In vitro activity of imipenem/relebactam and ceftazidime/avibactam against carbapenem-resistant Klebsiella pneumoniae from blood cultures in a University hospital in Serbia

Abstract The study aimed to investigate prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) blood culture isolates and their susceptibility to two new antibiotics, imipenem/relebactam and ceftazidime/avibactam. Out of 765 isolates recovered from blood cultures in a tertiary care hospital in Serbia between 2020 and 2023, 143 non-repetitive K. pneumoniae strains were included in this study. Minimum inhibitory concentration (MIC) values of the examined antimicrobial drugs was determined by VITEK 2 system, MIC test strip (imipenem/relebactam and ceftazidime/avibactam), and broth microdilution method (tigecycline and colistin). Carbapenemase-encoding genes ( bla KPC , bla OXA-48-like , bla NDM , bla VIM , bla IMP ) were detected using a multiplex-PCR assay, the BioFire-Blood Culture Identification 2-panel. This closed molecular assay is designed for the BioFire® FilmArray® system, enabling automated sample preparation, amplification, detection, and analysis (bioMérieux, France). Results revealed that K. pneumoniae was the most common isolate from blood cultures in 2022. The prevalence of K. pneumoniae was about 11.6% in 2020 and 2021, while in 2022 it raised to over 30%. Also, the frequency of CRKP increased from 11.76% in 2020, through 15.29% in 2021 to 72.94% in 2022. The majority of CRKP carried bla OXA-48-like (60.0%), followed by bla KPC (16.47%), and bla NDM (8.24%) genes, while 14.12% harboured both bla OXA-48-like and bla NDM genes. Only 25.88% of CRKP isolates were resistant to ceftazidime/avibactam, while 51.76% were resistant to imipenem/relebactam and colistin. The rapid spread of CRKP is particularly concerning because therapeutic options are limited to a few antibiotics. While imipenem/relebactam and colistin showed similar antimicrobial activity against CRKP clinical isolates, ceftazidime/avibactam proved to be the most effective antibiotic.