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Antimicrobial Agents and Chemotherapy, 02 1997, 454-459, Vol 41, No. 2
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004

C Jamjian, DJ Biedenbach and RN Jones
Department of Pharmaceutical Care, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.

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.


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