Eietolides, a novel macrolide subclass, possess a mode of action that is similar to that of structurally related macrolide-lincosamide-streptogramin (MLS) compounds. By using reference in vitro tests, the in vitro activity of RU-64004 was compared to those of six other MLS compounds against more than 800 clinical pathogens, including 356 gram-positive organisms. The spectrum of activity of the ketolide was most similar to that of clindamycin versus staphylococci and streptococci and superior to those of all macrolides tested against oxacillin-resistant staphylococci and vancomycin-resistant (vanA, vanB, and vanC) enterococcal isolates. The activity of the ketolide was greater than those of the macrolides, azalides, or clindamycin tested against vancomycin-susceptible enterococci (MICs at which 90% of isolates are inhibited [MIC(90)s], 0.25 to 4 mu g/ml), penicillin-resistant pneumococci (MIC(90), 0.25 mu g/ml), and most beta-hemolytic streptococci. All Streptococcus pneumoniae and beta-hemolytic streptococcus strains were inhibited by ketolide concentrations of less than or equal to 0.25 mu g/ml. Against 165 erythromycin-resistant strains, RU-64004 inhibited (MICs, less than or equal to 0.5 mu g/ml) approximately one-third of staphylococci, all streptococci, and slightly more than one-half of the enterococci. Quinupristin-dalfopristin (a streptogramin combination) was active against all tested isolates with the exception of non-Enterococcus faecium enterococci, against which the ketolide exhibited greater potency (MIC(50)s, 0.03 to 2 mu g/ml). The ketolide was also active against Haemophilus influenzae (MIC(90), 2 mu g/ml), Moraxella catarrhalis (MIG(90), 0.12 mu g/ml), pathogenic Neisseria spp. (MIC(90), 0.5 mu g/ml), and many gram-positive anaerobes (MIC(90), 0.5 mu g/ml). RU-64004 may enhance the role of macrolide drugs in the treatment of some serious infections caused by MLS-resistant gram-positive organisms.
