Bacteriophage and Fusidic Acid Have Synergistic Effect Against Meticillin-Resistant Staphylococcus pseudintermedius in Ex Vivo Canine Dermis Model.

Abstract

Background: Antimicrobial stewardship has become vital given the progressive emergence of multidrug-resistant bacteria, and novel approaches to the treatment of bacterial infections are needed. Recently, reported synergistic effects of antibacterial drugs and bacteriophage therapy have revealed promising applications for the management of meticillin-resistant staphylococcal infections.

Objectives: The objective of this study was to investigate the response of meticillin-resistant Staphylococcus pseudintermedius (MRSP) to treatment with a newly isolated, lytic MRSP-specific bacteriophage. Furthermore, a postulated synergism between phage and fusidic acid was examined in a canine ex vivo dermis model.

Material and methods: Skin was harvested from the lateral thorax of a euthanised dog, clipped, the subcutis removed, and epidermis cleaved via a modified salt-split technique. The ex vivo dermis model established in Franz diffusion cells was inoculated with 1 × 10⁷ colony-forming units (cfu) of a clinical MRSP strain for 16 h. Then, experimental groups were treated with phage vB_SpsS_LmqsKl44-4 at a concentration of 2 × 10⁶ plaque-forming units and fusidic acid 0.4 mg alone or in combination for an additional 8 h.

Results: Histopathological results showed that colonies of MRSP reached the superficial dermis and entered hair follicles. Co-treatment with fusidic acid and phage significantly reduced the amount of MRSP after 8 h.

Conclusions and clinical relevance: In conclusion, topical co-treatment with fusidic acid and a phage could be a promising approach to the treatment of canine MRSP pyoderma.