IN-VITRO EVALUATION OF A NOVEL KETOLIDE ANTIMICROBIAL AGENT, RU-64004

Eietolides, a novel macrolide subclass, possess a mode of action that is similar to that of structurally related macrolide-lincosamide-strep togramin (MLS) compounds. By using reference in vitro tests, the in vi tro activity of RU-64004 was compared to those of six other MLS compou nds against more than 800 clinical pathogens, including 356 gram-posit ive organisms. The spectrum of activity of the ketolide was most simil ar to that of clindamycin versus staphylococci and streptococci and su perior to those of all macrolides tested against oxacillin-resistant s taphylococci and vancomycin-resistant (vanA, vanB, and vanC) enterococ cal isolates. The activity of the ketolide was greater than those of t he macrolides, azalides, or clindamycin tested against vancomycin-susc eptible 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. Agains t 165 erythromycin-resistant strains, RU-64004 inhibited (MICs, less t han 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 ag ainst all tested isolates with the exception of non-Enterococcus faeci um enterococci, against which the ketolide exhibited greater potency ( MIC(50)s, 0.03 to 2 mu g/ml). The ketolide was also active against Hae mophilus influenzae (MIC(90), 2 mu g/ml), Moraxella catarrhalis (MIG(9 0), 0.12 mu g/ml), pathogenic Neisseria spp. (MIC(90), 0.5 mu g/ml), a nd many gram-positive anaerobes (MIC(90), 0.5 mu g/ml). RU-64004 may e nhance the role of macrolide drugs in the treatment of some serious in fections caused by MLS-resistant gram-positive organisms.