In Vitro Activity of New β-Lactamase Inhibitor Combinations against bla_NDM, bla_KPC, and ESBL-Producing Enterobacteriales Uropathogens

Antibiotic resistance in uropathogens has increased substantially and severely affected treatment of urinary tract infections (UTIs). Lately, some new formulations, including meropenem/vaborbactam (MEV), ceftazidime/avibactam (CZA), and ceftolozane/tazobactam (C/T) have been introduced to treat infections caused by drug-resistant pathogens. This study was designed to screen Enterobacteriales isolates from UTI patients and to assess their antimicrobial resistance pattern, particularly against the mentioned (new) antibiotics. Phenotypic screening of extended-spectrum β-lactamase (ESBL) and carbapenem resistance was followed by inhibitor-based assays to detect K. pneumoniae carbapenemase (KPC), metallo-β-lactamase (MBL), and class D oxacillinases (OXA). Among 289 Enterobacteriales, E. coli (66.4%) was the most predominant pathogen, followed by K. pneumoniae (13.8%) and P. mirabilis (8.3%). The isolates showed higher resistance to penicillins and cephalosporins (70-87%) than to non-β-lactam antimicrobials (33.2-41.5%). NDM production was a common feature among carbapenem-resistant (CR) isolates, followed by KPC and OXA. ESBL producers were susceptible to the tested new antibiotics, but NDM-positive isolates appeared resistant to these combinations. KPC-producers showed resistance to only C/T. ESBLs and carbapenemase encoding genes were located on plasmids and most of the genes were successfully transferred to recipient cells. This study revealed that MEV and CZA had significant activity against ESBL and KPC producers.