Carbapenemases: epidemiology, detection and management in a changing global landscape

Abstract Carbapenemase-producing Gram-negative bacteria are a growing threat to last-line beta-lactam (BL) therapy and are now established across Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii. Since the first reports in the 1980s, carbapenemase genes have disseminated internationally through plasmids, transposons and integrons and have become embedded in high-risk clones, with contemporary epidemiology dominated by Klebsiella pneumoniae carbapenemases (KPC), New Delhi metallo-beta-lactamase, Verona integron-encoded, imipenemase and oxacillinase (OXA)-type enzymes. The past decade has been marked by spread beyond hospitals, rising metallo-beta-lactamase (MBL) prevalence, and convergence of resistance with hypervirulence in some lineages. This Review summarizes carbapenemase classification, genetic contexts and epidemic clones. It describes regional distribution patterns alongside One Health drivers linking healthcare, community, animal and environmental reservoirs. We outline a pragmatic diagnostic framework spanning screening, confirmatory phenotypic assays, rapid lateral flow and molecular platforms, and whole genome sequencing for surveillance and outbreak investigation, emphasizing the clinical value of early mechanism identification for both infection control and targeted therapy. Treatment is reviewed in a mechanism-directed manner: newer BL/beta-lactamase inhibitor combinations are central for serine carbapenemases (including KPC and many OXA-48-like producers), whereas MBL producers require alternative strategies such as aztreonam-based combinations or cefiderocol. Options remain limited for carbapenemase-producing P. aeruginosa and A. baumannii, although sulbactam-durlobactam and pipeline agents are expanding the therapeutic landscape. We highlight the widening gap between disease burden and access to rapid diagnostics and novel therapies, particularly in high-burden low- and middle-income settings. Finally, we outline the bundled infection prevention and antimicrobial stewardship interventions needed to contain transmission and preserve the effectiveness of novel agents.