β-内酰胺酶抑制剂舒巴坦与氨苄西林联用的体内外抗菌作用研究

The in Vitro and in Vivo Antibacterial Activity of β-lactamase Inhibitor Sulbactam Plus Ampicillin

试验观察了β 内酰胺酶抑制剂舒巴坦与氨苄西林联用的体内外协同抗菌作用。结果表明 :氨苄西林与舒巴坦联用对 5个标准菌株的抗菌活性与氨苄西林相似 ,对除绿脓杆菌外的 6株临床分离菌株的体外抗菌活性较显著高于氨苄西林。临床分离菌株均可产生 β 内酰胺酶并可不同程度的水解氨苄西林 ,在不加入舒巴坦时 ,β 内酰胺酶对氨苄西林的水解率为 5 7 6 4%～ 10 0 % ,加入舒巴坦时 ,β 内酰胺酶对氨苄西林的水解率降低。舒巴坦对临床分离菌株产生的 5种 β 内酰胺酶均有抑制作用 ,在 1μg/ml时的抑制率为 9 35 %～ 6 7 2 0 % ,10 μg/ml时为 5 0 %～93 19% ,显示出明显的抑酶保护作用。氨苄西林与舒巴坦联用对氨苄西林耐药菌株引起的鸡白痢有明显的治疗效果 ,按 5mg/kg肌注的治愈率为 91 18% ,显著高于氨苄西林混饮 ,与舒他西林相似。提示二者联用体内体外均有协同抗菌作用 ,值得进一步研究。

The in vitro and in vivo synergistic antibacterial activity of β-lactamase inhibitor sulbatam with ampicillin was investigated.Results indicated that sulbatam with ampicillin had potent activity against 11 strains of avian pathogens except P aeruginosa,the combination in vitro had similar antibacterial activities against 5 strains of avian standard pathogens and much better activity against 6 isolates compared with ampicillin.All tested isolates ampicillin-resistant were found to be able to produce β-lactamase.Ampicillin could be hydrolyzed in various degrees by all β-lactamase tested.The hydrolysis rates were 57.64%～100%,and decreased when the inhibitor was added.Sulbatam had definite inhibition on 5 β-lactamases produced by clinical isolates,at concentration of 1 μg/ml and 10 μg/ml,inhibitory rates of sulbatam were 9.35%～67.20% and 50%～93.19% respectively.Above experiment results revealed that sulbatam possess good inhibitory actions on the β-lactamases.According to treatment trial,the combination of sulbatam with ampicillin is effective in controlling avian S.pullorum infection when administered intramuscularly.Following treatment at a dose 5 mg/kg twice daily for 4 successive days,the cure rate of sulbatam with ampicillin against artificially infected pollorum disease in chickens were 91.18%,the efficacy was same as that of sultacillin,significantly higher than that of ampicillin alone.Our investigation showed that the combination of sulbatam with ampicillin possessed a great synergism in the in vitro and in vivo antibacterial action,which is worth of further investigation.