Treatment of experimental staphylococcal osteomyelitis with rifampin and trimethoprim, alone and in combination.

Rifampin and trimethoprim were used alone and in combination in the treatment of chronic osteomyelitis due to Staphylococcus aureus in rabbits. Rifampicin levels in infected bone were well above the minimum inhibitory concentration of the infecting strain of S. aureus for at least 4 h after injection. In contrast, trimethoprim levels in diseased bone were below the minimum inhibitory concentration as early as 1 h after injection. Trimethoprim or rifampin, administered alone for 14 days, were ineffective in sterilizing infected rabbit bones. The combination of rifampin plus trimethoprim was significantly more effective (P less than 0.005) than either agents given alone for a comparable duration of time. Staphylococci isolated from the bones of rabbits treated with rifampin alone or rifampin plus trimethoprim were uniformly resistant to rifampin, but retained their susceptibility to trimethoprim.

Experimental osteomyelitis caused by Pseudomonas aeruginosa.

An experimental model of chronic osteomyelitis caused by Pseudomonas aeruginosa was established with use of techniques identical to those employed previously with Staphylococcus. Infection of bone was consistently produced, but the disease was less severe than that seen with Staphylococcus. There were lower mortality, decreased severity of infection as demonstrated by X ray, and less evidence of sequestrum formation with P. aeruginosa than with Staphylococcus. Carbenicillin was used alone and in combination with sisomicin in the treatment of experimental pseudomonas osteomyelitis. The combination, when administered for four weeks, was significantly more effective than either agent alone.