title: Activity of Tedizolid in Methicillin-Resistant Staphylococcus epidermidis Experimental Foreign Body-Associated Osteomyelitis.
abstract: We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia, and a stainless steel wire with a precolonized MRSE biofilm was implanted. Following a 1-week infection period, 92 rats received either no treatment (n = 17) or 14 days of intraperitoneal tedizolid (n = 15), tedizolid plus rifampin (n = 15), rifampin (n = 15), vancomycin plus rifampin (n = 15), or vancomycin (n = 15). Quantitative bone and wire cultures were performed after treatment completion and also 1 week after infection in a separate group of five rats. The median quantity of staphylococci in bone after the 1-week infection period was 4.89 log10CFU/g bone (interquartile range, 3.83 to 5.33 log10CFU/g bone); staphylococci were recovered from all associated wires. A median quantity of staphylococci of 3.70 log10CFU/g bone was detected in bones of untreated control rats after 3 weeks. Quantities of staphylococci in bones of all treatment groups except the group receiving vancomycin alone (2.78 log10CFU/g) were significantly lower than those for untreated controls, with no staphylococci being detected in the groups receiving rifampin monotherapy, tedizolid-plus-rifampin combination therapy, and vancomycin-plus-rifampin combination therapy. Quantities of staphylococci on wires from all treatment groups that included rifampin were significantly lower than those for untreated controls. No resistance to rifampin, tedizolid, or vancomycin was detected. Tedizolid combined with rifampin was active in a rat model of MRSE foreign body-associated osteomyelitis.
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.|Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Park
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Kerryl E
authors.initials: KE
authors.lastname: Greenwood-Quaintance
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Audrey N
authors.initials: AN
authors.lastname: Schuetz
authors.affiliation: Division of Biomedical Statistics and Informatics, 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; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005547:Foreign Bodies; D008297:Male; D016106:Methicillin Resistance / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010755:Organophosphates / Q000494:pharmacology*; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D010080:Oxazoles / Q000494:pharmacology*; D017208:Rats, Wistar; D012293:Rifampin / Q000494:pharmacology; D013193:Stainless Steel; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000472:pathogenicity; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; D013193:Stainless Steel; D014640:Vancomycin; C515040:tedizolid phosphate; D012293:Rifampin
keywords: Staphylococcus epidermidis; foreign body; osteomyelitis