Activities of tobramycin and azlocillin alone and in combination against experimental osteomyelitis caused by Pseudomonas aeruginosa

Azlocillin and tobramycin were used alone and in combination in the treatment of chronic osteomyelitis due to Pseudomonas aeruginosa in rabbits. This combination showed in vitro synergy measured by both the checkerboard technique and time-kill curves. A marked inoculum effect was demonstrated in vitro with azlocillin and the infecting strain of P. aeruginosa. The minimal inhibitory concentration of azlocillin, with an inoculum of 10(5) organisms, was 12.5 micrograms/ml; when the inoculum size was increased to 10(7) organisms, the minimal inhibitory concentration rose to more than 500 micrograms/ml. In therapeutic trials, the combination of azlocillin and tobramycin, given for 28 days, was significantly better than either no therapy or azlocillin alone, but was not significantly better than tobramycin alone. Even after 4 weeks of combined therapy with azlocillin and tobramycin, P. aeruginosa was recovered from the bones of 60% of the treated rabbits.