Bacteriophage Therapy for the Prevention and Treatment of Fracture-Related Infection Caused by Staphylococcus aureus: a Preclinical Study
Jolien Onsea, Virginia Post, Tim Buchholz, Hella Schwegler, Stephan Zeiter, Jeroen Wagemans, Jean‐Paul Pirnay, Maya Merabishvili, Matteo D’Este, Stijn G. Rotman, Andrej Trampuž, M.H.J. Verhofstad, William T. Obremskey, Rob Lavigne, R. Geoff Richards, T. Fintan Moriarty, Willem‐Jan Metsemakers
Abstract
Because of the growing spread of antimicrobial resistance, the use of alternative prevention and treatment strategies is gaining interest. Although the therapeutic potential of bacteriophages has been demonstrated in a number of case reports and series over the past decade, many unanswered questions remain regarding the optimal application protocol. Furthermore, a major concern during phage therapy is the induction of phage neutralizing antibodies. This study aimed at providing a proof-of-concept of phage therapy in a clinically relevant rabbit model of fracture-related infection caused by Staphylococcus aureus. Phage therapy was applied as prophylaxis in a first phase, and as treatment of an established infection in a second phase. The development of phage neutralizing antibodies was evaluated in the treatment study. This study demonstrates that phage therapy can be useful in targeting orthopedic device-related infection, especially as prophylaxis; however, further research and improvements of these application methods are required.