Effects of bacteriophage and antibiotic treatments in rats with experimental spondylodiscitis model created by MRSA

BACKGROUND: Bacteriophage therapy, which is a very old treatment method in the treatment of pyogenic infections caused by multi-drug resistant bacteria, has begun to be considered as a "new" alternative. In our study, we aimed to show the effects of bacteriophage treatment objectively and to guide experimental and clinical studies. METHODS: In the study, 40 Wistar-Albino 12-14 week old female (250-300 g) rats were randomly divided into 4 groups. Groups were named as Group 1(Control), Group 2(Vancomycin), Group 3(Phage), Group 4(Vancomycin/Phage). Under anesthesia, 0.05 ml of 107 CFU/ml ADU26 MRSA agent was inoculated into the vertebral disc space in the proximal tail region. The development of spondylodiscitis was demonstrated 10 days after the operation with imaging performed with T1, T2 and STIR sequences in MRI. The rats with observed infection were treated according to the previously planned protocols. Control MRI was taken on the 28th day. After imaging, under anesthesia, the marked discs of the rats, including the lower and upper vertebrae and discs, were excised as blocks for examination in the pathology laboratory. In statistical analysis, Kruskal-Wallis, Wilcoxon, Dwass-Steel-Critchlow-Fligner pairwise comparison and Spearman Correlation Analysis tests were used. RESULTS: In the first MRI performed to show the development of infection 10 days after bacterial inoculation, no significant difference was found between the infection levels of the groups in terms of MRI scoring, and it was observed that they were equivalent to each other in terms of infection development. (p=0.552) In the paired analyzes, it was determined that the phage+vancomycin treated group and the phage therapy group showed a significant improvement in MRI scoring compared to the control group. (p=0.013; p=0.026) In paired analyzes made in terms of histopathological scoring; In the phage+vancomycin treated group; There was a significant difference in improvement compared to the control group, the phage therapy group and the vancomycin applied groups. (p<0.001; p=0.049; p=0.027) In paired analyzes made in terms of histopathological scoring; A significant improvement was observed in the phage+vancomycin treated group compared to the control group, phage therapy and vancomycin applied groups. (p<0.001; p=0.049; p=0.027). The correlation between the control MRI scores performed after the treatment methods of the subjects and the histopathological scoring of the tissues obtained after the treatment was evaluated. Control MRI scores and histopathological scores showed moderate correlation in a positive direction. (r=0.419; p=0.007) CONCLUSİONS: In our experimental spondylodiscitis model, it has been shown that the combination of bacteriophage and antibiotic therapy is superior to phage-only and antibiotherapy-only protocols histopathologically and radiologically. Keywords: Spondylodiscitis, bacteriophage, phage,vancomycin