Farrar W E, Newsome J K
Antimicrob Agents Chemother. 1973 Aug;4(2):109-14. doi: 10.1128/AAC.4.2.109.
These studies were undertaken to elucidate further the mechanism of synergism of pairs of beta-lactam antibiotics on beta-lactamase-producing gram-negative bacilli. Three strains of gram-negative bacilli which elaborate beta-lactamase enzymes with widely differing properties were employed. The antibacterial effects of beta-lactam antibiotics, singly and in combination, on the three organisms investigated were exactly those which would have been predicted on the basis of the enzymological properties of the beta-lactamases elaborated by these organisms. The findings thus support the hypothesis that the synergistic antibacterial effects of combinations of beta-lactam antibiotics on these organisms were due to inhibition of the enzyme by one of the agents and killing of the organism by the other, which was protected from enzymatic hydrolysis, rather than the alternative possibility that the synergistic effects were due simply to the combined antibacterial actions of the two drugs.
开展这些研究是为了进一步阐明β-内酰胺类抗生素对产β-内酰胺酶革兰氏阴性杆菌的协同作用机制。使用了三株革兰氏阴性杆菌，它们产生的β-内酰胺酶具有广泛不同的特性。单独使用及联合使用β-内酰胺类抗生素对所研究的三种微生物的抗菌作用，恰好是基于这些微生物所产生的β-内酰胺酶的酶学特性所预测的结果。因此，这些发现支持了这样一种假说，即β-内酰胺类抗生素组合对这些微生物的协同抗菌作用是由于其中一种药物抑制了酶，而另一种药物杀死了免受酶水解的微生物，而不是协同作用仅仅是由于两种药物联合抗菌作用的另一种可能性。
