Schaad U B, Grimm L M, Beskid G, Cleeland R, Nelson J D, McCracken G H
Infection. 1982;10(2):90-6. doi: 10.1007/BF01816731.
The activity of mecillinam, ampicillin and moxalactam alone and in combination was determined in a lapin meningitis model and a mouse meningitis model against two Escherichia coli strains isolated from infants with meningitis. Both strains were highly susceptible in vitro to the antibiotics, and responded well in systemic mouse protection tests (PD50 less than 4 mg/kg). Continuous infusion of mecillinam in the lapin model over nine hours was effective in sterilizing the CSF of three of four animals infected with one strain. This prompt bacteriologic response to mecillinam alone precluded the possibility of constant infusion administration for synergy studies. Therefore, single dose administration was used to demonstrate the synergistic potential of mecillinam with ampicillin in the lapin meningitis model against the E. coli Kl # 2 strain. The combination of moxalactam and mecillinam was synergistic against the E. coli Kl # 2 strain in the mouse meningitis model. The synergistic potential of these combinations could not be reliably predicted by in vitro tests, time kill curves or systemic mouse protection tests.
在兔脑膜炎模型和小鼠脑膜炎模型中，测定了美西林、氨苄西林和莫拉卡坦单独及联合使用时对从患脑膜炎婴儿分离出的两株大肠杆菌的活性。这两株菌在体外对这些抗生素均高度敏感，且在全身性小鼠保护试验中反应良好（半数保护剂量小于4mg/kg）。在兔模型中，对感染其中一株菌的四只动物中的三只，连续九小时输注美西林可有效清除脑脊液中的细菌。对美西林的这种迅速的细菌学反应排除了为协同研究进行持续输注给药的可能性。因此，在兔脑膜炎模型中采用单剂量给药来证明美西林与氨苄西林联合针对大肠杆菌K1#2菌株的协同潜力。在小鼠脑膜炎模型中，莫拉卡坦与美西林联合对大肠杆菌K1#2菌株具有协同作用。这些联合用药的协同潜力无法通过体外试验、时间杀菌曲线或全身性小鼠保护试验可靠预测。
