title: Daptomycin combinations as alternative therapies in experimental foreign-body infection caused by meticillin-susceptible Staphylococcus aureus.
abstract: Whilst levofloxacin (LVX) in combination with rifampicin (RIF) is considered the optimal treatment for prosthetic joint infection (PJI) caused by meticillin-susceptible Staphylococcus aureus (MSSA), no therapeutic alternatives have been accurately evaluated. Based on the high effectiveness of the combination of daptomycin (DAP) plus RIF against meticillin-resistant S. aureus (MRSA) in this setting, in this study the efficacy of DAP+RIF and DAP+LVX combinations was tested as alternative therapies for foreign-body infections (FBIs) caused by MSSA. A tissue-cage infection model was performed using an MSSA strain. Male Wistar rats were treated for 7 days with LVX, DAP, RIF or the combinations LVX+RIF, DAP+RIF and DAP+LVX. Antibiotic efficacy was evaluated by bacterial counts from tissue cage fluid (TCF) and the cure rate was determined from adhered bacteria. Resistance was screened. Monotherapies were less effective than combinations (P<0.05), and resistance to DAP and RIF emerged. DAP+RIF (decrease in bacterial counts in TCF, -4.9logCFU/mL; cure rate, 92%) was the most effective therapy (P<0.05). There were no differences between LVX+RIF (-3.4logCFU/mL; 11%) and DAP+LVX (-3.3logCFU/mL; 47%). No resistant strains appeared with combined therapies. In conclusion, the combinations DAP+RIF and DAP+LVX showed good efficacy and prevented resistance. DAP+RIF provided higher efficacy than LVX+RIF. These DAP combinations were efficacious alternatives therapies for MSSA FBI. Further studies should confirm whether DAP+RIF may be useful as a first-line therapy in the setting of PJI caused by MSSA.
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: 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 de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Murillo
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Ribera
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Vivas
authors.affiliation: Department of Microbiology, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Garcia-Somoza
authors.affiliation: Department of Microbiology, IDIBELL, Hospital Universitari de Bellvitge and CIBERES ISCIII, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cabellos
authors.affiliation: Department of Orthopaedic Surgery, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cabo
authors.affiliation: Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ariza
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015169:Colony Count, Microbial; D000529:Complementary Therapies / Q000379:methods*; D017576:Daptomycin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D005547:Foreign Bodies / Q000150:complications*; D064704:Levofloxacin / Q000008:administration & dosage; D008297:Male; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D017576:Daptomycin; D012293:Rifampin
keywords: Combination therapy; Daptomycin; Foreign-body infection; MSSA