Odio C, Thomas M L, McCracken G H
Antimicrob Agents Chemother. 1984 Apr;25(4):427-32. doi: 10.1128/AAC.25.4.427.
The purpose of this study was to determine the pharmacokinetics and bacteriological effect of mezlocillin in experimental meningitis caused by Listeria monocytogenes and two Escherichia coli strains. The half-life of mezlocillin in cerebrospinal fluid (CSF) was approximately twice that in serum of experimentally infected animals, and the penetration of drug into CSF was 5 to 15% after a single dose and 5 to 20% after continuous-infusion experiments. The bactericidal titer in CSF for both susceptible E. coli and L. monocytogenes was 1:8, whereas for the resistant E. coli strain, titers were less than 1:2 after single doses of 50 or 100 mg of mezlocillin per kg and 1:4 with continuous infusion. After single-dose and continuous-infusion experiments, the bacteriological effect of mezlocillin in experimental L. monocytogenes infections was similar to that of ampicillin. Mezlocillin reduced the colony counts of of susceptible E. coli in CSF by 90% or more after a single dose or continuous infusion but had no appreciable effect on resistant E. coli after a single dose of 50 mg/kg. In contrast, a single dose of 100 mg of mezlocillin per kg eradicated the resistant strain from CSF, despite a bactericidal titer in CSF of less than 1:2. This unexpected finding prompted us to evaluate the effect of serum on the in vitro susceptibilities of selected coliforms to mezlocillin. The activity of mezlocillin against one susceptible and four resistant strains of gram-negative, enteric bacilli was enhanced manyfold by the addition of fresh rabbit serum; this effect was abolished by heating the serum at 56 degrees C for 30 min. This interaction of mezlocillin and serum against coliform bacteria should be examined in a larger number of experimentally infected animals and in specimens obtained from mezlocillin-treated infants.
本研究的目的是确定美洛西林在由单核细胞增生李斯特菌和两种大肠杆菌菌株引起的实验性脑膜炎中的药代动力学和细菌学效应。在实验感染动物中，美洛西林在脑脊液（CSF）中的半衰期约为血清中的两倍，单次给药后药物进入脑脊液的渗透率为5%至15%，连续输注实验后为5%至20%。对于敏感的大肠杆菌和单核细胞增生李斯特菌，脑脊液中的杀菌效价均为1:8，而对于耐药大肠杆菌菌株，每千克体重单次给予50或100毫克美洛西林后效价低于1:2，连续输注时为1:4。在单次给药和连续输注实验后，美洛西林在实验性单核细胞增生李斯特菌感染中的细菌学效应与氨苄西林相似。单次给药或连续输注后，美洛西林可使脑脊液中敏感大肠杆菌的菌落计数减少90%或更多，但每千克体重单次给予50毫克美洛西林后对耐药大肠杆菌无明显影响。相比之下，每千克体重单次给予100毫克美洛西林可从脑脊液中根除耐药菌株，尽管脑脊液中的杀菌效价低于1:2。这一意外发现促使我们评估血清对所选大肠菌群对美洛西林体外敏感性的影响。添加新鲜兔血清可使美洛西林对一株敏感和四株耐药革兰氏阴性肠道杆菌的活性增强许多倍；将血清在56摄氏度加热30分钟可消除这种效应。美洛西林与血清对大肠菌群的这种相互作用应在更多实验感染动物和从接受美洛西林治疗的婴儿获得的标本中进行研究。
