Stein G E, Schooley S
Michigan State University, Department of Medicine, Division of Infectious Diseases, B-320 Life Sciences Bldg., East Lansing, MI 48824, USA.
Diagn Microbiol Infect Dis. 2001 Mar;39(3):181-5. doi: 10.1016/s0732-8893(00)00239-x.
The serum pharmacodynamics of clarithromycin and azithromycin were studied against isolates of S. pneumoniae, including efflux resistant (M. phenotype) strains, by analyzing their serum bactericidal activity (SBA) over time. Normal healthy subjects were given a single 500 mg oral dose of these macrolides and serum samples were collected over 12 hrs. Paired isolates with MICs ranging from 0.25 ug/ml to 8.0 ug/ml were analyzed. Prolonged (at least 6 hrs) SBA was observed with clarithromycin for strains with MICs < or = 2.0 ug/ml. No SBA was observed in strains with MICs >or = 4.0 ug/ml. Azithromycin exhibited SBA for at least 6 hrs for strains up to a MIC = 0.5 ug/ml. No SBA was observed for isolates with MICs > or = 1.0 ug/ml. In contrast to azithromycin, clarithromycin exhibited SBA for at least one-half of its normal dosing interval against S. pneumoniae strains well above its current susceptibility breakpoint concentration of 0.25 microg/ml. These findings may have relevance to the ongoing debate as to the appropriate susceptibility breakpoints for the newer macrolides.
通过分析克拉霉素和阿奇霉素随时间的血清杀菌活性（SBA），研究了它们对肺炎链球菌分离株（包括外排耐药M表型菌株）的血清药效学。给正常健康受试者单次口服500mg这些大环内酯类药物，并在12小时内收集血清样本。分析了MIC范围为0.25μg/ml至8.0μg/ml的配对分离株。对于MIC≤2.0μg/ml的菌株，克拉霉素观察到SBA延长（至少6小时）。对于MIC≥4.0μg/ml的菌株，未观察到SBA。对于MIC = 0.5μg/ml的菌株，阿奇霉素表现出至少6小时的SBA。对于MIC≥1.0μg/ml的分离株，未观察到SBA。与阿奇霉素不同，克拉霉素在其正常给药间隔的至少一半时间内对肺炎链球菌菌株表现出SBA，这些菌株远高于其当前0.25μg/ml的敏感断点浓度。这些发现可能与关于新型大环内酯类药物适当敏感断点的持续争论有关。
