title: In vitro synergism of fosfomycin and clarithromycin antimicrobials against methicillin-resistant Staphylococcus pseudintermedius.
abstract: 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.
authors.forename: Matthew
authors.initials: M
authors.lastname: DiCicco
authors.affiliation: BioNano Laboratory, School of Engineering, University of Guelph, Guelph N1G 2 W1, Canada. sneethir@uoguelph.ca.
authors.forename: Suresh
authors.initials: S
authors.lastname: Neethirajan
authors.forename: J Scott
authors.initials: JS
authors.lastname: Weese
authors.forename: Ameet
authors.initials: A
authors.lastname: Singh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D017291:Clarithromycin / Q000494:pharmacology*; D004285:Dogs; D004357:Drug Synergism; D005578:Fosfomycin / Q000494:pharmacology*; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D013203:Staphylococcal Infections / Q000382:microbiology / Q000662:veterinary; D013210:Staphylococcus / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology / Q000648:ultrastructure
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D017291:Clarithromycin