大鼠肺部与外周血清阿奇霉素浓度对肺炎链球菌抑菌作用的比较

 目的观察阿奇霉素在血清、支气管肺泡上皮表面液(ELF)、肺组织匀浆的浓度及随时间分布的特点,并进一步比较三者浓度对肺炎链球菌的抑制作用。方法为SD大鼠灌胃阿奇霉素后微生物法测血、支气管肺泡灌洗液及肺组织匀浆阿奇霉素浓度。ELF的阿奇霉素浓度按尿素稀释法算出。用肉汤微量稀释法测定阿奇霉素、青霉素对27株肺炎链球菌的最低抑菌浓度(MIC),比较血清、ELF和肺组织匀浆阿奇霉素浓度对肺炎链球菌的抑制作用。结果血清、ELF和肺组织匀浆中阿奇霉素浓度在首次给药后51 h最高,分别为(0.652 7±0.213 3),(1.325 5±0.280 3)和(29.094 2±2.940 2)mg·L^-1。青霉素对27株肺炎链球菌的敏感率为66.7%,高于阿奇霉素敏感率(14.8%);其中对阿奇霉素耐药的23株肺炎链球菌(85.2%)中,MIC>512 mg·L^-1的有16株(69.6%);除去美国疾病控制中心(CDC)的4株肺炎链球菌,仅有30.4%的菌株可被肺组织的峰浓度抑制,8.7%(2/23)可被ELF和血清的阿奇霉素浓度抑制。结论虽然阿奇霉素具有很高的肺组织浓度,并且超过了阿奇霉素中介或低度耐药的肺炎链球菌的MIC水平,但不能单以血清浓度预测阿奇霉素对病原体的抗菌效果。

Comparative Effects of Azithromycin in Lung and Peripheral Blood Serum of Rats Against Streptococcus Pneumoniae

OBJECTIVE To investigate azithromycin concentrations and time courses in serum,epithelial lining fluid(ELF)and lung homogenate after the administration of azithromycin for rats and then compare their inhibitory effects on Streptococcus pneumoniae.METHODS Azithromycin was given to SD rats through an esophageal catheter.Azithromycin levels in serum,bronchoalveolar lavage fluid and lung homogenate were determined by an agar well diffusion bioassay technique.The concentration of azithromycin in ELF determined by means of the urea dilution method.The minimal inhibitory concentrations(MIC)of azithromycin and penicillin for the 27 strains of Streptococcus pneumoniae were determined by the broth microdilution method.Then the inhibitory effects of azithromycin in serum,ELF,and lung homogenate on Streptococcus pneumoniae were compared.RESULTS With the employed sampling schedule,the azithromycin concentrations in serum,ELF and lung homogenate were all highest 51 h after the initial dose and declined thereafter,which were(0.652 7±0.213 3),(1.325 5±0.280 3) and(29.094 2±2.940 2) mg·L^-1,respectively.The susceptibal rate of penicillin to 27 isolates of Streptococcus pneumoniae was 66.7%,which was higher than that of azithromycin(14.8%).Among 23 strains(85.2%) which were resistant to azithromycin,16 isolates were(MIC>512) mg·L^-1(69.6%). Except for 4 strains provided by American Center of Diseases Control(CDC),only 30.4% isolates were inhibited by the azithromycin peak concentration in lung homogenate.While the inhibitation rate of Streptococcus pneumoniae strains in ELF and peripheral blood serum concentrations was 8.7%.CONCLUSION Even though azithromycin concentration in lung is higher than intermidiea or low grade resistant Streptococcus pneumoniae strains,we shouldn't predict the potential efficacy of azithromycin in serum on pathogens.