Peterson L R, Moody J A, Fasching C E, Gerding D N
Department of Medicine, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Antimicrob Agents Chemother. 1989 Apr;33(4):566-8. doi: 10.1128/AAC.33.4.566.
The effect of protein binding of cefoperazone (89.3% bound to rabbit serum) on antibacterial activity in serum was tested in a model that simulated a closed-space infection in a neutropenic host. Four gram-negative bacilli were tested in the model with cefoperazone doses of 20 and 200 mg/kg administered intramuscularly every 6 h for 16 doses. Cefoperazone efficacy was measured at 92 h by determining the log10 decrease in bacterial count from that of the control for five paired studies with three isolates. A significantly better response was demonstrated when the free (non-protein-bound) drug concentration exceeded the MICs and MBCs for the infecting microorganisms at the infection site at all times (P less than 0.005). This supports the concept that free (unbound) drug is the active component in treating bacterial infections.
在一个模拟中性粒细胞减少宿主封闭空间感染的模型中，测试了头孢哌酮蛋白结合率（与兔血清的结合率为89.3%）对血清中抗菌活性的影响。在该模型中，对4种革兰氏阴性杆菌进行了测试，头孢哌酮剂量为20和200mg/kg，每6小时肌肉注射1次，共注射16次。在92小时时，通过测定5项配对研究中3种分离株相对于对照的细菌计数的log10下降来衡量头孢哌酮的疗效。当游离（非蛋白结合）药物浓度在所有时间都超过感染部位感染微生物的MIC和MBC时，显示出显著更好的反应（P小于0.005）。这支持了游离（未结合）药物是治疗细菌感染的活性成分这一概念。
