In vitro and in vivo antibacterial activities of BMY 40062, a new fluoronaphthyridone.

Abstract

The in vitro and in vivo activities of a new naphthyridone, BMY 40062, were compared with those of ciprofloxacin and ofloxacin. BMY 40062 showed about threefold more activity than ciprofloxacin showed and four- to eightfold more activity than ofloxacin showed against staphylococci, streptococci, and enterococci. BMY 40062 showed generally twofold less activity than ciprofloxacin showed against most species of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. but twofold more activity than ofloxacin showed against these organisms. BMY 40062 and ofloxacin were more active than ciprofloxacin against Bacteroides fragilis and Clostridium difficile. The antiureaplasmal and antichlamydial activities of BMY 40062 were similar to those of the tetracyclines and were 4- and 16-fold, respectively, higher than those of ciprofloxacin. The in vitro activities of BMY 40062 were influenced by pH and magnesium, although these factors appeared to affect the activity of BMY 40062 against P. aeruginosa to a lesser extent than those of ciprofloxacin and ofloxacin. BMY 40062 was found to be bactericidal, and cross-resistance with other fluoroquinolones was observed. In mouse protection tests, the efficacy of BMY 40062 reflected its in vitro potency. BMY 40062 exhibited longer half-life, higher maximum concentration in serum, greater area under the curve, and better bioavailability in mice after oral dosing than ciprofloxacin. Compared with ofloxacin, BMY 40062 had a lower maximum concentration in serum but a much longer half-life in mice. BMY 40062 was more effective than ciprofloxacin and ofloxacin in penetrating mouse macrophages and killing macrophage-associated Staphylococcus aureus.