Oral rifampin plus azithromycin or clarithromycin to treat osteomyelitis in rabbits

A rabbit model for Staphylococcus aureus osteomyelitis was used to compare 28-day combination antibiotic therapy using oral rifampin (40 mg/kg, twice daily) plus oral azithromycin (50 mg/kg, once per day), oral clarithromycin (80 mg/kg, twice daily), or parenteral nafcillin (30 mg/kg, four times dai ly). The left tibial metaphysis of New Zealand White rabbits was infected w ith Staphylococcus aureus, Grades 3 to 4 osteomyelitis (according to the Ci erny-Mader classification system) development in the rabbits was confirmed radiographically, After antibiotic therapy regimens of 28 days, all tibias from controls that were infected but left untreated (n = 10) revealed posit ive cultures for Staphylococcus aureus at a mean concentration of 2.8 x 10( 4) colony forming units/g bone. The rifampin plus clarithromycin (n = 15) a nd rifampin plus azithromycin (n = 15) groups showed significantly lower pe rcentages of positive Staphylococcus aureus infection (20% and 13.3%, respe ctively) and bacterial concentrations (3.5 x 10(1) and 1.75 x 10(1) colony forming units/g bone, respectively). The osteomyelitic tibias of the nafcil lin plus rifampin treated group (n = 7) showed no detectable Staphylococcus aureus infection (significantly lower than controls). The differences obse rved for bone bacterial concentrations and sterilization percentages betwee n the antibiotic treated groups were not statistically significant. Althoug h fluoroquinolones (including ofloxacin and ciprofloxacin) are the agents u sually prescribed with rifampin, increasing resistance has been observed. A lthough macrolides traditionally are not used in the treatment of osteomyel itis, the results of this study indicate that azithromycin and clarithromyc in may be attractive partners for rifampin for the treatment of Staphylococ cus aureus osteomyelitis in humans.