In vitro activity of ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam and cefiderocol against carbapenemase-producing Enterobacterales from clinical isolates in a tertiary healthcare centre in Serbia

Abstract

The aim of the study was to detect carbapenemase genes in clinically significant carbapenemase-producing Enterobacterales (CPE) and assess their susceptibility to newer antibiotics: ceftazidime-avibactam, ceftolozane-tazobactam, imipenem/relebactam, meropenem-vaborbactam, and cefiderocol. From January 2018 to February 2019, 866 Gram-negative bacilli were isolated, and among them 775 were identified as Enterobacterales. Out of the tested Enterobacterales, phenotypic testing revealed potential carbapenemase production in 95 isolates. A total of 56 clinically significant isolates were selected for molecular analysis. Species identification and antimicrobial susceptibility for conventional antibiotics was done using the VITEK 2 system, while carbapenemase genes were detected via Multiplex PCR. Antimicrobial susceptibility for newer antibiotics was determined by the MIC test strips. The predominant genotypes were blaNDM (39.3%) and blaOXA-48 (37.5%), with Klebsiella pneumoniae as the most prevalent producer (71.42%). Cefiderocol showed 100% effectiveness against all isolates. Ceftazidime-avibactam demonstrated high activity against OXA-48 and KPC producers (95.5% and 100% susceptibility, respectively). Meropenem-vaborbactam significantly improved susceptibility among NDM-. OXA-48/NDM-, and OXA-48-producing isolates, and imipenem-relebactam among OXA-48 CPE. Statistically significant differences in susceptibility were observed for OXA-48 and NDM producers to imipenem (P < 0.01), imipenem-relebactam (P < 0.001), and ceftazidime-avibactam (P < 0.001). In conclusion, the high prevalence of NDM-producing CPE strains significantly reduces the effectiveness of newer antibiotics. Cefiderocol appears to be the most effective therapeutic option, particularly for NDM producers, where it often represents the only viable treatment choice, while ceftazidime-avibactam is an effective option for OXA-48 producers. Statistically significant differences in susceptibility highlight the need for early detection of carbapenemases in clinical practice.

Keywords: antimicrobial resistance; carbapenem resistance; carbapenemase-producing Enterobacterales (CPE); cefiderocol; ceftazidime-avibactam; ceftolozane-tazobactam; imipenem-relebactam; meropenem-vaborbactam.