Juvin M E, Drugeon H B, Bigot E, Caillon J
Pathol Biol (Paris). 1986 Jun;34(5 Pt 2):554-8.
Third-generation cephalosporins such as ceftriaxone are often used alone; however, with Enterobacter (ENT), Citrobacter (CIT), Serratia (SER) and Morganella (MOR), a combination of two drugs is advisable. Aminoglycoside-beta-lactam combinations are often synergistic. However, results are not consistent with the new cephalosporins. We determined the killing kinetics of ceftriaxone (C) alone, amikacin (A) alone and both drugs in combination (AC). The antibiotics were tested in the following concentrations: 0.25, 1, 4 and 16 X MIC for C, 0.5, 2 and 8 X MIC for A, and, for AC, 0.5-0.25 X MIC (1), 0.5-1 X MIC (2) and 2-0.25 X MIC (3). Surviving bacteria were enumerated at 0 h, 1 h, 3 h, 5 h and 24 hours. Amikacin showed a strong, dose-dependent bactericidal activity. Maximal activity of ceftriaxone was observed at 1 or 4 X MIC. Time of contact had a significant influence, indicating a time-dependent activity. In 5 hours, the killing effect of the AC combination rarely exceeded that of each antibiotic alone. Higher killing rates were observed with AC and; the killing effect of AC (3) was similar to amikacin's maximal killing effect. In 24 hours, the AC (3) combination was clearly synergistic with inhibition of late regrowths.
第三代头孢菌素如头孢曲松通常单独使用；然而，对于肠杆菌属（ENT）、柠檬酸杆菌属（CIT）、沙雷氏菌属（SER）和摩根氏菌属（MOR），建议联合使用两种药物。氨基糖苷类-β-内酰胺类联合用药通常具有协同作用。然而，与新型头孢菌素联合使用的结果并不一致。我们测定了头孢曲松（C）单独使用、阿米卡星（A）单独使用以及两种药物联合使用（AC）时的杀菌动力学。测试的抗生素浓度如下：C为0.25、1、4和16倍最低抑菌浓度（MIC），A为0.5、2和8倍MIC，对于AC联合用药，分别为0.5 - 0.25倍MIC（1）、0.5 - 1倍MIC（2）和2 - 0.25倍MIC（3）。在0小时、1小时、3小时、5小时和24小时对存活细菌进行计数。阿米卡星表现出强烈的剂量依赖性杀菌活性。头孢曲松在1或4倍MIC时观察到最大活性。接触时间有显著影响，表明其活性具有时间依赖性。在5小时内，AC联合用药的杀菌效果很少超过每种抗生素单独使用的效果。AC联合用药的杀菌率更高；AC（3）的杀菌效果与阿米卡星的最大杀菌效果相似。在24小时时，AC（3）联合用药明显具有协同作用，可抑制后期细菌再生长。
