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

Abstract

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 itjection 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.

Comparative evaluation of cefazolin and clindamycin in the treatment of experimental Staphylococcus aureus osteomyelitis in rabbits

“…In patients who are not allergic to penicillin, semisynthetic penicillins are the antibiotics of choice. In a previous study, using the same rabbit model and strain of S. aureus (14), nafcillin sterilized 12 of 20 tibias (60%). Thus, in the same model nafcillin was similar to cefazolin in the treatment of S. aureus osteomyelitis.…”

In Vivo Expression of Streptococcus pyogenes Immunogenic Proteins during Tibial Foreign Body Infection

“…Briefly, an 18-gauge needle was inserted into the intramedullary cavity of the left tibial metaphysis. A 0.1-ml volume of a 5% (wt/vol) solution of sodium morrhuate (Eli Lilly, Indianapolis, IN), 0.1 ml of the GAS mixture (ϳ2 ϫ 10 7 CFU), and 0.2 ml of sterile saline solution were injected sequentially (25)(26)(27)(28)(29). Serum was collected prior to inoculation and at 28 days postinoculation.…”

Use of Quinolones for the Treatment of Osteomyelitis and Septic Arthritis

“…An ex- Another aspect to be discussed is whether the quinolones are active under the stringent physicochemical conditions of a focus of osteomyelitis or arthritis, characterized by a low pH [6] and low Po, [7]. Kill curves for difloxacin and A56620, determined under aerobic (100mm Hg) and anaerobic (10mm Hg) conditions have shown both antibiotics to be equally effective under both conditions [8]. Lowering of the pH dramatically increased the MIC of some, but not all, quinolones [9], a finding that suggests the influence of pH should be explored for each individual quinolone.…”