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Antimicrobial Agents and Chemotherapy, January 2005, p. 309-315, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.309-315.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Novel 2-Fluoro-Naphthyridine-Containing Ketolides

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, New Jersey,¹ Kosan Biosciences, Hayward, California²

Received 5 May 2004/ Returned for modification 1 June 2004/ Accepted 20 September 2004

In vitro activities of erythromycin A, telithromycin, and two investigational ketolides, JNJ-17155437 and JNJ-17155528, were evaluated against clinical bacterial strains, including selected common respiratory tract pathogens. Against 46 macrolide-susceptible and -resistant Streptococcus pneumoniae strains, the MIC₉₀ (MIC at which 90% of the isolates tested were inhibited) of the investigational ketolides was 0.25 µg/ml, twofold lower than that of telithromycin and at least 64-fold lower than that of erythromycin A. Against erm(B)-containing pneumococci, the MIC₉₀ of all the ketolides was 0.06 µg/ml. The MIC₉₀ of the investigational ketolides against mef(A)-containing pneumococci or pneumococci with both mef(A) and erm(B) was 0.25 µg/ml, two-and fourfold lower, respectively, than that of telithromycin. In contrast, the MICs of the investigational ketolides against macrolide-resistant S. pneumoniae strains with ribosomal mutations were similar to or, in some cases, as much as eightfold higher than those of telithromycin. Against Haemophilus influenzae, MICs of all the ketolides were 2 µg/ml. Against three Moraxella catarrhalis isolates, the MIC of the ketolides was 0.25 µg/ml. The ketolides inhibited in vitro protein synthesis, with 50% inhibitory concentrations ranging from 0.23 to 0.27 µM. In time-kill studies against macrolide-susceptible and erm- or mef-containing pneumococci, the ketolides were bacteriostatic to slowly bactericidal, with 24-h log₁₀ decreases ranging from 2.0 to 4.1 CFU. Intervals of postantibiotic effects for the ketolides against macrolide-susceptible and -resistant S. pneumoniae were 3.0 to 8.1 h.

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