Efficacy of phage cocktail AB-SA01 therapy in diabetic mouse wound infections caused by multidrug-resistant Staphylococcus aureus.
Legesse Garedew Kifelew, Morgyn S Warner, Sandra Morales, Lewis Vaughan, Richard Woodman, Robert Fitridge, James G Mitchell, Peter Speck
Author Information
Legesse Garedew Kifelew: College of Science and Engineering, Flinders University, Adelaide, South Australia, Australia. legesse.kifelew@flinders.edu.au. ORCID
Morgyn S Warner: Infectious Diseases Unit, The Queen Elizabeth Hospital, Woodville, South Australia, Australia.
Sandra Morales: AmpliPhi Biosciences Corporation, Sydney, New South Wales, Australia.
Lewis Vaughan: Research Development and Support, Flinders University, Adelaide, South Australia, Australia.
Richard Woodman: College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
Robert Fitridge: Discipline of Surgery, The University of Adelaide, Adelaide, South Australia, Australia.
James G Mitchell: College of Science and Engineering, Flinders University, Adelaide, South Australia, Australia.
Peter Speck: College of Science and Engineering, Flinders University, Adelaide, South Australia, Australia.
BACKGROUND: diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus. Antibiotic-resistantStaphylococcus aureus is frequently isolated from DFUinfections. 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 clinical trials, in treatment of multidrug-resistant (MDR) S. aureusinfections. 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. At the end of the treatment period, there was a significant decrease (p < 0.001) in bacterial load and wound size in infected phage- and vancomycin-treated groups compared with infected saline-treated mice. In phage-treated mice, wound healing was seen similar to vancomycin treatment. No mortality was recorded associated with infections, and post-mortem examinations did not show any evident pathological lesions other than the skin wounds. No adverse effects related to the application of phages were observed. CONCLUSION: Topical application of phage cocktail AB-SA01 is effective, as shown by bacterial load reduction and wound closure, in the treatment of diabeticwound infections caused by MDR S. aureus. Our results suggest that topical phage cocktail treatment may be effective in treating antibiotic-resistantS. aureusDFUinfections.
