title: Vancomycin-rifampin combination therapy has enhanced efficacy against an experimental Staphylococcus aureus prosthetic joint infection.
abstract: Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.
authors.affiliation: Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Jared A
authors.initials: JA
authors.lastname: Niska
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Shahbazian
authors.forename: Romela Irene
authors.initials: RI
authors.lastname: Ramos
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Francis
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Bernthal
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016459:Prosthesis-Related Infections / Q000188:drug therapy*; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity*; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D012293:Rifampin
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