title: Activity of Tedizolid in Methicillin-Resistant Staphylococcus aureus Experimental Foreign Body-Associated Osteomyelitis.
abstract: We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n = 14), tedizolid plus rifampin (n = 11), rifampin (n = 16), or vancomycin plus rifampin (n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 μg/ml and 60 μg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 μg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.
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 Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jayawant
authors.initials: J
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 / Q000097:blood / Q000493:pharmacokinetics*; D058491:Bacterial Load / Q000187:drug effects; D001864:Bone Wires; D004195:Disease Models, Animal; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D005547:Foreign Bodies / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity; D008826:Microbial Sensitivity Tests; D010755:Organophosphates / Q000097:blood / Q000493:pharmacokinetics*; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D010080:Oxazoles / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013977:Tibia / Q000187:drug effects / Q000293:injuries / Q000382:microbiology; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D010755:Organophosphates; D010080:Oxazoles; D014640:Vancomycin; C515040:tedizolid phosphate; D012293:Rifampin