Experimental osteomyelitis. V. Therapeutic trials with oxacillin and sisomicin alone and in combination

Oxacillin was used alone and in combination with sisomicin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Within diseased bone, levels of oxacillin and sisomicin remained higher than the minimal inhibitory concentration for 2 and 6 hr, respectively, after injection of 50 mg of oxacillin/kg and 10 mg of sisomicin/kg. Treatment with 50 mg of oxacillin/kg four times daily or 50 mg/kg every 4 hr around the clock for 28 days sterilized 30% of the rabbit bones. Sisomicin (10 mg/kg) injected twice daily for 28 days sterilized only 5% of the rabbit bones. In contrast, treatment with the combination of oxacillin and sisomicin for either 14 or 28 days was significantly more effective, sterilizing 78% and 85%, respectively, of the bones of treated animals. S. Aureus isolated from bones of animals treated with sisomicin alone contained aminoglycoside-resistant microcolonies. Resistant microcolonies were not recovered from animals treated with oxacillin or with the combination of oxacillin plus sisomicin. In vitro studies of bacterial killing by each antibiotic alone and in combination showed more bacterial killing with the combination than with either agent alone; in vitro the combination prevented emergence of resistant microcolonies. Combination antibiotic therapy appears to be more effective in treatment of experimental osteomyelitis due to S. aureus than therapy with a single agent.