Management of Diabetic Foot Infections Using Phage Therapy

Abstract: Diabetic foot infections (DFIs) represent a major and increasing complication of diabetes mellitus, often leading to hospitalization, osteomyelitis, and lower limb amputation. The rising prevalence of multidrug-resistant pathogens in DFIs has limited the effectiveness of conventional antibiotic therapy, emphasizing the need for alternative or adjunctive approaches. Bacteriophage therapy has emerged as a promising strategy due to its specificity to target bacteria, ability to penetrate and disrupt biofilms, and activity against multidrug-resistant organisms, while generally demonstrating a favorable safety profile with minimal effects on host tissues. This review critically evaluates current evidence for phage therapy in DFIs, which is dominated by in vitro studies, animal models, and a limited number of compassionate use and small clinical series. Reported outcomes show effectiveness against key pathogens including Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli , and Enterococcus species, with preliminary evidence of reduced bacterial burden and improved wound healing in select patients. Despite these encouraging findings, clinical translation is challenged by narrow phage host ranges, the need for rapid phage-pathogen matching, standardization of production, regulatory hurdles, and incomplete understanding of pharmacokinetics and host immune interactions. Therefore, while phage therapy represents a potentially safe and effective adjunct to conventional DFI management, further well-designed preclinical studies and randomized clinical trials, alongside optimized delivery systems and regulatory frameworks, are required to fully establish its clinical utility. Keywords: diabetic foot infections, phage therapy, antibiotics