IN-VITRO ACTIVITY OF THE NEW FLUOROQUINOLONE CP-99,219

The in vitro activity of the new fluoroquinolone CP-99,219 {7-(3-azabi cyclo[3.1.0]hexyl)naphthyridone} was compared with those of four other quinolones against 541 gram-negative, 283 gram-positive, and 70 anaer obic bacterial isolates. CP-99,219 inhibited 90% of many isolates in t he family Enterobacteriaceae at a concentration of less than or equal to 0.25 mu g/ml (range, <0.008 to 1 mu g/ml), an activity comparable t o those of tosufloxacin and sparfloxacin and two times greater than th at of temafloxacin. Ninety percent of the Proteus vulgaris, Providenci a rettgeri, Providencia stuartii, and Serratia marcescens isolates wer e inhibited by 0.5 to 2 mu g of CP-99,219 per ml. CP-99,219 inhibited 90% of the Pseudomonas aeruginosa and Haemophilus influenzae isolates at 1 and 0.015 mu g/ml, respectively. The compound inhibited methicill in-susceptible Staphylococcus aureus at 0.06 mu g/ml, whereas a ciprof loxacin concentration of 1 mu g/ml was required to inhibit these organ isms. CP-99,219 inhibited 90% of methicillin-resistant S. aureus isola tes at a concentration of less than or equal to 4 mu g/ml, while cipro floxacin and temafloxacin had MICs against these isolates of >16 mu g/ ml. Streptococci were inhibited by less than or similar to 0.25 mu g/m l, an activity comparable to that of tosufloxacin. CP-99,219 was eight times more active than ciprofloxacin against Streptococcus pneumoniae . Bacteroides species were inhibited by CP-99,219 at a concentration o f 2 mu g/ml, whereas inhibition of these species required 4- and 16-mu g/ml concentrations of tosufloxacin and ciprofloxacin, respectively. The MBCs of CP-99,219 ranged from two to four times the MICs, and inoc ulum-size had a minimal effect on MIC. CP-99,219 was active against P. aeruginosa at pH 5.5, with only a fourfold increase in MIC compared w ith values obtained at pH 7.5. The addition of up to 9 mM Mg2+ increas ed the MIC range from 0.03 to 0.06 mu g/ml to 0.12 to 0.5 mu g/ml. In view of its excellent in vitro activity against both gram-positive and gram-negative bacteria, CP-99,219 merits further study to determine i ts clinical pharmacologic properties and potential for therapeutic use .