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Efflux-mediated carbapenem resistance: unveiling genetic drivers, clinical implications, and strategies for global antimicrobial stewardship.

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Τίτλος: Efflux-mediated carbapenem resistance: unveiling genetic drivers, clinical implications, and strategies for global antimicrobial stewardship.
Συγγραφείς: Jangid H; Department of Microbiology, School of Sciences, JECRC University, Jaipur, 303905, India., Menghani E; Department of Biotechnology, School of Sciences, JECRC University, Jaipur, Rajasthan, 303905, India., Saini KC; Department of Biotechnology, School of Sciences, JECRC University, Jaipur, Rajasthan, 303905, India., Verma AK; Department of Biotechnology, School of Sciences, JECRC University, Jaipur, Rajasthan, 303905, India. abhishek.verma@jecrcu.edu.in.
Πηγή: Antonie van Leeuwenhoek [Antonie Van Leeuwenhoek] 2026 Aug 03; Vol. 119 (9). Date of Electronic Publication: 2026 Aug 03.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer Country of Publication: Netherlands NLM ID: 0372625 Publication Model: Electronic Cited Medium: Internet ISSN: 1572-9699 (Electronic) Linking ISSN: 00036072 NLM ISO Abbreviation: Antonie Van Leeuwenhoek Subsets: MEDLINE
Imprint Name(s): Publication: 2004- : Berlin : Springer
Original Publication: Wageningen, Netherland [etc.] Veenman [etc.]
Ιατρικοί όροι (MeSH): Carbapenems*/pharmacology , Anti-Bacterial Agents*/pharmacology , Gram-Negative Bacteria*/drug effects , Gram-Negative Bacteria*/genetics , Gram-Negative Bacteria*/metabolism , beta-Lactam Resistance*/genetics , Antimicrobial Stewardship*, Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Gram-Negative Bacterial Infections/drug therapy ; Gram-Negative Bacterial Infections/microbiology ; beta-Lactamases/genetics ; beta-Lactamases/metabolism ; Humans ; Drug Resistance, Multiple, Bacterial
Περίληψη: Although carbapenems are still key drugs in the treatment of serious infections due to MDR Gram-negative bacteria, the high rate of emergence of carbapenem resistance is a serious global health concern. Carbapenemase production is well studied but so far efflux pumps play an important, yet underestimated role in the development of resistance. Efflux systems, especially those belonging to the resistance-nodulation-division family play a role in intrinsic and acquired resistance by actively expelling antibiotics and synergizing with other mechanisms like loss of porins and enzyme degradation, and biofilm formation. This review will offer a detailed and integrated perspective of efflux-mediated carbapenem resistance including the structure, regulation and genetic determinants of efflux activity. Special attention is given to the interplay of efflux pumps and co-resistance mechanisms which indicates that those mechanisms do not act as independent mechanisms but are embedded in a network of co-ordinated resistance. The review also covers new approaches to therapy such as efflux pump inhibitors and critically discusses the problems that hinder their use in the clinic. Importantly, this work reveals some important limitations with the current diagnostic methods, showing that efflux-mediated resistance is often underestimated due to a lack of standardized methods. Moreover, the drivers of efflux activity from an epidemiological and environmental perspective are discussed within a One Health context, such as antibiotic pressure and co-selection by heavy metals. This review aims to combine mechanistic, clinical and ecological aspects to present a more nuanced view of efflux-mediated resistance and highlights the need for better diagnostics, focused treatment strategies and overall antimicrobial stewardship to manage carbapenem resistance infections.
(© 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Competing Interests: Declarations. Conflicts of interest: The authors declare no conflict of interest. Ethical approval: Not applicable. Human and animal participants: This article does not contain any studies with human or animal subjects. Clinical trial number: Not applicable.
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Contributed Indexing: Keywords: Antibiotic stewardship; Carbapenem resistance; Efflux pump inhibitors; Efflux pumps; Multidrug resistance
Substance Nomenclature: 0 (Carbapenems)
0 (Anti-Bacterial Agents)
0 (Bacterial Proteins)
EC 3.5.2.6 (carbapenemase)
0 (Membrane Transport Proteins)
EC 3.5.2.6 (beta-Lactamases)
Entry Date(s): Date Created: 20260803 Date Completed: 20260803 Latest Revision: 20260905
Update Code: 20260905
DOI: 10.1007/s10482-026-02394-8
PMID: 42545426
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1572-9699
DOI:10.1007/s10482-026-02394-8