Antibacterial efficacy of cefoperazone/sulbactam in combination with various antimicrobials against carbapenem-resistant Klebsiella pneumoniae

Abstract Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the major Gram-negative bacteria in human infections, which can cause pneumonia, sepsis, meningitis, and abscess. However, the current therapy for CRKP infection is polymyxin and tigecycline. The aim of this study is to analyze the in vitro antibacterial effects of cefoperazone/sulbactam (SCF) combined with ceftazidime (CAZ), imipenem/cilastatin (IMI), and meropenem (MEM) against CRKP harbouring different antibiotic resistance genes. In this study, fifteen clinical isolates of CRKP from January to December 2023 were taken from our hospital for bacterial identification and confirmation of carbapenemase genotypes, and the minimum inhibitory concentration (MIC) of SCF, CAZ, IMI, and MEM were determined by broth microdilution method. The results of combined drug sensitivity test were determined by checkerboard method and characterized with fractional inhibitory concentration (FIC). The combined antibacterial activity was determined by time-kill curve. The results showed that among the 15 CRKP strains, 9 carried bla KPC gene, 3 carried bla NDM gene and 3 carried bla OXA-48-like gene. The MIC values determined by broth microdilution method showed better sensitivity of KPC-producing CRKP to four antimicrobial drugs including SCF. However, bla NDM as well as bla OXA-48-like genotypes showed strong resistance to all four antimicrobial drugs. The FIC values of SCF combined with CAZ, IMI and MEM showed that all tested antibacterial agents had the best effect on KPC-producing CRKP, and had no obvious additive effect on other CRKP. The results of time-kill curve showed that SCF combined with IMI had good antibacterial effect. This study found that SCF combined with IMI has a synergistic antibacterial effect on KPC producing carbapenem-resistant K. pneumoniae , which could provide reference for clinical practice.