MIC and time-kill study of antipneumococcal activities of RPR 106972 (a new oral streptogramin), RP 59500 (quinupristin-dalfopristin), pyostacine (RP 7293), penicillin G, cefotaxime, erythromycin, and clarithromycin against 10 penicillin-susceptible and -resistant pneumococci.
Broth MICs and time-kill studies were used to test the activity of RP 59500 (quinupristin-dalfopristin), RPR 106972, pyostacine (RP 7293), erythromycin, clarithromycin, and cefotaxime for four penicillin-susceptible (MICs of 0.008 to 0.03 microgram/ml), two penicillin-intermediate (MIC of 0.25 microgram/ml), and four penicillin-resistant (MIC of 2.0 to 4.0 micrograms/ml) strains of pneumococci: 6 of 10 strains were resistant to macrolides (MICs of > or = 0.5 microgram/ml). MICs of RP 59500 (0.5 to 1.0 microgram/ml), RPR 106972 (0.125 to 0.25 microgram/ml), and pyostacine (0.125 to 0.25 microgram/ml) did not alter with the strain's penicillin or macrolide susceptibility status. Three penicillin-susceptible strains and one penicillin-intermediate strain were susceptible to macrolides (MICs of < or = 0.25 microgram/ml); the macrolide MICs for the remaining strains were > or = 4.0 micrograms/ml. Cefotaxime MICs rose with those of penicillin G, but all strains were inhibited at MICs of < or = 2.0 micrograms/ml. RP 59500 was bactericidal for all strains after 24 h at 2 x MIC and yielded 90% killing of all strains at 6 h at 2 x MIC; at 8 x MIC, RP 59500 showed 90% killing of six strains within 10 min (approximately 0.2 h). In comparison, RPR 106972 was bactericidal for 9 of 10 strains at 2 x MIC after 24 h and yielded 90% killing of all strains at 2 x MIC after 6 h; 90% killing of six strains was found at 8 x MIC at 0.2 h. Results for pyostacine were similar to those of RPR 106972. Erythromycin and clarithromycin were bactericidal for three of four macrolide-susceptible strains after 24 h at 4 x MIC. Clarithromycin yielded 90% killing of three strains at 8 x MIC after 12 h. Cefotaxime was bactericidal for all strains after 24 h at 4 x MIC, yielding 90% killing of all strains after 6 h at 4 x MIC. All three streptogramins yielded rapid killing of penicillin- and erythromycin-susceptible and -resistant pneumococci and were the only compounds which killed significant numbers of strains at 0.2 h.
Pankuch
G A
GA
Department of Pathology (Clinical Microbiology), Hershey Medical Center, Pennsylvania 17033, USA.
Jacobs
M R
MR
Appelbaum
P C
PC
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D004917:Erythromycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000494:pharmacology; D010403:Penicillin Resistance; D010406:Penicillins / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013997:Time Factors; D014769:Virginiamycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins; C099364:RPR 106972; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D004917:Erythromycin; D017291:Clarithromycin; D002439:Cefotaxime; D010400:Penicillin G