title: Rifampin-Based Combination Therapy Is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy.
abstract: Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Brinkman
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Suzannah M
authors.initials: SM
authors.lastname: Schmidt-Malan
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jayawant N
authors.initials: JN
authors.lastname: Mandrekar
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA patel.robin@mayo.edu.|Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Patel
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D004359:Drug Therapy, Combination; D005547:Foreign Bodies / Q000382:microbiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D017208:Rats, Wistar; D012293:Rifampin / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D012293:Rifampin
keywords: MRSA; osteomyelitis; prosthetic joint infection; rifampin resistance