Feasibility and Potential Clinical Ramifications of Using Bacteriophage Therapy for S. aureus Necrotizing Fasciitis

<b>Background:</b><i>Staphylococcus aureus</i> necrotizing fasciitis is a life-threatening infection requiring aggressive surgical and medical management. Despite these interventions, tremendous morbidity and mortality occur. Thus, novel agents are needed to reduce these negative outcomes. Consequently, the aims of this translational study were to evaluate the feasibility of using bacteriophages and the potential clinical ramifications of using bacteriophages in treatment of <i>S. aureus</i> necrotizing fasciitis. <b>Methods:</b> Necrotizing fasciitis clinical isolates (n = 6) were tested against different Staphylococcal bacteriophages (n = 4) to assess for activity. After exposure to bacteriophages that had growth inhibition for more than 16 h, the ability of <i>S. aureus</i> to change phenotypic expression of numerous enzymes was evaluated, and the ability to reduce bacterial virulence was measured with the <i>Caenorhabditis elegans</i> assay. <b>Results:</b> Staphylococcal myoviridae bacteriophages were able to lyse most clinical isolates (83%). Interestingly, after exposure to myoviridae bacteriophages, <i>S. aureus</i> isolates had no expression of hemolysin, secreted coagulase, or lecthinase, or the ability to ferment mannitol. These same bacteriophages also caused statistically significant decreases in bacterial virulence (<i>p</i> < 0.05). Neither findings were observed for bacteriophages of the podoviridae family. <b>Conclusions:</b> To use bacteriophages for <i>S. aureus</i> necrotizing fasciitis, cocktails of Staphylococcal myoviridae are likely needed to allow for broad host ranges, mitigating the need for in vitro sensitivity testing. Moreover, Staphylococcal myoviridae have the potential to reduce specific enzyme expression and global virulence of residual <i>S. aureus</i>. Thus, bacteriophages may aid in reducing necrotizing fasciitis morbidity by not only lysing <i>S. aureus</i> but also by reducing <i>S. aureus</i> virulence.