Beyond Antibiotics: Emerging Therapies for Pseudomonas aeruginosa in Diabetic Foot Infections

Abstract

Diabetic foot infections (DFIs) caused by Pseudomonas aeruginosa are notoriously difficult to treat due to multidrug resistance, biofilm formation, and impaired tissue perfusion. This narrative review summarises emerging non-antibiotic and adjunctive therapies beyond conventional antimicrobial regimens. We highlight the potential of bacteriophage therapy, antimicrobial peptides, quorum sensing inhibitors, biofilm-disrupting enzymes, nanotechnology-based delivery systems, monoclonal antibodies, iron metabolism inhibitors, and photodynamic therapy. Each of these offers unique mechanisms to disrupt biofilms, neutralise virulence, or enhance immune clearance. In addition, we review advanced localized delivery platforms and diagnostic-guided personalized regimens optimizing intra-wound efficacy. Most of these novel interventions remain investigational, based on preclinical models, early-phase trials, or case reports. Nevertheless, they appear promising in managing chronic, refractory P. aeruginosa DFIs. Integration of these strategies into clinical practice will depend on robust clinical trials, regulatory clarity, and precision diagnostics. By moving beyond antibiotics, this evolving therapeutic landscape offers hope for improved outcomes in a population at high risk for limb loss and systemic complications.