title: Comparative antimicrobial activity and kill-curve investigations of novel ketolide antimicrobial agents (HMR 3004 and HMR 3647) tested against Haemophilus influenzae and Moraxella catarrhalis strains.
abstract: The activity of two ketolide compounds, HMR 3004 and 3647, were compared to those of five macrolides, quinupristin/dalfopristin, ciprofloxacin, and ampicillin. The rate of killing for the ketolides was also assessed against Haemophilus influenzae and Moraxella catarrhalis. One hundred H. influenzae and 148 M. catarrhalis isolates were tested using broth microdilution and appropriate growth media. The killing rates of HMR 3004 and 3647 were analyzed using the time-kill method against five strains from each of the two species. Against H. influenzae, the activity of the ketolides (MIC90, 2 or 4 microg/mL) resembled that of azithromycin and quinupristin/dalfopristin and was more active than any tested macrolide. Against M. catarrhalis, HMR 3004 and 3647 were equally potent as azithromycin and clarithromycin (MIC50, 0.06 microg/mL and MIC90, 0.12 microg/mL) and more potent than all other macrolides or quinupristin/dalfopristin. Time-kill kinetic studies revealed that like the macrolide compounds, the ketolides are bacteristatic at or near the MIC for both H. influenzae and M. catarrhalis. This activity can be increased to a bactericidal level if the concentration is increased four- or eightfold the MIC for H. influenzae. In conclusion, HMR 3004 and 3647 have bacteristatic activity against tested respiratory pathogens and may prove to have an important role against macrolide-resistant isolates.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Biedenbach
authors.forename: M S
authors.initials: MS
authors.lastname: Barrett
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects*; D048628:Ketolides; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; C105420:RU 64004; C106791:telithromycin