Li R C, Lee S W, Kong C H
Department of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin.
J Antimicrob Chemother. 1997 Jul;40(1):39-45. doi: 10.1093/jac/40.1.39.
Theoretically, if the postantibiotic effect (PAE) reflects the duration of cellular recovery, then the extent of cellular damage inflicted on bacteria by an antibiotic, as suggested by the degree of bactericidal activity, should reflect the length of PAE; this is especially true if binding of the antibiotic to bacterial receptors is irreversible. To test this hypothesis, correlation between PAEs and bactericidal rate constants measured simultaneously at various antibiotic concentrations was examined for five antibiotic-bacterium combinations. Each of the five antibiotics used, i.e. tobramycin, ciprofloxacin, dicloxacillin, trimethoprim and tetracycline, has a different mechanism of action: the first three bind irreversibly to bacterial receptors, while trimethoprim and tetracycline bind reversibly. Both PAE and bactericidal activity increased nonlinearly with concentrations in a saturable manner for all the combinations studied. Linear least-square regression analyses showed strong correlations (P < 0.01) between the two responses for individual combinations. Such a linear relationship also extended, with good correlation (P < 0.05), across the five combinations when individual maximal bactericidal rate constants and PAEs were considered separately. These observations suggest that cellular recovery from nonlethal damage following antibiotic exposure may be a major determinant of PAE.
理论上，如果抗生素后效应（PAE）反映细胞恢复的持续时间，那么如杀菌活性程度所表明的，抗生素对细菌造成的细胞损伤程度应反映PAE的时长；如果抗生素与细菌受体的结合是不可逆的，情况尤其如此。为了验证这一假设，针对五种抗生素 - 细菌组合，研究了在不同抗生素浓度下同时测得的PAE与杀菌速率常数之间的相关性。所使用的五种抗生素，即妥布霉素、环丙沙星、双氯西林、甲氧苄啶和四环素，各自具有不同的作用机制：前三种抗生素与细菌受体不可逆结合，而甲氧苄啶和四环素可逆结合。对于所有研究的组合，PAE和杀菌活性均随浓度以饱和方式呈非线性增加。线性最小二乘回归分析表明，各个组合的两种反应之间存在强相关性（P < 0.01）。当分别考虑各个最大杀菌速率常数和PAE时，这种线性关系在五种组合之间也具有良好的相关性（P < 0.05）。这些观察结果表明，抗生素暴露后细胞从非致死性损伤中的恢复可能是PAE的主要决定因素。
