Study of comparative antipneumococcal activities of penicillin G, RP 59500, erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill methodology

Abstract

Time-kill studies were used to examine the in vitro activities of penicillin G, RP 59500, erythromycin, ciprofloxacin, sparfloxacin, and vancomycin against 10 pneumococci expressing various degrees of susceptibility to penicillin and erythromycin. RP 59500 MICs for all strains were 0.5 to 2.0 micrograms/ml, while erythromycin MICs were 0.008 to 0.06 microgram/ml for erythromycin-susceptible strains and 32.0 to 64.0 micrograms/ml for erythromycin-resistant strains. Strains were more susceptible to sparfloxacin (0.125 to 0.5 microgram/ml) than to ciprofloxacin (0.5 to 4.0 micrograms/ml), and all were inhibited by vancomycin at MICs of 0.25 to 0.5 microgram/ml. Time-kill studies showed that antibiotic concentrations greater than the MIC were bactericidal for each strain, with the following exceptions. Erythromycin was bactericidal for one penicillin-resistant strain at 6 h, with regrowth after 12 and 24 h. Three penicillin-susceptible strains were bacteriostatically inhibited by erythromycin at concentrations greater than or equal to the MIC by 6 h. One penicillin-susceptible strain (penicillin MIC, 0.06 microgram/ml) was bacteriostatically inhibited by penicillin G at 24 h at the MIC or at one-half the MIC; a bactericidal effect was found only with penicillin G at concentrations of > or = 0.25 microgram/ml. At 10 min after inoculation a 1- to 3-log10-unit reduction (90 to 99.9%) in the original inoculum was seen for 6 of 10 strains with RP 59500 at concentrations greater than or equal to the MIC. This effect was not found with any of the other compounds tested. A bactericidal effect was found at > or = 6 h with RP 59500 at concentrations of one-half to one-quarter the MIC in 7 of 10 strains, and a bacteriostatic effect was found in 3 or 10 strains, with regrowth at 24 h. One penicillin-resistant strain was examined by the time-kill methodology at 0, 1, 2, and 3 h. RP 59500 at a concentration equal to the MIC was bactericidal within 1 h, and at a concentration of one-half the MIC it was bactericidal within 3 h. This phenomenon was not seen with the other antimicrobial agents tested. Regrowth of strains at ciprofloxacin concentrations equal to the MIC or at a one-half to one-quarter the MIC was found. For sparfloxacin, three of the four penicillin-susceptible strains and two of four penicillin-resistant strains were bacteriostatically inhibited by 6 h. Bactericidal effects were found at 6, 12, and 24 h with both intermediate-resistant, one penicillin-susceptible, and two penicillin-resistant strains. Complete killing was observed with vancomycin at concentrations greater than MIC. Of the new compounds tested, RP 59500 and sparfloxacin show promise for the treatment of infections caused by penicillin-susceptible and -resistant pneumococci. The clinical significance of rapid killing by RP 59500 remains to be determined.