Lapointe J R, Lavallée C
J Antimicrob Chemother. 1987 Jan;19(1):49-58. doi: 10.1093/jac/19.1.49.
We studied the specific beta-lactamase inhibitory activity of clavulanic acid in association with amoxycillin against 132 beta-lactamase producing Haemophilus isolates. Inhibitory synergy between amoxycillin and clavulanic acid (ratio 2:1) was found in 131/132, partial synergy or antagonism in none; bactericidal synergy was found in 124/131, partial synergy in 4 and antagonism in 1. In comparison, inhibitory synergy between trimethoprim and sulphamethoxazole (ratio 1:19) was found in only 39/104 beta-lactamase positive strains, partial synergy in 42 and antagonism in 3 and bactericidal synergy in 18/104, partial synergy in 8 and antagonism in 3. The amoxycillin-clavulanic acid combination expressed significantly (P less than 0.001) more frequent synergy, at both inhibitory and bactericidal levels, than the trimethoprim-sulphamethoxazole combination. The synergy of amoxycillin-clavulanic acid resulted in a significant decrease of MIC90 (greater than or equal to 32.0-2.0 mg/l) and MBC90 (greater than or equal to 32.0-4.0 mg/l) of amoxycillin; the synergy of trimethoprim-sulphamethoxazole resulted in a significant decrease of MIC90 (8.0-2.0 mg/l) of trimethoprim but did not change MBC90. The amoxycillin-clavulanic acid combination was also more active than cefaclor or erythromycin alone against the 132 beta-lactamase producing strains.
我们研究了克拉维酸与阿莫西林联合对132株产β-内酰胺酶的嗜血杆菌分离株的特异性β-内酰胺酶抑制活性。在132株中，131株发现阿莫西林与克拉维酸（比例2:1）之间有抑制协同作用，无部分协同作用或拮抗作用；在131株中有124株发现杀菌协同作用，4株有部分协同作用，1株有拮抗作用。相比之下，在104株β-内酰胺酶阳性菌株中，仅39株发现甲氧苄啶与磺胺甲恶唑（比例1:19）之间有抑制协同作用，42株有部分协同作用，3株有拮抗作用，在104株中有18株发现杀菌协同作用，8株有部分协同作用，3株有拮抗作用。阿莫西林-克拉维酸组合在抑制和杀菌水平上的协同作用均显著（P<0.001）高于甲氧苄啶-磺胺甲恶唑组合。阿莫西林-克拉维酸的协同作用导致阿莫西林的MIC90（≥32.0 - 2.0mg/L）和MBC90（≥32.0 - 4.0mg/L）显著降低；甲氧苄啶-磺胺甲恶唑的协同作用导致甲氧苄啶的MIC90（8.0 - 2.0mg/L）显著降低，但未改变MBC90。阿莫西林-克拉维酸组合对132株产β-内酰胺酶菌株的活性也高于单独使用头孢克洛或红霉素。
