Evaluation of Various Antimicrobial Susceptibility Tests for Novel β-Lactam/β-Lactamase Inhibitors against Carbapenem-Resistant Pathogens

Abstract

Background: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) have severely limited therapeutic options. Recently, Korea introduced novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations, such as ceftazidime-avibactam (CTZ-AVI, Zavicefta; Pfizer, Korea) and ceftolozane-tazobactam (CFZ-TAZ, Zerbaxa; MSD, Korea), increasing the demand for antimicrobial susceptibility testing. This study aims to evaluate various antimicrobial susceptibility tests for CTZ-AVI and CFZ-TAZ against carbapenem-resistant pathogens. Methods: A total of 132 carbapenem-resistant pathogens (76 CRE and 56 CRPA) were included. Antimicrobial susceptibility to CTZ-AVI and CFZ-TAZ was determined using the Etest (Liofilchem, USA) and compared with results from broth microdilution (Sensititre; Thermo Fisher Scientific, USA) or an automated system (VITEK 2 with Gram-negative extension panel; bioMérieux, France). Carbapenemase genotypes were identified using the Carba NP test (NG Biotech, France) or PCR sequencing. Results: Comparison of Etest and microdilution methods showed concordance rates of 100% for CTZ-AVI and 92.3% for CFZ-TAZ among 26 CRE isolates. For seven CRPA isolates, results were consistently accurate for both CTZ-AVI and CFZ-TAZ. When comparing Etest with automated methods, concordance rates were 98% for CTZ-AVI and 94% for CFZ-TAZ among 50 CRE isolates, and 100% for CTZ-AVI and 98% for CFZ-TAZ among 49 CRPA isolates. The susceptibility of most CRE isolates to CTZ-AVI and CFZ-TAZ could be predicted based on carbapenemase genotype. In CRPA, the presence of New Delhi metallo-β-lactamase and imipenemase appeared to contribute to resistance to both agents. Conclusions: All three methods are reliable for susceptibility testing of novel BL/BLI combinations against carbapenem-resistant pathogens.