ANTIPNEUMOCOCCAL ACTIVITIES OF RP-59500 (QUINUPRISTIN-DALFOPRISTIN), PENICILLIN-G, ERYTHROMYCIN, AND SPARFLOXACIN DETERMINED BY MIC AND RAPID TIME-KILL METHODOLOGIES

Previous time-kill studies have shown that RP 59500 is rapidly bacteri cidal against pneumococci. To extend these findings, the activities of RP 59500, its two components RP 57669 and RP 54476, penicillin G, ery thromycin, and sparfloxacin against 26 penicillin-susceptible, 25 peni cillin-intermediate, and 25 penicillin-resistant pneumococci were dete rmined by the agar dilution MIC and the time-kill testing methodologie s within 10 min (ca. 0.2 h) and at 1 and 2 h. Respective agar dilution MICs at which 90% of isolates are inhibited for penicillin-susceptibl e, -intermediate, and -resistant strains were as follows: penicillin G , 0.03, 1, and 4 mu g/ml; RP 59500, 1, 1, and 1 mu g/ml; RP 57669, 8, 32, and 16 mu g/ml; RP 54476, > 128, > 128, and > 128 mu g/ml; erythro mycin, 0.06, 2, and > 128 mu g/ml; and sparfloxacin, 1, 0.5, and 0.5 m u g/ml. RP 59500 was equally active (MIC at which 90% of isolates are inhibited, 1.0 mu g/ml) against erythromycin-susceptible and -resistan t strains. Time-kill testing results showed that only RP 59500 at one to four times the MIC killed pneumococci at 0.2 h; RP 59500 was also t he most active compound at 1 and 2 h. By comparison, penicillin and sp arfloxacin at one, two, and four times the MICs reduced the original i noculum by greater than or equal to 1 log at 2 h for 46, 80, and 95% a nd for 50, 72, and 86% of strains, respectively. The killing activity of RP 59500 was the same against erythromycin-susceptible and -resista nt strains. RP 57669, RP 54476, and erythromycin were either inactive or bacteriostatic at 2 h. Of all drugs tested, RP 59500 yielded the mo st rapid killing.