Susceptibility of penicillin-susceptible and -resistant pneumococci to dirithromycin compared with susceptibilities to erythromycin, azithromycin, clarithromycin, roxithromycin, and clindamycin

Abstract

Agar dilution with incubation in air and CO2 was used to determine the MICs of erythromycin, dirithromycin, azithromycin, clarithromycin, roxithromycin, and clindamycin for 79 penicillin-susceptible, 72 penicillin- intermediate, and 74 penicillin-resistant pneumococci (158 erythromycin- susceptible and 67 erythromycin-resistant pneumococci). MICs obtained in air were usually 1 to 3 dilutions lower than those obtained in CO2. In air, the respective MICs at which 50% (MIC50s) find 90% (MIC90s) of penicillin- susceptible, -intermediate, and -resistant strains are inhibited were as follows: erythromycin, 0.016 and 0.5, 0.03 and >64, and 2 and >64 μg/ml; dirithromycin, 0.03 and 0.5, 0.06 and >64, and 8 and >64 μg/ml; azithromycin, 0.03 and 0.5, 0.06 and >64 and 2 and >64 μg/ml; clarithromycin, 0.016 and 0.06; 0.03 and >64 and 2 and >64 μg/ml; roxithromycin, 0.06 and 2, 0.06 and >64, and 2 and >64 μg/ml; and c clindamycin, 0.03 and 0.06, 0.06 and >64, and 0.06 and >64 μg/ml. The MICs of erythromycin, azithromycin, and dirithromycin were very similar; however, clarithromycin MICs were generally 1 to 2 dilutions lower and roxithromycin MICS were 1 to 2 dilutions higher than those of the other compounds tested. Strains resistant to one macrolide were resistant to all macrolides; however, not all macrolide-resistant strains were resistant to clindamycin, and 32 macrolide-resistant (MICs, ≤128 μg/ml), clindamycin-susceptible (MICs, ≤0.25 μg/ml) strains were encountered. Time-kill testing of six strains showed similar killing kinetics for all compounds, with 99.9% killing of all strains observed with the compounds only at or above the MIC after 24 h.