Filling the Gaps: A Review and Update on Beta-Lactamase Inhibitor Combinations

Abstract Purpose of Review Gram-negative antimicrobial resistance continues to pose a growing threat, particularly among high-priority pathogens such as difficult-to-treat Pseudomonas aeruginosa , carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Enterobacterales (CRE). The rise in resistance has spurred the development of novel beta-lactam/beta-lactamase inhibitor (BL/BLI) combinations. However, the pace of innovation has lagged behind the rapid emergence of resistance, especially for CRAB and metallo-beta-lactamase (MBL)-producing Enterobacterales, organisms for which effective treatment options have been historically limited. This review outlines the pharmacologic characteristics, activity, and clinical efficacy data for newly approved BL/BLIs Recent Findings The FDA has recently approved Xacduro (sulbactam/durlobactam), Exblifep (cefepime/enmetazobactam), and Emblaveo (aztreonam/avibactam). Additionally, promising pipeline agents such as cefepime/taniborbactam, cefepime/zidebactam, and imipenem/cilastatin/funobactam warrant discussion. These agents offer significant potential to fill longstanding therapeutic gaps. Summary As resistance mechanisms evolve and therapeutic challenges persist, development of novel BL/BLIs will play an increasingly critical role in the management of multidrug-resistant gram-negative infections.