부산대학교 도서관

AbstractObjective:We compared the activity of 8 novel β-lactam and tetracycline-derivative antibiotics against a cohort of clinical carbapenem-resistant Enterobacterales (CRE) isolates and investigated the incremental susceptibility benefit of the addition of an aminoglycoside, fluoroquinolone, or polymyxin to the β-lactam agents to assist with empiric antibiotic decision making.Methods:A collection of consecutive CRE clinical isolates from unique patients at 3 US hospitals (2016–2021) was assembled. Broth microdilution was performed to obtain antimicrobial susceptibility testing results. Mechanisms of carbapenem resistance were investigated through short-read and long-read whole-genome sequencing.Results:Of the 603 CRE isolates, 276 (46%) were carbapenemase producing and 327 (54%) were non–carbapenemase producing, respectively. The organisms most frequently identified were Klebsiella pneumoniae(38%), Enterobacter cloacaecomplex (26%), and Escherichia coli(16%). We obtained the following percent susceptibility to novel β-lactam agents: ceftazidime-avibactam (95%), meropenem-vaborbactam (92%), imipenem-relebactam (84%), and cefiderocol (92%). Aminoglycosides and the polymyxins provided greater incremental coverage as second agents, compared to fluoroquinolones. Amikacin and plazomicin exhibited the greatest additive value. Ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were active against 94% of the 220 KPC-producing isolates. Cefiderocol was active against 83% of the 29 NDM-producing isolates. Ceftazidime-avibactam had 100% activity against the 9 OXA-48-like–producing isolates. Tigecycline had the highest activity compared to other tetracyclines against KPC, NDM, or OXA-48-like–producing isolates.Conclusion:Selection among novel agents requires a nuanced understanding of the molecular epidemiology of CRE. This work provides insights into the comparative activity of novel agents and the additive value of a second antibiotic for empiric antibiotic decision making.