Experimental Chronic Staphylococcal Osteomyelitis in Rabbits: Treatment with Rifampin Alone and in Combination with Other Antimicrobial Agents

The efficacy of rifámpin alone and in combination with sisomicin, cephalothin, sisomicin and cephalothin, or trimethoprim was measured in an experimental model of chronic osteomyelitis due to Staphylococcus aureus in rabbits. Single-drug regimens used for 28 days were relatively ineffective (bone sterilization rate, 5%-55%). Combinations of rifampin with other agents were more effective (bone sterilization rate, 75%-100%). The combination of rifampin, sisomicin, and cephalothin given for only 14 days sterilized the bones of all treated rabbits. Staphylococci isolated from the bones of rabbits that had received rifampin alone or in combination with other antibiotics were highly resistant to rifampin; in contrast, these organisms remained sensitive to the other agents used. Results of in vitro studies of synergy correlated with in vivo results in some but not all instances. The results obtained with rifampin in the treatment of experimental chronic osteomyelitis caused by S. aureus suggest that clinical trials of this agent for the treatment of osteomyelitis in humans are warranted.