Bacteriophage treatment of intransigent diabetic toe ulcers: a case series

Objective: Diabetic foot ulcer (DFU) infections are a growing public health problem, with increasing prevalence, poor response to antibiotics and bacterial resistance to traditional antimicrobials leading to increased morbidity and mortality. Bacteriophages (phages), the viruses that target specific bacteria, are one option for addressing bacterial infections, especially where antibiotics fail. Of particular value is a class of virulent staphylococcal phages that hit almost all Staphylococcus aureus, including most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here we report a continuous case series assessing the effectiveness of treating infected and poorly vascularised toe ulcers with exposed bone, after failure of recommended antibiotic therapy, using topically applied Staphylococcus aureus-specific phage. Method: This was a compassionate-use case series of nine patients with diabetes and poorly perfused toe ulcers containing culture-proven Staphylococcus aureus infected bone and soft tissue, who had responded poorly to recommended antibiotic therapy. Six representative cases are presented here. The only generally accepted other option in each case was toe amputation. Exposed portions of the infected phalanges were removed in three cases and left in place in two cases. One case presented as a micro-clot induced gangrene following vascular stenting. In this case, phage were used to prevent infection. The phage used was a commercially available fully sequenced preparation of staphylococcal phage Sb-1. Phage solution was applied topically to the ulcerations once weekly, following standard good wound care. The amount of phage solution applied varied from 0.1 to 0.5 cc depending on volume and area of the ulceration. Results: All infections responded to the phage applications and the ulcers healed in an average of seven weeks with infected bone debridement. One ulcer, where vascularity was extremely poor and bone was not removed to preserve hallux function, required 18 weeks of treatment. In the case of the toe with the micro-clot gangrene, the toe was salvaged and healed in seven weeks without complications. Conclusion: Topical application of a staph mono-phage preparation can be used successfully to treat infected toe ulcerations with bone involvement, despite very poor vascularity and failure of antibiotic treatment. The success within this small series provides the groundwork for controlled clinical trials of staph phage for diabetic foot infections.