头孢噻利不同剂量单次静滴在中国健康人群的血清杀菌活性

Serum bactericidal activity of different single intravenous doses of cefoselis in Chinese healthy volunteers

目的研究单次静滴不同剂量头孢噻利在中国健康受试者的血清杀菌活性(SBA)。方法 12名健康受试者单次静滴不同剂量头孢噻利后,于0.5 h(峰时)和5,8,12 h(谷时)采血,微量肉汤稀释法测定不产酶阴沟肠杆菌、产AmpC酶的阴沟肠杆菌和甲氧西林敏感金黄色葡萄球菌(MSSA)的最低抑菌浓度(MIC)及SBA,计算其达标率。结果头孢噻利对3种致病菌均敏感;单次静滴不同剂量头孢噻利在给药后0.5 h,对3种致病菌的SBA均为>1∶1～1∶64;峰时,对产AmpC酶阴沟肠杆菌的同一时间、不同剂量组间的SBA中位数秩和检验差异有统计学意义(P<0.05),不产酶阴沟肠杆菌和MSSA差异无统计学意义(P>0.05);同一菌种不同剂量的SBA中位数差异均无统计学意义(P>0.05)。峰时SBA≥1∶8百分率,不同剂量组间差异均无统计学意义(P>0.05),且峰时SBA≥1∶8百分率对3种致病菌均达88%以上;谷时及其他时间点SBA≥1∶1的百分率,在不产酶阴沟肠杆菌和MSSA部分差异有统计学意义(P<0.05)。结论头孢噻利不同剂量对临床分离的产AmpC酶和不产酶的阴沟肠杆菌与MSSA均有较强的体内杀菌活性。

Objective To compare the serum bactericidal activity（SBA） of different single intravenous doses of cefoselis（CFSL） in Chinese healthy volunteers.Methods The minimal inhibitory concentration（MIC） of cefoselis against Enterobacter cloacae not producing enzyme / producing AmpC enzyme,and methicillin susceptible Staphylococcus aureus（MSSA） were determined by microdilution method.Twelve healthy volunteers were given three single intravenous doses of cefoselis respectively and blood sample were collected at 0.5 h（peak） and 5,8,12 h（valley） after infusion.The SBA was determined by broth microdilution method,and the rate of SBA were analysed.Results The three clinical pathogens were sensitive to cefoselis.The SBA of three clinical pathogens were all 1∶1~1∶64 for o.5 h（peak） after cefoselis infusion.The range of SBA for Enterobacter cloacae producing AmpC enzyme and MSSA increased slightly with the increase of doses.At the peak of curve,the SBA median of different dose groups for Enterobacter cloacae producing AmpC enzyme were statistically significant（P0.05）.The SBA median of different dose groups for Enterobacter cloacae not producing AmpC enzyme and MSSA were not statistically significant（P0.05）.The SBA median of different dose groups for same kind of pathogens were not statistically significant（P0.05）.The percentages of SBA were assessed with chi-square statistics.The percentages of SBA≥1∶8（peak） for three clinical pathogens were not statistically significant（P0.05）.Some of the percentages of SBA≥1∶1（valley and other time） for Enterobacter cloacae not producing AmpC enzyme and MSSA were statistically significant（P0.05）.Conclusion The strong in vivo antibacterial activity of cefoselis to Enterobacter cloacae not producing enzyme / producing AmpC enzyme,Enterobacter cloacae producing AmpC enzyme and MSSA,and there will be a better clinical efficacy as predicted.