Mechanisms of resistance to newer drugs against gram negative bacteria in enterobacterales.

BACKGROUND

The emergence of multidrug-resistant Gram-negative bacteria poses a significant threat to global health. This has prompted the development of novel antimicrobials and combinations with β-lactamase inhibitors.

OBJECTIVES

This review aims to shed light on the resistance mechanisms associated with new drugs against Enterobacterales.

SOURCES: We searched PubMed relevant English literature in up to 30 June 2025, as well as including articles known to the authors. We analysed Enterobacterales resistance mechanisms for diazabicyclooctanes, bicyclic boronates, cefepime/enmetazobactam, cefiderocol, and eravacycline.

CONTENT: The review summarises the main mechanisms of resistance to recently introduced ß-lactamase inhibitor families, including diazabicyclooctanes and bicyclic boronates, as well as other novel combinations or antimicrobials, such as cefiderocol and eravacycline.

IMPLICATIONS: Understanding how microorganisms develop resistance to new antimicrobials or combinations with inhibitors is essential for redesigning treatment strategies and for the design of future antibiotics.