title: Human serum activity of telithromycin, azithromycin and amoxicillin/clavulanate against common aerobic and anaerobic respiratory pathogens.
abstract: Telithromycin is a new ketolide antimicrobial with a good in vitro activity against both aerobic and anaerobic respiratory pathogens. In this study, we evaluated the antibacterial activity over time of telithromycin (800mg), azithromycin (500mg), and amoxicillin/clavulanate (875/125mg) in serum following single oral doses of these agents to 10 healthy subjects. Inhibitory and bactericidal titers were determined at 2, 6, 12, and 24h after each dose and the median titer was used to determine antibacterial activity. Against two azithromycin-resistant strains of Streptococcus pneumoniae, both telithromycin (MIC=0.25 and 0.5 microg/mL) and amoxicillin/clavulanate exhibited inhibitory and cidal activity for at least 6h. All three antibiotics provided prolonged (>or=12h) inhibitory activity against strains of Hemophilus influenzae (telithromycin MIC=4.0 microg/ml). Both telithromycin and amoxicillin/clavulanate exhibited rapid and prolonged inhibitory activity (>or=12h) against each of the anaerobes studied (Finegoldia [Peptostreptococcus] magna Peptostreptococcus micros, Prevotella bivia, and Prevotella melaninogenica). Moreover, both agents provided bactericidal activity against both Prevotella species. In this ex vivo pharmacodynamic study, we found that telithromycin provided rapid and prolonged antibacterial activity in serum against macrolide-resistant strains of S. pneumoniae, beta-lactamase-positive and -negative strains of H. influenzae, and common respiratory anaerobic pathogens. These findings suggest that telithromycin could have clinical utility in the treatment of community-acquired mixed aerobic-anaerobic respiratory tract infections, including chronic sinusitis and aspiration pneumonia.
authors.affiliation: Department of Medicine, B320 Life Sciences Building, Michigan State University, East Lansing, MI 48824, USA. steing@msu.edu
authors.forename: Gary E
authors.initials: GE
authors.lastname: Stein
authors.forename: Sharon
authors.initials: S
authors.lastname: Schooley
authors.forename: Kerin L
authors.initials: KL
authors.lastname: Tyrrell
authors.forename: Diane M
authors.initials: DM
authors.lastname: Citron
authors.forename: Ellie J C
authors.initials: EJ
authors.lastname: Goldstein
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D017963:Azithromycin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001420:Bacteria, Aerobic / Q000187:drug effects; D001421:Bacteria, Anaerobic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D048628:Ketolides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010462:Peptostreptococcus / Q000187:drug effects; D018720:Prevotella / Q000187:drug effects; D001443:Prevotella melaninogenica / Q000187:drug effects; D015610:Serum Bactericidal Test; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D019980:Amoxicillin-Potassium Clavulanate Combination; D017963:Azithromycin; C106791:telithromycin