In vitro activity of CI-919 (AT-2266), an oral antipseudomonal compound

Abstract

We tested CI-919 (AT-2266), a nalidixic acid analog, against 555 gram-positive and gram-negative bacteria, using microbroth or agar dilution methods. The activity of CI-919 was compared with those of cephalosporins, tobramycin, ticarcillin, dicloxacillin, rifampin, chloramphenicol, ampicillin, and trimethoprimsulfamethoxazole. The minimal inhibitory concentrations of CI-919 for 90% of isolates were (in micrograms per milliliter): Pseudomonas spp. (including Pseudomonas aeruginosa), 4.0; Enterobacteriaceae, 0.5; Staphylococcus spp., 2.0; Haemophilus influenzae, 0.12; Campylobacter jejuni, 0.12; and enterococci, 16. The minimal inhibitory concentrations of CI-919 for 90% of 82 tobramycin-resistant, gram-negative strains was 4.0 micrograms/ml. CI-919 was bactericidal for most isolates, showing no cross-resistance with unrelated antimicrobial agents, and was stable for 11 weeks at temperatures ranging from 22 to -70 degrees C. Inoculum size and media pH had little effect on the antibacterial activity of CI-919 for nine strains tested. CI-919 may be useful as an oral antibiotic for the treatment of infections due to diverse bacteria, including P. aeruginosa.