In vitro synergism of fosfomycin and clarithromycin antimicrobials against methicillin-resistant Staphylococcus pseudintermedius

BACKGROUND: Bacterial biofilms are of tremendous concern for clinicians, as they can compromise the ability of the immune system and antimicrobial therapy to resolve chronic and recurrent infections. Novel antimicrobial therapies or combinations targeted against biofilm establishment and growth subsequently represent a promising new option for the treatment of chronic infectious diseases. In this study, we treated bacterial biofilms produced by methicillin-resistant Staphylococcus pseudintermedius (MRSP) with a combination of fosfomycin and clarithromycin. We selected these agents, because they prevent biofilm formation and induce antimicrobial synergism that may also target other staphylococci. RESULTS: We determined that the combination of fosfomycin and clarithromycin better impairs S. pseudintermedius biofilm formation compared to treatment with either therapy alone (P < 0.05). Morphological examination of these biofilms via scanning electron microscopy demonstrated that fosfomycin alone does impact biofilm formation on orthopaedic implants. However, this activity is enhanced in the presence of clarithromycin. We propose that the bacteriostatic activity of clarithromycin is accentuated when fosfoymcin is present, as it may allow better penetration into the biofilm matrix, allowing fosfomycin access to sessile bacteria near the surface of attachment. CONCLUSIONS: Here, we demonstrate that the combination of fosfomycin and clarithromycin may be a useful therapy that could improve the clinical outcomes of treating antimicrobial resistant MRSP biofilms.