Mechanisms, Significance, Detection and Emerging Therapies for Carbapenem-Resistant Enterobacterales: A Scoping Review.

Abstract

Background: Carbapenems are among the most important broad-spectrum β-lactam antibiotics for the treatment of severe infections caused by multi-drug-resistant Gram-negative bacteria. However, the global emergence and dissemination of carbapenem-resistant Enterobacterales (CRE), particularly carbapenemase-producing Enterobacterales (CPE), have significantly compromised their clinical utility. Resistance is primarily driven by the acquisition of genes encoding carbapenemases, often in combination with porin alterations, efflux pump overexpression and AmpC hyperproduction, resulting in limited treatment options and increased morbidity and mortality.

Objectives: This scoping review aimed to synthesise current evidence on the molecular mechanisms of carbapenem resistance, the classification and epidemiology of carbapenemases, advances in diagnostic approaches and emerging therapeutic strategies for CRE infections.

Methods: A scoping review was conducted in accordance with the PRISMA extension for Scoping Reviews (PRISMA-ScR). Literature published between January 2005 and March 2026 was identified through systematic searches of PubMed/MEDLINE, Scopus and Google Scholar. Eligible studies included original research articles, surveillance reports, systematic reviews and clinical guidelines addressing carbapenem resistance mechanisms, carbapenemase epidemiology, diagnostics or treatment strategies. Data were extracted and synthesised using a narrative and thematic approach.

Results: Carbapenemase production was identified as the predominant mechanism of resistance among CRE, with KPC, NDM, OXA-48-like, VIM and IMP enzymes driving global dissemination. Considerable geographical variation exists in carbapenemase distribution, reflecting differences in antimicrobial use, surveillance capacity and healthcare infrastructure. Advances in molecular diagnostics, including polymerase chain reaction, loop-mediated isothermal amplification, whole-genome sequencing and rapid immunochromatographic assays, have improved detection and surveillance. Emerging therapeutic options, particularly novel β-lactam/β-lactamase inhibitor combinations and cefiderocol, have expanded treatment possibilities, although resistance to newer agents continues to emerge.

Conclusions: CREs remain a major global public health threat. Strengthened surveillance systems, improved access to rapid diagnostics, carbapenemase-directed therapeutic strategies and continued antimicrobial development are essential to limit the spread of resistance and improve clinical outcomes.