title: Causes and Implications of the Disappearance of Rifampin Resistance in a Rat Model of Methicillin-Resistant Staphylococcus aureus Foreign Body Osteomyelitis.
abstract: Orthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistant Staphylococcus aureus (MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alone in vitro or in vivo demonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria. In vivo, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (P = 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (P = 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.
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 Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Harmony L
authors.initials: HL
authors.lastname: Tyner
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 Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA patel.robin@mayo.edu.
authors.forename: Robin
authors.initials: R
authors.lastname: Patel
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005547:Foreign Bodies / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008712:Methicillin / Q000494:pharmacology*; D016106:Methicillin Resistance / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D008712:Methicillin; D012293:Rifampin