According to the application management of bacteriophagesreach ratios to the target texture and field

AİM: To compare the rate of bacteriophages reaching the target tissue and the site according to the application methods. Materials and Methods: The study was carried out in Mersin University Experimental Animals Research Laboratory. 27 Wistar-Albino rats, 12-14 weeks old male (200-240 g) rats were used in the experiment. The number of experimental animals was determined as a minimum of 24 by taking the type 1 error of 0.05, the test power of 80%, and the effect size of 0.816 by power analysis. Three subjects were separated as the control group. During the study, the subjects were maintained under 24o ambient temperature, 55–60% humidity and 12:12 hour light-dark cycle conditions, and free access to dry food and tap water was provided. Experimentally, a PPE model was created in rats by using Methicillin Resistant Staphylococcus aureus (MRSA). Rats were randomly divided into four groups of six according to the bacteriophage route of administration, as intraperitoneal (IP), intravenous (IV), oral (PO), and local injection (LE). Three rats without PPE model were used as control group. Sb-1 (Eliava Institute, Microbiology and Virology, Tbilisi, Georgia) phage known to be effective against Staphylococcus Aureus was used as bacteriophage. Phage suspension was administered for three days, from 1x10 8 PFU/ml suspension to 0.1 ml/day, as intraperitoneal injection (IP group), intravenous injection into the jugular vein (IV group), oral (PO group) or local injection(LE) at the surgical wound site. . In the control group, one subject was administered intravenous phage suspension for 3 days at the same dose, another intraperitoneally, and the last one oral phage suspension. On the 4th day, the rats were sacrificed by exsanguination, 0.5 cm bone blocks were taken from their proximal tibia and given to the histology laboratory for electromicroscopic studies in tubes containing glutaraldehyde. In addition to bone, liver, kidney, stomach, brain, heart muscle and striated muscle tissue samples were taken from 3 subjects in the control group. Results: Clinical infection developed in all subjects except the control group. In the electron microscopic examination of the control group, bacteriophage clusters were observed in some of the mitochondria located in some proximal tubule epithelial cells only in the kidneys of the subjects administered bacteriophage intravenously, intraperitoneally or orally. It was observed that the normal ultrastructural structure was disrupted in mitochondria with these clusters, and degeneration and loss were 8 observed in normal mitochondrial crystals. There was no significant difference between the groups in terms of the presence of intact bacteria, the number of phagocytized non-phage bacteria, the number of phage-invaded bacteria, the presence of bacteriophage cluster in the field (the rate of phage reaching the site), and the total number of bacteria in the field as a result of the experiment. When the relationship between the total number of bacteria and the number of bacteriophage clusters is evaluated; It was observed that there was a strong positive linear relationship between the total number of bacteria and the number of bacteriophage clusters, independent of the groups. Conclusions: In our experimental animal model study in which we created periprosthetic infection, we did not detect a statistically significant difference between four different routes (intraperitoneal, intravenous, local and oral). We observed a strong positive (linear) relationship between the total number of bacteria and the number of bacteriophage clusters, independent of groups. We determined that in subjects without foci of infection, phages were not observed in other tissue samples except kidney tissue samples. Keywords: Periprosthetic joint infection, bacteriophage, routes of administration of bacteriophages