Antibiotic resistance genes in diabetic foot ulcer microbiomes: Molecular mechanisms and clinical management strategies

Fitra  Adi Prayogo

Authors

Fitra Adi Prayogo Biomedical Sciences Study Program, Faculty of Nursing and Health Sciences, Karya Husada University, Indonesia

Keywords:

Antibiotic resistance genes, antimicrobial resistance, diabetic foot ulcer, microbiome, resistome

Abstract

Background: Diabetic foot ulcers (DFUs) affect 19.0%–34.0% of patients with diabetes during their lifetime, representing a major global health burden with more than 18 million cases annually. The polymicrobial nature of DFU infections, combined with emerging antibiotic resistance genes, poses considerable clinical management challenges. Methicillin-resistant Staphylococcus aureus (MRSA) prevalence reached 84.0% and extended-spectrum beta-lactamase (ESBL) production exceeded 50.0% among gram-negative isolates in some regions, creating urgent therapeutic concerns.

Objectives: This comprehensive review examines the current understanding of microbial communities in DFUs and their associated resistome, analyzes the molecular mechanisms underlying antibiotic resistance, and evaluates the clinical implications to identify evidence-based management strategies.

Methods: A narrative review was conducted using systematic searches of PubMed/MEDLINE, Embase, Web of Science, and Google Scholar from 2014 to 2025. Search strategies utilized MeSH terms, including “diabetic foot ulcer,” “antibiotic resistance genes,” “microbiome,” and “resistome.”

Result(s): Analysis revealed extensive resistome diversity, with individual ulcers harboring dozens of distinct resistance determinants. The predominant resistance genes included mecA (methicillin resistance, 48.7%– 84.0%), blaCTX-M, blaSHV, blaTEM (ESBL production, 26.7%–64.7%), and various fluoroquinolone resistance genes (qnrS, 15.4%). Horizontal gene transfer mechanisms facilitate the rapid dissemination of resistance within polymicrobial biofilm communities, thereby substantially affecting treatment outcomes and increasing treatment failure rates.

Conclusion: Antibiotic resistance in DFUs poses a critical challenge that requires urgent, multifaceted approaches. Future directions should prioritize rapid diagnostic technologies, precision antimicrobial approaches, and innovative therapeutic interventions, including antimicrobial photodynamic therapy and bacteriophage treatment, to address this growing threat.

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