title: Comparative activities of vancomycin, tigecycline and rifampin in a rat model of methicillin-resistant Staphylococcus aureus osteomyelitis.
abstract: OBJECTIVE
  Implant-associated methicillin-resistant Staphylococcus aureus (MRSA) infections are challenging to treat. We compared antimicrobial activities in a rat model of chronic osteomyelitis in the context of retention of the foreign body without débridement.
  
  
  METHODS
  MRSA was inoculated into the proximal tibia and a wire implanted. Four weeks after infection, treatment with vancomycin 50 mg/kg every 12 h, tigecycline 14 mg/kg every 12 h, rifampin 25 mg/kg every 12 h, or the combination of vancomycin or tigecycline plus rifampin was administered intraperitoneally for 21 days.
  
  
  RESULTS
  MRSA was cultured from all tibias in the control group (median, 6.06 log10 CFU/g bone). Median bacterial counts (log10 CFU/g) at 48 h post-treatment were 6.16 for vancomycin (p = 0.753), 2.29 for vancomycin plus rifampin (p < 0.001), 5.90 for tigecycline (p = 0.270), 0.10 for tigecycline plus rifampin (p < 0.001), and 0.91 for rifampin (p = 0.044) treatment. Three deaths were observed in the tigecycline plus rifampin group. Median bacterial counts (log10 CFU/g) at two weeks post-treatment were 5.65 for vancomycin (p = 0.6), 4.05 for vancomycin plus rifampin (p = 0.105), 5.68 for tigecycline (p = 0.401), 4.05 for tigecycline plus rifampin (p = 0.028), and 5.98 for rifampin (p = 0.297) treatment.
  
  
  CONCLUSIONS
  Tigecycline plus rifampin resulted in a significant bacterial count decrease, an effect more prominent at 48 h than two weeks after treatment completion. Tigecycline was not well tolerated at the dose studied.
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Paschalis
authors.initials: P
authors.lastname: Vergidis
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States.
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, MN 55905, United States.
authors.forename: Jayawant N
authors.initials: JN
authors.lastname: Mandrekar
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Steckelberg
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States; Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN 55905, United States. Electronic address: 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; D006801:Humans; D008297:Male; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D000078304:Tigecycline; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000078304:Tigecycline; D008911:Minocycline; D008712:Methicillin; D012293:Rifampin
keywords: Osteomyelitis; Rifampin; Staphylococcus aureus; Tigecycline; Vancomycin