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

Abstract

Objectives: 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.

Keywords: Osteomyelitis; Rifampin; Staphylococcus aureus; Tigecycline; Vancomycin.