Haller I
Infection. 1982;10 Suppl 3:S229-33. doi: 10.1007/BF01640679.
The effect of decreasing concentrations of azlocillin and sisomicin on Pseudomonas aeruginosa was examined. Logarithmically growing bacterial cultures were incubated in an ultrafiltration cell, and after adding the antibiotics, the culture medium was diluted every 20 min without any decrease in cell density. The turn-over of medium resulted in the elimination of azlocillin with a half-life of 75 min. This simulated serum kinetics in vivo. When testing sisomicin, small amounts of this agent were added during every dilution step to achieve a half-life of 120 min. Growth conditions were comparable in all experiments. The simultaneous combination of azlocillin and sisomicin resulted in strong synergism as assessed by higher killing rates and more prolonged growth inhibition of surviving bacteria. Comparable results were observed when both drugs were added at intervals of 40 min. When applied at intervals of 120 min, the combined effect of azlocillin and sisomicin was reduced, but still superior to the effect of double the concentration of each compound alone. Thus, neither pre-treatment with azlocillin nor with sisomicin impaired the antibacterial activity of the combination partner. This seems to be of clinical importance since the agents may be administered at different times during combined therapy.
研究了阿洛西林和西索米星浓度降低对铜绿假单胞菌的影响。对数生长期的细菌培养物在超滤池中培养，加入抗生素后，培养基每20分钟稀释一次，细胞密度无任何下降。培养基的更替导致阿洛西林消除，半衰期为75分钟。这模拟了体内血清动力学。检测西索米星时，在每个稀释步骤中加入少量该药物以达到120分钟的半衰期。所有实验中的生长条件均可比。通过更高的杀菌率和对存活细菌更长时间的生长抑制评估，阿洛西林和西索米星的联合使用产生了强烈的协同作用。当两种药物每隔40分钟添加一次时，观察到了类似的结果。当每隔120分钟应用时，阿洛西林和西索米星的联合作用降低，但仍优于每种化合物双倍浓度单独使用的效果。因此，先用阿洛西林或西索米星预处理均不会损害联合用药伙伴的抗菌活性。这似乎具有临床重要性，因为在联合治疗期间，这些药物可能在不同时间给药。
