Shyu W C, Nightingale C H, Quintiliani R
J Antimicrob Chemother. 1987 Jun;19(6):807-14. doi: 10.1093/jac/19.6.807.
Peritonitis in neutropenic rats, caused by a strain of Pseudomonas aeruginosa resistant to amikacin and ticarcillin alone but susceptible to ceftazidime and combinations of amikacin with ticarcillin, amikacin with ceftazidime and ticarcillin with ceftazidime, was investigated. Four hours after a bacterial challenge with a LD70 intraperitoneal dose of P. aeruginosa (1.5 X 10(8) cfu/ml), either amikacin, ticarcillin, ceftazidime, amikacin-ticarcillin, amikacin-ceftazidime, or ticarcillin-ceftazidime was administered at dosing intervals that mimicked the serum concentrations of the drugs found in humans after therapeutic doses. When the serum concentrations did not exceed the MIC, as occurred with amikacin, no difference in survival was observed compared with controls. All other regimens resulted in animal survival during the treatment. When therapy was stopped only those regimens resulting in serum concentrations above the MBC were effective (amikacin-ticarcillin, amikacin-ceftazidime, ticarcillin-ceftazidime). The recovery of viable bacteria from the peritoneum agreed well with mortality.
研究了中性粒细胞减少大鼠的腹膜炎,该腹膜炎由一株仅对阿米卡星和替卡西林耐药但对头孢他啶以及阿米卡星与替卡西林联用、阿米卡星与头孢他啶联用、替卡西林与头孢他啶联用敏感的铜绿假单胞菌引起。在用腹腔注射剂量为LD70的铜绿假单胞菌(1.5×10⁸ cfu/ml)进行细菌攻击4小时后,按照模拟治疗剂量后人体血清中发现的药物浓度的给药间隔,给予阿米卡星、替卡西林、头孢他啶、阿米卡星 - 替卡西林、阿米卡星 - 头孢他啶或替卡西林 - 头孢他啶。当血清浓度未超过最低抑菌浓度(MIC)时,如阿米卡星的情况,与对照组相比,未观察到存活率有差异。所有其他治疗方案在治疗期间都使动物存活。当停止治疗时,只有那些导致血清浓度高于最低杀菌浓度(MBC)的治疗方案是有效的(阿米卡星 - 替卡西林、阿米卡星 - 头孢他啶、替卡西林 - 头孢他啶)。从腹膜中回收的活菌数量与死亡率非常吻合。