Satta G, Cornaglia G, Canepari P, Pompei R
Istituto di Microbiologia dell'Università di Siena.
Drugs. 1988;35 Suppl 2:35-40. doi: 10.2165/00003495-198800352-00009.
In previous studies on Streptococcus faecium we proposed that the minimum beta-lactam concentration killing 99.9% of a bacterial population within 3 hours be defined as the minimum directly bactericidal concentration (MDBC) of that drug. In the present study we first evaluated the kinetics of cellular killing by various beta-lactams as related to penicillin-binding-protein (PBP) binding in Escherichia coli DC2, a hyperpermeable mutant. We concluded that in E. coli the MDBC for beta-lactams coincides with the minimum concentration capable of saturating PBPs 1b, 2 and 3. Of the antibacterial drugs we studied, cefsulodin, mecillinam and aztreonam had a much greater affinity for one essential PBP (PBP 1b, 2 and 3, respectively) than for all others, whereas cefotaxime had close affinities for all the above PBPs. MDBC values of greater than 500, 500, greater than 50, 10 and 1.5 mg/L were obtained for cefsulodin, mecillinam, aztreonam, ampicillin and cefotaxime, respectively. On the basis of the pharmacokinetic properties of these drugs, our results indicate that mecillinam, ampicillin and cefsulodin may be bactericidal in urine but not at other body sites; aztreonam is probably bactericidal in urine and blood, but not elsewhere; and cefotaxime is bactericidal in all the biological fluids we studied.
在之前关于粪肠球菌的研究中，我们提议将在3小时内杀死99.9%细菌群体的最低β-内酰胺浓度定义为该药物的最低直接杀菌浓度（MDBC）。在本研究中，我们首先评估了各种β-内酰胺类药物对超通透突变体大肠杆菌DC2中细胞杀伤的动力学，及其与青霉素结合蛋白（PBP）结合的关系。我们得出结论，在大肠杆菌中，β-内酰胺类药物的MDBC与能够饱和PBP 1b、2和3的最低浓度一致。在我们研究的抗菌药物中，头孢磺啶、美西林和氨曲南对一种必需的PBP（分别为PBP 1b、2和3）的亲和力比对所有其他PBP的亲和力大得多，而头孢噻肟对上述所有PBP的亲和力相近。头孢磺啶、美西林、氨曲南、氨苄西林和头孢噻肟的MDBC值分别大于500、500、大于50、10和1.5mg/L。根据这些药物的药代动力学特性，我们的结果表明，美西林、氨苄西林和头孢磺啶可能在尿液中具有杀菌作用，但在身体其他部位则不然；氨曲南可能在尿液和血液中具有杀菌作用，但在其他部位则不然；而头孢噻肟在我们研究的所有生物体液中均具有杀菌作用。
