Stein Gary E, Schooley Sharon, Tyrrell Kerin L, Citron Diane M, Goldstein Ellie J C
Department of Medicine, B320 Life Sciences Building, Michigan State University, East Lansing, MI 48824, USA.
Int J Antimicrob Agents. 2007 Jan;29(1):39-43. doi: 10.1016/j.ijantimicag.2006.08.041.
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.
泰利霉素是一种新型酮内酯类抗菌药物，对需氧和厌氧呼吸道病原体均具有良好的体外活性。在本研究中，我们评估了单次口服泰利霉素（800mg）、阿奇霉素（500mg）和阿莫西林/克拉维酸（875/125mg）后，10名健康受试者血清中这些药物随时间的抗菌活性。在每次给药后的2、6、12和24小时测定抑菌和杀菌效价，并使用中位效价来确定抗菌活性。对于两株阿奇霉素耐药的肺炎链球菌，泰利霉素（MIC = 0.25和0.5μg/mL）和阿莫西林/克拉维酸均表现出至少6小时的抑菌和杀菌活性。所有三种抗生素对流感嗜血杆菌菌株均提供了延长（≥12小时）的抑菌活性（泰利霉素MIC = 4.0μg/ml）。泰利霉素和阿莫西林/克拉维酸对所研究的每种厌氧菌（大芬戈尔德菌[消化链球菌]、微小消化链球菌、二路普雷沃菌和产黑素普雷沃菌）均表现出快速且延长（≥12小时）的抑菌活性。此外，两种药物对两种普雷沃菌属均具有杀菌活性。在这项体外药效学研究中，我们发现泰利霉素在血清中对耐大环内酯类肺炎链球菌菌株、β-内酰胺酶阳性和阴性流感嗜血杆菌菌株以及常见呼吸道厌氧病原体具有快速且延长的抗菌活性。这些发现表明，泰利霉素在治疗社区获得性需氧-厌氧混合性呼吸道感染，包括慢性鼻窦炎和吸入性肺炎方面可能具有临床应用价值。
