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.