Effect of Bacteriophage Administration Route on Phage Localization in a Rat MRSA Implant-Associated Infection Model

Background/Objectives: Implant-associated infections are challenging conditions in orthopedic surgery. This experimental study aimed to evaluate phage localization within infected tissues following different routes of administration. Methods: An implant-related infection model was created using methicillin-resistant Staphylococcus aureus (MRSA) in twenty-four rats. Subjects were randomly divided into four groups depending on the bacteriophage administration route. Three rats were designated as the control group. Phage suspension was applied intraperitoneally, intravenously, orally and locally at 0.1 mL/day of 1 × 10⁸ PFU/mL suspension for three consecutive days. In the control group, intravenous, intraperitoneal and oral phage suspensions were administered separately at the same dose for 3 days. After completion of the experiment, tibia samples were taken in the experimental group. Additionally, liver, kidney, stomach, brain, heart muscle and striated muscle tissue samples were taken from the three subjects in the control group. Results: In the control group, unconfirmed phage-like structures were incidentally observed in some mitochondria of renal proximal tubular epithelial cells on transmission electron microscopy. In the experimental group, there was a strong positive linear relationship between the total number of bacteria and the number of bacteriophage clusters, independent of the groups. Conclusions: Bacteriophage clusters were detected in infected tibial tissues after all administration routes, suggesting phage localization at the infection site. Unexpected phage-like clusters were observed within mitochondria of proximal tubular epithelial cells in the control animals. This finding should be regarded as an unconfirmed incidental finding requiring further validation.