were investigated using serum resistance assays and a Galleria mellonella infection model. A total of 114 CRKP and 40 CR-hvKP strains were collected. The susceptibility rates of CRKP and CR-hvKP to tigecycline, colistin, and polymyxin B exceeded 89.5%. The susceptibility rates of CRKP and CR-hvKP to CZA were 64.0% and 77.5%, respectively; the susceptibility rates to IMR were 92.5% and 71.9%, respectively; and the susceptibility rates to AZA were 89.5% and 75.0%, respectively. Multilocus sequence typing and wzi-loci sequencing identified sequence type 11 KL64 as the predominant type in CRKP and CR-hvKP strains. Carbapenemase genes were dominated by blaKPC-2 and blaNDM-1. IMR and AZA may be promising therapeutic agents for the treatment of infections caused by CRKP and CR-hvKP isolates.