ABBANAT DR, ASHLEY G, FOLENO B, FU H, HILLIARD J, LI Y, LICARI P, MACIELAG M, MELTON J, RAINA D, STRYKER S, WIRA E, BUSH K; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. F-1203.

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

BACKGROUND: Ketolides are semisynthetic macrolide antibiotics effective against macrolide-susceptible and -resistant respiratory tract infections. JNJ-17156581 and JNJ-17156815 are 2-fluoro-6-O-3-(biheteroaryl)-2-propenyl ketolides prepared synthetically from 15-methylerythromycin A, produced in genetically modified strains. METHODS: MIC values were determined against 105 Gram-negative and Gram-positive isolates, including macrolide-susceptible and -resistant S. pneumoniae and S. pyogenes strains, using NCCLS methods. In vivo efficacy was determined in a murine S. aureus systemic lethal infection model. RESULTS: The MIC[90] value for telithromycin, JNJ-17156581 and JNJ-17156815 against 10 erm-containing pneumococci was 0.06 microg/ml, while MIC[90] values against 10 mef-containing pneumococci; were 0.25, 0.12 and 0.12 microg/ml, respectively. MIC values for telithromycin, JNJ-17156581 and JNJ-17156815 were 8, 1 and 1 microg/ml, respectively, against an erm(B)-containing S. pyogenes strain. MIC[90] values for telithromycin, JNJ-17156581 and JNJ-17156815 against 12 H. influenzae strains were 4, 8 and 4 microg/ml, respectively. In vivo ED[50] values for telithromycin, JNJ-17156581 and JNJ-17156815 were 4.3, 1.4 and 2.0 mg/kg, respectively, when dosed s.c., and 24, 3.5 and 11 mg/kg, respectively, when dosed p.o. in a murine S. aureus systemic lethal infection model. CONCLUSIONS: MIC values of JNJ-17156581 and JNJ-17156815 were equivalent to 8-fold lower than those of telithromycin against H. influenzae, and macrolide-susceptible and -resistant Gram-positive cocci; ED[50] values were 2- to 3-fold lower than those of telithromycin when dosed s.c., and 7- and 2-fold lower than telithromycin, respectively, when dosed orally.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Bacterial Agents
• Haemophilus influenzae
• In Vitro
• Ketolides
• Microbial Sensitivity Tests
• Respiratory Tract Infections
• Streptococcus pneumoniae
• telithromycin

Other ID:

• GWAIDS0025841

UI: 102265465

From Meeting Abstracts