In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria

The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were t ested by the agar dilution method against 280 strains of gram-positive bact eria with different antibiotic susceptibility profiles, including Staphyloc occus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus sp p, (group A streptococci, group B streptococci, Streptococcus pneumoniae, a nd alpha-hemolytic streptococci), Seventeen erythromycin-susceptible (Em(s) ), methicillin-susceptible S. aureus strains were found to have HMR 3647 an d HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at whic h 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 mu g /ml; range, 0.03 to 0.06 mu g/ml; MIC50 [erythromycin], 0.25 mu g/ml; range , 0.25 to 0.5 mu g/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of > 64 m u g/ml. The ketolides were slightly more active against E. faecalis than ag ainst E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC(50)s of HMR 3647 and HMR 3004 against Em(s) enteroc occi (MIC less than or equal to 0.5 mu g/ml) and those enterococcal isolate s with erythromycin MICs of 1 to 16 mu giml were 0.015 mu g/ml. E. faecalis strains that had erythromycin MICs of 128 to >512 mu g/ml showed HMR 3647 MICs in the range of 0.03 to 16 mu g/ml and HMR 3004 MICs in the range of 0 .03 to 64 mu g/ml, In the group of E. faecium strains for which MICs of ery thromycin were greater than or equal to 512 mu g/ml, MICs of both ketolides were in the range of 1 to 64 mu g/ml, with almost all isolates showing ket olide MICs of less than or equal to 16 mu g/ml, The ketolides were also mor e active than erythromycin against group A streptococci, group B streptococ ci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids, Time-kill studies showed bactericidal activity against one st rain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of the se agents for possible efficacy against infections caused by these bacteria is warranted.