青霉素与阿奇霉素联合应用对肺炎链球菌疗效的研究

Combination of Penicillin and Azithromycin Against Streptococcus pneumoniae in Vitro and in Vivo

目的观察青霉素与阿奇霉素联合用药在体外及动物体内对肺炎链球菌的疗效,以指导临床用药。方法体外试验选用3株肺炎链球菌6305、2000099-1及标准株ATCC49619,通过棋盘法测定FIC指数(fractional inhibitory concentration,分级抑菌浓度)以判断青霉素与阿奇霉素联合用药对3株肺炎链球菌的抗菌活性;体内试验选用对青霉素及阿奇霉素均敏感的肺炎链球菌2000099-1作为试验用细菌。通过向小鼠气管内注入30μL菌悬液制备肺炎模型,绘制几种不同给药方法的时间-杀菌曲线判断联合用药疗效。结果体外试验中,3株链球菌的FIC值均在1～2之间,表现为无关作用;体内试验中,青霉素与阿奇霉素联合用药组6h肺组织细菌浓度较单用最有效组即阿奇霉素组减低<2lgCFU·mL-1,可判定为无关。结论青霉素与阿奇霉素联合用药在体外及鼠链球菌肺炎模型中均表现为无关作用,可作为社区获得性肺炎经验性治疗的参考。

OBJECTIVE To investigate the combination of penicillin and azithromycin against Streptococcus pneumoniae in vitro and in vivo and then to guide clinical medication. METHODS Three isolates orS. pneumoniae 6305, 2000099-1 and ATCC 49619 were used in vitro. FIC indices were calculated by the chequerboard method to evaluate the interactions between penicillin and azithromycin against three isolates of S. pneumoniae. S. pneumoniae 2000099-1 which was susceptible to both penicillin and azithromycin was used in vivo. Swiss mice were infected by the intratracheal route with 30 μL of bacterial suspension. The time-kiU curves of groups with different medication were obtained for the evaluation of antibiotic interactions. RESULTS The FIC index of three isolates were 1-2, and the combination was independent in vitro. The decrease of 〈2 1gCFU·mL^-1 of bacterial densities in the lungs was found in the combination group, compared with the group treated with the most effective agent used alone in vivo. The combination was considered as independent. CONCLUSION The combination of penicillin and azithromycin showed independent both in vitro and in vivo, this medication could be used for initial empirical treatment in community-acquired pneumonia.