TY - JOUR
T1 - Bacteriophage Therapy for the Prevention and Treatment of Fracture-Related Infection Caused by Staphylococcus aureus
T2 - A Preclinical Study
AU - Onsea, Jolien
AU - Post, Virginia
AU - Buchholz, Tim
AU - Schwegler, Hella
AU - Zeiter, Stephan
AU - Wagemans, Jeroen
AU - Pirnay, Jean Paul
AU - Merabishvili, Maya
AU - D'Este, Matteo
AU - Rotman, Stijn G.
AU - Trampuz, Andrej
AU - Verhofstad, Michael H.J.
AU - Obremskey, William T.
AU - Lavigne, Rob
AU - Richards, R. Geoff
AU - Moriarty, T. Fintan
AU - Metsemakers, Willem Jan
N1 - Publisher Copyright:
© 2021 Onsea et al.
PY - 2021/12
Y1 - 2021/12
N2 - Although several studies have shown promising clinical outcomes of phage therapy in patients with orthopedic device-related infections, questions remain regarding the optimal application protocol, systemic effects, and the impact of the immune response. This study provides a proof-of-concept of phage therapy in a clinically relevant rabbit model of fracture-related infection (FRI) caused by Staphylococcus aureus. In a prevention setting, phage in saline (without any biomaterial-based carrier) was highly effective in the prevention of FRI, compared to systemic antibiotic prophylaxis alone. In the subsequent study involving treatment of established infection, daily administration of phage in saline through a subcutaneous access tube was compared to a single intraoperative application of a phage-loaded hydrogel and a control group receiving antibiotics only. In this setting, although a possible trend of bacterial load reduction on the implant was observed with the phage-loaded hydrogel, no superior effect of phage therapy was found compared to antibiotic treatment alone. The application of phage in saline through a subcutaneous access tube was, however, complicated by superinfection and the development of neutralizing antibodies. The latter was not found in the animals that received the phage-loaded hydrogel, which may indicate that encapsulation of phages into a carrier such as a hydrogel limits their exposure to the adaptive immune system. These studies show phage therapy can be useful in targeting orthopedic device-related infection, however, further research and improvements of these application methods are required for this complex clinical setting.
AB - Although several studies have shown promising clinical outcomes of phage therapy in patients with orthopedic device-related infections, questions remain regarding the optimal application protocol, systemic effects, and the impact of the immune response. This study provides a proof-of-concept of phage therapy in a clinically relevant rabbit model of fracture-related infection (FRI) caused by Staphylococcus aureus. In a prevention setting, phage in saline (without any biomaterial-based carrier) was highly effective in the prevention of FRI, compared to systemic antibiotic prophylaxis alone. In the subsequent study involving treatment of established infection, daily administration of phage in saline through a subcutaneous access tube was compared to a single intraoperative application of a phage-loaded hydrogel and a control group receiving antibiotics only. In this setting, although a possible trend of bacterial load reduction on the implant was observed with the phage-loaded hydrogel, no superior effect of phage therapy was found compared to antibiotic treatment alone. The application of phage in saline through a subcutaneous access tube was, however, complicated by superinfection and the development of neutralizing antibodies. The latter was not found in the animals that received the phage-loaded hydrogel, which may indicate that encapsulation of phages into a carrier such as a hydrogel limits their exposure to the adaptive immune system. These studies show phage therapy can be useful in targeting orthopedic device-related infection, however, further research and improvements of these application methods are required for this complex clinical setting.
KW - Bacteriophages
KW - Fracture-related infection
KW - Implant
KW - Rabbit
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=85122743682&partnerID=8YFLogxK
U2 - 10.1128/spectrum.01736-21
DO - 10.1128/spectrum.01736-21
M3 - Article
C2 - 34908439
AN - SCOPUS:85122743682
SN - 2165-0497
VL - 9
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 3
M1 - e01736-21
ER -