Comparative evaluation of tigecycline and vancomycin, with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model

Abstract

<I>Objectives</I>: <I>Staphylococcus aureus</I> is the most common organism isolated in osteomyelitis. Methicillin-resistant <I>S. aureus</I> (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. <I>Methods</I>: A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 106 colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed. <I>Results</I>: Rabbits that received tigecycline and oral rifampicin therapy (<I>n</I>=14) showed a 100% infection clearance. Rabbits treated with tigecycline (<I>n</I>=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (<I>n</I>=10) also showed a 90% clearance. Rabbits treated with vancomycin (<I>n</I>=11) showed an 81.8% clearance. Untreated controls (<I>n</I>=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. <I>Conclusions</I>: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.