title: Antimicrobial activity of RU-66647, a new ketolide.
abstract: A new macrolide subclass called ketolides, possess a mode of action similar to the macrolide-lincosamide-streptogramin (MLS) compounds. Utilizing reference in vitro tests, the in vitro activity of RU-66647 (a ketolide) was compared to other MLS compounds against 376 Gram-positive organisms and over 400 representative strains of Gram-negative bacilli. The ketolide's spectrum was most similar to clindamycin and an earlier drug in the series (RU-64004 or RU-004) against staphylococci and streptococci. However, RU-66647 was more active than erythromycin and azithromycin against oxacillin-resistant Staphylococcus spp. and vancomycin-resistant enterococci. Ketolide activity was more potent than other MLS drugs against vancomycin-susceptible enterococci (MIC90, 0.25-4 micrograms/ml) and all streptococci (MICs, < or = 0.25 microgram/ml). Erythromycin-resistant (constitutive) strains were generally inhibited by < or = 2 micrograms RU-66647/ml (staphylococci, 31 to 36%; streptococci, 100%; enterococci, 72%). RU-66647 was active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 microgram/ml), and pathogenic Neisseria spp. (MIC90 0.5 microgram/ml). The ketolide failed to inhibit Enterobacteriaceae, nonfermentative Gram-negative bacilli, and Bacteriodes fragilis group strains. RU-66647 was observed to be a promising new compound directed toward some organisms resistant to other MLS-class drugs.
authors.affiliation: Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: D J
authors.initials: DJ
authors.lastname: Biedenbach
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D001421:Bacteria, Anaerobic / Q000187:drug effects; D002981:Clindamycin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D048628:Ketolides; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D013210:Staphylococcus / Q000187:drug effects / Q000378:metabolism; D013291:Streptococcus / Q000187:drug effects / Q000378:metabolism; D014769:Virginiamycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; C105420:RU 64004; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D002981:Clindamycin; D004917:Erythromycin; D017963:Azithromycin; C106791:telithromycin