Schimpff S C, Drusano G L, Standiford H C
Eur J Clin Microbiol. 1986 Feb;5(1):71-8. doi: 10.1007/BF02013473.
A review is given of work utilizing the serum bactericidal test for preclinical evaluation of agents considered for treatment of gram-negative sepsis among neutropenic cancer patients. Following a description of the methodology of the two major groups, the results of the various antibiotic trials are summarized. First the extended-spectrum cephalosporins (cefotaxime, cefoperazone, and moxalactam) were tested and found to be, at best, of limited value as single agents for Pseudomonas aeruginosa, a common pathogen of neutropenic cancer patients. When the extended-spectrum penicillins became available, the serum bactericidal levels in volunteers of mezlocillin and piperacillin were compared alone or in combination with an aminoglycoside to ticarcillin with or without aminoglycoside against the same organisms. Piperacillin proved to be most effective followed by mezlocillin and then ticarcillin; in each case the addition of the aminoglycoside improved serum bactericidal activity. Recent studies suggest that imipenem alone is as active as the combination of a broad-spectrum penicillin plus an aminoglycoside and is worthy of a carefully controlled clinical trial. These types of volunteer-based evaluations of the serum bactericidal activity of new compounds may help predict useful clinical approaches for the future.
本文综述了利用血清杀菌试验对拟用于治疗中性粒细胞减少癌症患者革兰氏阴性菌败血症的药物进行临床前评估的相关研究。在描述了两大主要研究组的方法后，总结了各种抗生素试验的结果。首先对广谱头孢菌素（头孢噻肟、头孢哌酮和拉氧头孢）进行了测试，发现其作为单一药物治疗中性粒细胞减少癌症患者的常见病原体铜绿假单胞菌时，效果极为有限。当广谱青霉素问世后，将美洛西林和哌拉西林在志愿者中的血清杀菌水平单独或与氨基糖苷类药物联合使用时，与替卡西林单独或与氨基糖苷类药物联合使用时针对相同病原体的情况进行了比较。结果表明，哌拉西林最为有效，其次是美洛西林，然后是替卡西林；在每种情况下，添加氨基糖苷类药物均可提高血清杀菌活性。最近的研究表明，亚胺培南单独使用时的活性与广谱青霉素加氨基糖苷类药物联合使用时相当，值得进行一项严格对照的临床试验。这些基于志愿者的新化合物血清杀菌活性评估类型可能有助于预测未来有用的临床治疗方法。
