title: In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004.
abstract: Ketolides, 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 [MIC90S], 0.25 to 4 micrograms/ml), penicillin-resistant pneumococci (MIC90, 0.25 micrograms/ml), and most beta-hemolytic streptococci. All Streptococcus pneumoniae and beta-hemolytic streptococcus strain were inhibited by ketolide concentrations of < or = 0.25 micrograms/ml. Against 165 erythromycin-resistant strains, RU-64004 inhibited (MICs, < or = 0.5 micrograms/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 (MIC50S, 0.03 to 2 micrograms/ml). The ketolide was also active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 micrograms/ml), pathogenic Neisseria spp. (MIC90, 0.5 micrograms/ml), and many gram-positive anaerobes (MIC90, 0.5 micrograms/ml). RU-64004 may enhance the role of macrolide drugs in the treatment of some serious infections caused by MLS-resistant gram-positive organisms.
authors.affiliation: Department of Pharmaceutical Care, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jamjian
authors.forename: D J
authors.initials: DJ
authors.lastname: Biedenbach
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D016983:Enterococcus / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D048628:Ketolides; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D013210:Staphylococcus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; C105420:RU 64004