In vitro Activity of Cefiderocol and Ceftazidime-Avibactam, Against Carbapenemase-Producing Enterobacterales

Background: Carbapenemase production is an issue of significant clinical and public health concern, because of the shortage of effective antimicrobial agents available for treatment. Here, we present antimicrobial susceptibili-ty data of ceftazidime-avibactam, cefiderocol, and other clinically relevant antibiotics for carbapenemase-produc-ing Enterobacterales bloodstream isolates, in accordance with European Committee on Antimicrobial Susceptibili-ty Testing (EUCAST) guidelines. Methods: A total of 133 carbapenemase producing Enterobacterales bloodstream isolates from May 2010 to Sep-tember 2018 were included in the study. Species were identified using matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (Bruker Daltonics, Germany). The presence of the blaKPC, blaNDM, blaOXA-48, blaVIM, and blaIMP carbapenemase genes were investigated by BD Max CRE assay (Becton Dickinson, USA) and in-house PCR. Antimicrobial susceptibility testing was performed by the BD Phoenix automated system (Becton Dickinson, USA), except cefiderocol and colistin. Cefiderocol and colistin susceptibility was determined by disk diffusion and broth microdilution method, respectively. Results: Except for cefiderocol and ceftazidime-avibactam, the percentage of susceptible isolates did not exceed 90% for any of the antibiotics tested. Although none of the isolates were resistant to cefiderocol, the ceftazidime-avibactam resistance rate was 9.8%. All of the ceftazidime-avibactam resistant strains were NDM (New Delhi metallo-beta-lactamases) producers. Among the other clinically relevant antibiotics tested, only amikacin, colistin, tigecycline, and fosfomycin susceptibility rates exceeded 50%. Of the 133 isolates 22.6% were resistant to colistin which is the preferred antibiotic with a second active agent for infections caused by metallo-beta-lactamase pro-ducing Enterobacterales in Turkey. Conclusions: In our study, resistance to ceftazidime-avibactam was detected only in metallo-beta-lactamase pro-ducing Enterobacterales isolates, while cefiderocol was found to be effective against all strains. It is important to monitor regional antimicrobial susceptibility data, as the emergence of antimicrobial resistant phenotypes is di-rectly linked to the use of any given antimicrobial agent.