Dudley M N, Blaser J, Gilbert D, Mayer K H, Zinner S H
Antiinfective Pharmacology Research Unit, University of Rhode Island College of Pharmacy, Providence 02908.
J Infect Dis. 1991 Sep;164(3):499-506. doi: 10.1093/infdis/164.3.499.
The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal beta-lactam with ciprofloxacin against P. aeruginosa.
在一个双室体外感染动力学模型中，研究了剂量给药方案对模拟人体剂量的环丙沙星（每12小时静脉注射200毫克）和阿洛西林（每12小时静脉注射4克）单独或联合使用对铜绿假单胞菌药效学的影响。使用同时给药或错开给药方案（每种药物的首剂间隔6小时给药）对两种药物联合使用的研究进行了比较。所有联合给药方案均能防止细菌再生长和耐药性；然而，同时给药方案始终对所有菌株提供最大程度的杀灭作用，特别是对那些最初对环丙沙星耐药的菌株。模型类似“血清”隔室中杀菌活性的峰值和持续时间增加，证实了联合用药的这些增强作用。这些数据表明，抗假单胞菌β-内酰胺类药物与环丙沙星同时给药对铜绿假单胞菌具有潜在的有用性。
