Comparative activities of vancomycin, tigecycline and rifampin in a rat model of methicillin-resistant Staphylococcus aureus osteomyelitis

Abstract

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. 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. 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. 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.