title: In vitro activities of novel 2-fluoro-naphthyridine-containing ketolides.
abstract: 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 MIC(90) (MIC at which 90% of the isolates tested were inhibited) of the investigational ketolides was 0.25 microg/ml, twofold lower than that of telithromycin and at least 64-fold lower than that of erythromycin A. Against erm(B)-containing pneumococci, the MIC(90) of all the ketolides was 0.06 microg/ml. The MIC(90) of the investigational ketolides against mef(A)-containing pneumococci or pneumococci with both mef(A) and erm(B) was 0.25 microg/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 < or =2 microg/ml. Against three Moraxella catarrhalis isolates, the MIC of the ketolides was 0.25 microg/ml. The ketolides inhibited in vitro protein synthesis, with 50% inhibitory concentrations ranging from 0.23 to 0.27 microM. In time-kill studies against macrolide-susceptible and erm- or mef-containing pneumococci, the ketolides were bacteriostatic to slowly bactericidal, with 24-h log(10) 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.
authors.affiliation: Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Raritan, NJ 08869, USA. dabbanat@prdus.jnj.com
authors.forename: Darren
authors.initials: D
authors.lastname: Abbanat
authors.forename: Glenda
authors.initials: G
authors.lastname: Webb
authors.forename: Barbara
authors.initials: B
authors.lastname: Foleno
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Mark
authors.initials: M
authors.lastname: Macielag
authors.forename: Deborah
authors.initials: D
authors.lastname: Montenegro
authors.forename: Ellyn
authors.initials: E
authors.lastname: Wira
authors.forename: Karen
authors.initials: K
authors.lastname: Bush
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D048628:Ketolides / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*; D012141:Respiratory Tract Infections / Q000382:microbiology*; D013210:Staphylococcus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; C496528:JNJ 17155437; C496529:JNJ 17155528; D048628:Ketolides; D009287:Naphthyridines; D004917:Erythromycin; C106791:telithromycin