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. 2023 May;44(5):762-767.
doi: 10.1017/ice.2022.161. Epub 2022 Jul 13.

Comparing the activity of novel antibiotic agents against carbapenem-resistant Enterobacterales clinical isolates

Pranita D Tamma  1 , Yehudit Bergman  2 , Emily B Jacobs  2 , Jae Hyoung Lee  1 , Shawna Lewis  2 , Sara E Cosgrove  3 , Patricia J Simner  2 ; Centers for Disease Control and Prevention Epicenters Program
Affiliations

Comparing the activity of novel antibiotic agents against carbapenem-resistant Enterobacterales clinical isolates

Pranita D Tamma et al. Infect Control Hosp Epidemiol. 2023 May.

Abstract

Objective: 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 cloacae complex (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.

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