Non-KPC Attributes of Newer -lactam/-lactamase Inhibitors, Part 1: Enterobacterales and Pseudomonas aeruginosa

Gram-negative antibiotic resistance continues to grow as a global problem due to the evolution and spread of beta-lactamases. The early beta-lactamase inhibitors (BLIs) are characterized by spectra limited to class A beta-lactamases and ineffective against carbapenemases and most extended spectrum beta-lactamases. In order to address this therapeutic need, newer BLIs were developed with the goal of treating carbapenemase producing, carbapenem resistant organisms (CRO), specifically targeting the Klebsiella pneumoniae carbapenemase (KPC). These BL/BLI combination drugs, avibactam/avibactam, meropenem/vaborbactam, and imipenem/relebactam, have proven to be indispensable tools in this effort. However, non-KPC mechanisms of resistance are rising in prevalence and increasingly challenging to treat. It is critical for clinicians to understand the unique spectra of these BL/BLIs with respect to non-KPC CRO. In Part 1of this 2-part series, we describe the non-KPC attributes of the newer BL/BLIs with a focus on utility against Enterobacterales and Pseudomonas aeruginosa. Ceftazidime/avibactam, meropenem/vaborbactam, and imipenem/cilastatin/relebactam were developed to treat KPC-producing Enterobacterales. These drugs, however, have clinical utility for non-KPC carbapenem-resistant organisms. In Part 1 of this 2-part series, we describe their non-KPC attributes with a focus on Enterobacterales and Pseudomonas aeruginosa.