ANTIPNEUMOCOCCAL ACTIVITIES OF RP-59500 (QUINUPRISTIN-DALFOPRISTIN), PENICILLIN-G, ERYTHROMYCIN, AND SPARFLOXACIN DETERMINED BY MIC AND RAPID TIME-KILL METHODOLOGIES
Ga. Pankuch et al., ANTIPNEUMOCOCCAL ACTIVITIES OF RP-59500 (QUINUPRISTIN-DALFOPRISTIN), PENICILLIN-G, ERYTHROMYCIN, AND SPARFLOXACIN DETERMINED BY MIC AND RAPID TIME-KILL METHODOLOGIES, Antimicrobial agents and chemotherapy, 40(7), 1996, pp. 1653-1656
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.