摘要
目的静脉注射不同剂量的去甲万古霉素,了解其在耐青霉素肺炎链球菌引起的兔脑膜炎模型中的脑脊液透过率;比较不同剂量药物的杀菌效果;同时研究去甲万古霉素与磷霉素联合用药在体内、体外是否具有协同作用。方法脑膜炎模型的建立参照Dacey和Sande的方法并做了改进;抗生素浓度的测定采用微生物效价测定法;体外联合药敏实验采用棋盘设定微量肉汤稀释法。以8h内的平均杀菌率评估体内联合用药。结果在兔脑膜炎模型中,去甲万古霉素的脑脊液透过率为19.6%;40mg/kg去甲万古霉素单次静脉注射(0h)平均杀菌率为(-0.93±0.26)△lgCFU/(ml·h);20mg/kg去甲万古霉素两次静脉注射(0,4h)平均杀菌率为(-0.57±0.45)△lgCFU/(ml·h)。体外联合药敏实验表明磷霉素与去甲万古霉素联合应用表现为相加作用占25%,无关作用占75%,无协同或拮抗作用。体内三种不同剂量的磷霉素与去甲万古霉素联合应用,三组的平均杀菌率分别为(-0.45±0.21)△lgCFU/(ml·h)、(-0.46±0.25)△lgCFU/(ml·h)、(-0.42±0.28)△lgCFU/(ml·h),三者之间无明显差别。结论在耐青霉素肺炎链球菌致脑膜炎的兔模型中,去甲万古霉素的脑脊液透过率与万古霉素相似,但同等剂量条件下,去甲万古霉素的杀菌效果明显好于万古霉素。磷霉素不适于单独治疗耐青霉素肺炎链球菌所致脑膜炎,体外及体内实验证实磷霉素与去甲万古霉素联合应用分别表现为无关作用和拮抗作用。
Objective To investigate the cerbrospinal fluid （CSF） penetration of norvancomycin in meningitis models caused by a penicillin-resistant Streptococcus pneumoniae, and compare the killing rate after the different dosages of the regimens were administratered, and to investigate if there was a synergistic action when fosfomycin was in combination with norvancomycin in vivo and in vitro. Methods The rabbit meningitis model, originally described by Dacey and Sande, was slightly modified. Antibiotic concentrations were determined by agar diffusion method. Synergy was demonstrated between norvancomycin and fosfomycin by the checkerboard method in vitro and by time-killing assays over 8h in vivo. Result When norvancomycin （40mg/kg） was administrated at Oh, the average killing rate was （ -0. 93 ±0. 26） △IgCFU/（ml · h）; while norvancomycin （20mg/kg） was administratered at Oh and 4h, the average killing rate was （ -0.57 ±0. 45）△IgCFU/（ml·h）. In vitro, the distribution of FIC index demonstrated that 25% of them showed additive effect and 75% of them were indifferent, there was no action of synergy and antagonism. In vivo, three-different dose combination of norvancomycin with fosfomycin showed no difference in killing rate. Conclusion The CSF penetration of norvancomycin in meningitis model was similar to that of vancomycin. But at the same dosage, the antimicrobial activity of norvancomycin was much better than vancomycin. Fosfomycin was not suitable, as a single agent, to treat bacterial meningitis caused by penicillin-resistant Streptococcus pneumoniae. The combination of norvancomycin with fosfomycin demonstrated indifferent chiefly in vitro, but in vivo antagonism was demonstrated.
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2006年第7期432-436,共5页
Chinese Journal of Antibiotics
关键词
去甲万古霉素
肺炎链球菌
脑膜炎模型
药动学
药效学
Norvancomycin
Streptococcus pneumoniae
Meningitis model
Pharmacokinetic
Pharmacodynamic
