Efficacy of Phage Cocktail AB-SA01 Therapy in Diabetic Mouse Wound Infections Caused by Multidrug-Resistant Staphylococcus aureus

Abstract Background: Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus. Antibiotic-resistant Staphylococcus aureus is frequently isolated from DFU infections. Bacteriophages (“phages”) represent an alternative or adjunct treatment to antibiotic therapy. Here we describe the efficacy of AB-SA01, a cocktail of three S. aureus Myoviridae phages, made to current good manufacturing practice (cGMP) standards, and which has undergone two phase I trials, in treatment of multidrug-resistant (MDR) S. aureus infections.Methods: Using a diabetic mouse model, bilateral six-millimetre excisional deep skin wounds inflicted on the dorsum of Balb/c mice were infected with 6.7 log10 colony-forming units (CFU) of clinical MDR S. aureus. Infections were treated topically with AB-SA01, or controls: saline, or saline plus intraperitoneal (IP) vancomycin. Bacterial load and wound healing parameters were used to assess treatment efficacy.Results: Wounds of saline-treated mice showed no healing, but expanded and became inflamed, ulcerated, and suppurating. In contrast, AB-SA01 treatment decreased the bacterial load with efficacy similar or superior to vancomycin treatment. In phage-treated mice, wound healing was seen similar to vancomycin treatment. No adverse effects related to the application of phages were observed.Conclusion: Our results suggest that topical phage cocktail treatment may be effective in treating antibiotic-resistant S. aureus DFU infections.