Cullmann W, Binder S, Stieglitz M
Immun Infekt. 1987 May;15(3):103-9.
Both inhibitors clavulanic acid and sulbactam exhibit high affinity (Ki-values less than 10(-6) mol/l) to the beta-lactamases of gram-negative bacteria with predominant penicillinase activity and lowered affinity to enzymes with cephalosporinase activity (above all clavulanic acid). As compared to sulbactam there was a stronger synergism of clavulanic acid with ampicillin or mezlocillin in those isolates producing either a plasmid-mediated or a chromosomally-mediated penicillinase. In beta-lactamase-overproducing Klebsiella ssp. variants both inhibitors could protect neither ampicillin nor mezlocillin from breakdown-independent of the synergy observed in the corresponding wild-type strains. Moreover, there was a marked synergism between mezlocillin (but not ampicillin) and sulbactam in beta-lactamase-overproducing Enterobacter cloacae variants. There was no strong relation between the amount of enzyme produced and the resulting synergy between inhibitor and antibiotic among clinical isolates. These observations agree with the results obtained for routinely performed susceptibility testing of amoxycillin/clavulanic acid and ampicillin/sulbactam.
克拉维酸和舒巴坦这两种抑制剂对具有主要青霉素酶活性的革兰氏阴性菌的β-内酰胺酶均表现出高亲和力（Ki值小于10^(-6) mol/l），而对具有头孢菌素酶活性的酶（尤其是克拉维酸）的亲和力较低。与舒巴坦相比，在产生质粒介导或染色体介导的青霉素酶的分离株中，克拉维酸与氨苄西林或美洛西林具有更强的协同作用。在产β-内酰胺酶过量的克雷伯菌属变种中，两种抑制剂均无法保护氨苄西林或美洛西林不被分解，这与在相应野生型菌株中观察到的协同作用无关。此外，在产β-内酰胺酶过量的阴沟肠杆菌变种中，美洛西林（而非氨苄西林）与舒巴坦之间存在明显的协同作用。在临床分离株中，产生的酶量与抑制剂和抗生素之间产生的协同作用之间没有密切关系。这些观察结果与阿莫西林/克拉维酸和氨苄西林/舒巴坦常规药敏试验的结果一致。
