The in vitro activities of two new
ketolides,
HMR 3647 and
HMR 3004, were tested by the
agar dilution method against 280 strains of gram-positive bacteria with different
antibiotic susceptibility profiles, including Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen
erythromycin-susceptible (EMs),
methicillin-susceptible S. aureus strains were found to have
HMR 3647 and
HMR 3004 MICs 4- to 16-fold lower than those of
erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [
HMR 3647 and
HMR 3004], 0.03 microgram/ml; range, 0.03 to 0.06 microgram/ml; MIC50 [
erythromycin], 0.25 microgram/ml; range, 0.25 to 0.5 microgram/ml). All methicillin-resistant S. aureus strains tested were resistant to
erythromycin and had
HMR 3647 and
HMR 3004 MICs of > 64 micrograms/ml. The
ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with
erythromycin susceptibility. The MIC50s of
HMR 3647 and
HMR 3004 against Ems enterococci (MIC < or = 0.5 microgram/ml) and those enterococcal isolates with
erythromycin MICs of 1 to 16 micrograms/ml were 0.015 microgram/ml. E. faecalis strains that had
erythromycin MICs of 128 to > 512 micrograms/ml showed
HMR 3647 MICs in the range of 0.03 to 16 micrograms/ml and
HMR 3004 MICs in the range of 0.03 to 64 micrograms/ml. In the group of E. faecium strains for which MICs of
erythromycin were > or = 512 micrograms/ml, MICs of both
ketolides were in the range of 1 to 64 micrograms/ml, with almost all isolates showing ketolide MICs of < or = 16 micrograms/ml. The
ketolides were also more active than
erythromycin against group A streptococci, group B streptococci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of
ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against
infections caused by these bacteria is warranted.