ABBANAT D, WEBB G, ASHLEY G, FOLENO B, FU H, LI Y, LICARI P, MACIELAG M, MONTENEGRO D, WIRA E, BUSH K; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. F-1663.

Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ.

BACKGROUND: Ketolides are a new class of semisynthetic macrolide antibiotics active against many macrolide-sensitive and -resistant Gram-positive bacteria. JNJ-17155437 and JNJ-17155528 are 2-fluoro, 6-O-naphthyridinylpropenyl ketolides prepared synthetically from 15-methylerythromycin A, produced in genetically modified strains. Because reports have varied concerning the bacteriostatic nature of telithromycin, MIC values and time-kill kinetics of telithromycin and the naphthyridine-containing ketolides were compared using selected pneumococcal strains. METHODS: MICs were determined against 70 Gram-negative and Gram-positive isolates using NCCLS methods. Time-kill studies were conducted according to NCCLS. Effects on protein synthesis were measured using an in vitro coupled transcription-translation assay. RESULTS: MIC[90] values for telithromycin, JNJ-17155437 and JNJ-17155528 were 0.5, 0.25 and 0.25 microg/ml, respectively, against macrolide-susceptible and -resistant (mef, erm) pneumococci, and selected macrolide-susceptible and -resistant (msr and inducible erm-containing) staphylococci. MIC[90] values for JNJ-17155437, JNJ-17155528 and telithromycin against H. influenzae strains were 2 microg/ml. Telithromycin and JNJ-17155437 were bacteriostatic toward 2 macrolide-susceptible S. pneumoniae strains, and slowly bactericidal toward 2 macrolide-resistant erm- and mef-containing S. pneumoniae strains. IC[50] values for the 3 ketolides in the coupled transcription-translation assay system were 0.2 - 0.3 microM. CONCLUSIONS: JNJ-17155437 and JNJ-17155528 had MIC[90] values equal to or 2-fold lower than those of telithromycin against H. influenzae, and macrolide-susceptible and -resistant Gram-positive cocci. Time-kill kinetics for JNJ-17155437 were similar to those for telithromycin against the pneumococcal strains.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Bacterial Agents
• Clindamycin
• Haemophilus influenzae
• Heterocyclic Compounds
• In Vitro
• Ketolides
• Microbial Sensitivity Tests
• Naphthyridines
• Ofloxacin
• Staphylococcus
• Streptococcus pneumoniae
• telithromycin

Other ID:

• GWAIDS0028160

UI: 102267784

From Meeting Abstracts