Comparative evaluation of A-56619, A-56620, and nafcillin in the treatment of experimental Staphylococcus aureus osteomyelitis.

A rabbit model for Staphylococcus aureus osteomyelitis was used to compare the results of treatment with A-56619 and A-56620, two new aryl-fluoroquinolones, and nafcillin. A-56619 (15 mg/kg) and A-56620 (20 mg/kg), both used for 28 days of treatment, were injected subcutaneously every 12 h, and nafcillin (40 mg/kg) was injected every 6 h. After treatment, S. aureus was found on bone marrow cultures from 19 of 20 control rabbits, 6 of 20 treated with A-56619, 14 of 20 treated with A-56620, and 8 of 20 treated with nafcillin. Drug concentrations in serum and uninfected and infected bone were measured 1 h after A-56619 and A-56620 injection and 30 min after nafcillin injection in a group of rabbits that had been infected for 3 to 4 weeks. The concentrations in infected bone were similar for all three drugs and were significantly higher than in uninfected bone. The results of this study showed that A-56619 had a high rate of eradication of S. aureus from infected bone and compared favorably to nafcillin.

Effect of hyperbaric oxygen on the blood: cerebrospinal fluid transfer of tobramycin.

The blood:cerebrospinal fluid (CSF) transfer of the aminoglycoside antibiotic, tobramycin (TOB) was assessed in rabbits. The CSF:blood ratio of TOB, 90 min after a subcutaneous injection, was approximately 1:100 as measured by an agar disc diffusion bioassay. Hyperbaric oxygen therapy at a pressure of 3 ATA caused a slight, non-significant, increase in this ratio, while high dose carbon dioxide, a treatment known to damage the blood:brain barrier, more than doubled this ratio. Thus, hyperbaric oxygen has no significant effect on CSF concentration of TOB in rabbits with intact meninges.