title: The anti-biofilm effect of macrolides in a rat model of S. aureus foreign-body infection: Might it be of clinical relevance?
abstract: Using a tissue cage infection rat model, we test the anti-biofilm effect of clarithromycin on the efficacy of daptomycin and a daptomycin + rifampicin combination against methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In vitro: kill curves, daptomycin exposure studies and clarithromycin activity against biofilm were studied. In vivo: the efficacies of clarithromycin, daptomycin or daptomycin + clarithromycin, daptomycin + rifampicin and daptomycin + rifampicin + clarithromycin combinations were evaluated. In vitro: the addition of clarithromycin to daptomycin improved its activity only against one MRSA strain. Changes in daptomycin MIC values appeared more quickly in MSSA than in MRSA strain, and this was not modified by clarithromycin. Clarithromycin prevented biofilm formation but did not eradicate it. In vivo: the daptomycin + rifampicin combination was the most effective treatment and was not improved by the addition of clarithromycin. Daptomycin and daptomycin + clarithromycin had similar effectiveness; the combination protected against the appearance of daptomycin resistance only in one MRSA strain. Using a staphylococcal foreign-body infection model, we observed a slight effect with the addition of clarithromycin to daptomycin, which resulted in protection against the appearance of daptomycin-resistant strains. However, efficacy was not improved. Overall, our findings do not support a relevant clinical role for macrolides in treating device-related staphylococcal infections based on their anti-biofilm effect.
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL-Hospital Universitari Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain. celhaj@idibell.cat.
authors.forename: Cristina
authors.initials: C
authors.lastname: El Haj
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL-Hospital Universitari Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.|Spanish Network for the Research in Infectious Diseases (REIPIRD12/0015), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Murillo
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL-Hospital Universitari Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Ribera
authors.affiliation: Department of Microbiology, IDIBELL-Hospital Universitari Bellvitge, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Garcia-Somoza
authors.affiliation: Department of Microbiology, IDIBELL-Hospital Universitari Bellvitge, Barcelona, Spain.|Department of Microbiology, CIBERES ISCIII, Madrid, Spain.
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL-Hospital Universitari Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.|Spanish Network for the Research in Infectious Diseases (REIPIRD12/0015), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cabellos
authors.affiliation: Orthopaedic Surgery Service, IDIBELL-Hospital Universitari Bellvitge, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cabo
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL-Hospital Universitari Bellvitge, Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.|Spanish Network for the Research in Infectious Diseases (REIPIRD12/0015), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ariza
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D017291:Clarithromycin / Q000008:administration & dosage* / Q000494:pharmacology; D017576:Daptomycin / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000379:methods; D005547:Foreign Bodies / Q000150:complications*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D051381:Rats; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin; D017576:Daptomycin; D012293:Rifampin
keywords: Biofilm; Clarithromycin; Foreign-body infection; S. aureus