Evolving resistance landscape in gram‐negative pathogens: An update on β‐lactam and β‐lactam‐inhibitor treatment combinations for carbapenem‐resistant organisms

Abstract

Antibiotic resistance has become a global threat as it is continuously growing due to the evolution of β‐lactamases diminishing the activity of classic β‐lactam (BL) antibiotics. Recent antibiotic discovery and development efforts have led to the availability of β‐lactamase inhibitors (BLIs) with activity against extended‐spectrum β‐lactamases as well as Klebsiella pneumoniae carbapenemase (KPC)‐producing carbapenem‐resistant organisms (CRO). Nevertheless, there is still a lack of drugs that target metallo‐β‐lactamases (MBL), which hydrolyze carbapenems efficiently, and oxacillinases (OXA) often present in carbapenem‐resistant Acinetobacter baumannii. This review aims to provide a snapshot of microbiology, pharmacology, and clinical data for currently available BL/BLI treatment options as well as agents in late stage development for CRO harboring various β‐lactamases including MBL and OXA‐enzymes.