Roosendaal R, Bakker-Woudenberg I A, van den Berghe-van Raffe M, Michel M F
Antimicrob Agents Chemother. 1986 Sep;30(3):403-8. doi: 10.1128/AAC.30.3.403.
Experimental Klebsiella pneumoniae pneumonia was used to study the influence of cyclophosphamide-induced leukopenia on the relative therapeutic efficacy of continuous and intermittent (6-h intervals) administration of ceftazidime. The antimicrobial response was evaluated with respect to the calculated daily dose that protected 50% of the animals from death (PD50) until 16 days after the termination of a 4-day treatment. When ceftazidime was administered intermittently to leukopenic rats, the PD50 was 24.37 mg/kg per day, 70 times (P less than 0.001) the PD50 of 0.35 mg/kg per day for normal rats. Continuous administration of ceftazidime to leukopenic rats resulted in a PD50 of 1.52 mg/kg per day, four times (P less than 0.001) the PD50 of 0.36 mg/kg per day for normal rats. Continuous administration of ceftazidime in daily doses that protected 100% of normal and leukopenic rats from death resulted in serum levels of 0.06 and 0.38 micrograms/ml, respectively, whereas the MIC for the infecting K. pneumoniae strain was 0.2 micrograms of ceftazidime per ml. The effect of the duration of ceftazidime treatment by continuous infusion on the therapeutic efficacy in relation to the persistence of leukopenia was then investigated in leukopenic rats. The administration of 3.75 mg of ceftazidime/kg per day for 4 days protected all leukopenic rats from death, provided the circulating leukocytes returned at the end of antibiotic treatment. When leukopenia persisted for 8 days this ceftazidime treatment schedule resulted in the mortality of rats (P less than 0.05). However, when ceftazidime treatment was continued for 8 days, until the return of the leukocytes, there was no significant mortality (P greater than 0.05).
采用实验性肺炎克雷伯菌肺炎模型，研究环磷酰胺诱导的白细胞减少对头孢他啶持续给药和间歇给药（间隔6小时）相对治疗效果的影响。根据保护50%的动物免于死亡的计算日剂量（PD50）评估抗菌反应，直至4天治疗结束后16天。当对白细胞减少的大鼠间歇给予头孢他啶时，PD50为每天24.37mg/kg，是正常大鼠每天0.35mg/kg的PD50的70倍（P<0.001）。对白细胞减少的大鼠持续给予头孢他啶，导致PD50为每天1.52mg/kg，是正常大鼠每天0.36mg/kg的PD50的4倍（P<0.001）。以能保护100%正常和白细胞减少大鼠免于死亡的日剂量持续给予头孢他啶，血清水平分别为0.06和0.38μg/ml，而感染的肺炎克雷伯菌菌株的最低抑菌浓度为每毫升0.2μg头孢他啶。然后在白细胞减少的大鼠中研究持续输注头孢他啶的治疗持续时间对治疗效果与白细胞减少持续时间关系的影响。每天给予3.75mg/kg头孢他啶，持续4天，可保护所有白细胞减少的大鼠免于死亡，前提是抗生素治疗结束时循环白细胞恢复。当白细胞减少持续8天时，这种头孢他啶治疗方案导致大鼠死亡（P<0.05）。然而，当头孢他啶治疗持续8天，直至白细胞恢复时，则无显著死亡率（P>0.05）。
