Freeman C D, Nightingale C H, Nicolau D P, Belliveau P P, Quintiliani R
College of Pharmacy, Butler University, Indianapolis, IN 46208.
Am J Hosp Pharm. 1994 Jul 15;51(14):1782-7.
The activity of ceftriaxone plus metronidazole against pathogens usually involved in intra-abdominal infections was studied. Metronidazole 1 g and ceftriaxone 1 g (as the sodium salt) were simultaneously administered i.v. over 30 minutes every 24 hours to 12 healthy volunteers for three doses. Serum samples were collected at baseline, just before the last dose, and 12, 16, 20, 22, and 24 hours after the start of infusion of the last dose. Serum bactericidal titers (SBTs) were performed in duplicate for each serum sample from 12 hours on. Serum ceftriaxone and metronidazole concentrations were determined by high-performance liquid chromatography, and the elimination rate and half-life were calculated for each antimicrobial in each volunteer. The minimum inhibitory concentrations (MICs) of each antibiotic for two strains each of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Bacteroides fragilis were determined by microdilution. Eleven volunteers completed the study. Ceftriaxone and metronidazole maintained SBTs of at least 1:4. Serum ceftriaxone concentrations remained above the MICs for E. coli, P. mirabilis, and K. pneumoniae, and serum metronidazole concentrations remained above the MIC for B. fragilis throughout the study. Ceftriaxone combined with metronidazole resulted in intense and prolonged activity against E. coli, P. mirabilis, K. pneumoniae, and B. fragilis.
研究了头孢曲松加甲硝唑对通常引起腹腔内感染的病原体的活性。每24小时一次，将1克甲硝唑和1克头孢曲松（钠盐）在30分钟内静脉注射给12名健康志愿者，共注射三剂。在基线、最后一剂前、最后一剂输注开始后12、16、20、22和24小时采集血清样本。从12小时起，对每个血清样本进行两次血清杀菌效价（SBT）检测。通过高效液相色谱法测定血清中头孢曲松和甲硝唑的浓度，并计算每名志愿者每种抗菌药物的消除率和半衰期。通过微量稀释法测定每种抗生素对大肠杆菌、奇异变形杆菌、肺炎克雷伯菌和脆弱拟杆菌各两株菌株的最低抑菌浓度（MIC）。11名志愿者完成了研究。头孢曲松和甲硝唑维持SBT至少为1:4。在整个研究过程中，血清头孢曲松浓度保持在高于大肠杆菌、奇异变形杆菌和肺炎克雷伯菌MIC的水平，血清甲硝唑浓度保持在高于脆弱拟杆菌MIC的水平。头孢曲松与甲硝唑联合使用对大肠杆菌、奇异变形杆菌、肺炎克雷伯菌和脆弱拟杆菌具有强烈且持久的活性。
