Chavanet P, Collin F, Muggeo E, Gagelin B, Chassin P, Kosmidis V, Bernard A, Kistermann J P, Portier H
Department of Infectious Diseases, CHRU Hopital du Bocage, Dijon, France.
J Antimicrob Chemother. 1993 Jan;31(1):129-38. doi: 10.1093/jac/31.1.129.
This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE). MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L. In rabbits treated with a single-dose i.v. regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001). Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug. From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase-positive and methicillin-resistant S. epidermidis infection; some enzyme-resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S. epidermidis infection; the combination of co-amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model.
本研究比较了阿莫西林克拉维酸、万古霉素和替考拉宁分别联合或不联合奈替米星或阿米卡星,用于治疗由临床分离的产β-内酰胺酶、耐甲氧西林和耐庆大霉素的表皮葡萄球菌菌株(MGRSE)引起的兔实验性皮下纤维蛋白凝块感染。该菌株的最低抑菌浓度(MIC,mg/L)为:苯唑西林125、庆大霉素32、万古霉素4、替考拉宁8、奈替米星1、阿米卡星4、阿莫西林64加克拉维酸2mg/L。采用单剂量静脉注射方案(奈替米星8mg/kg、阿米卡星20mg/kg、万古霉素30mg/kg、替考拉宁15mg/kg、阿莫西林克拉维酸150 - 30mg/kg)治疗的兔,无论使用何种联合用药,给药后24小时的细菌计数均降低(方差分析,P≤0.001)。各治疗方案按疗效从高到低的统计学分类如下:阿莫西林克拉维酸联合奈替米星>单独使用万古霉素或万古霉素联合奈替米星或阿米卡星、替考拉宁联合奈替米星>单独使用奈替米星和阿莫西林克拉维酸>替考拉宁或阿莫西林克拉维酸联合阿米卡星、单独使用替考拉宁>阿米卡星>未用药。从这些结果得出结论:阿莫西林克拉维酸可用于治疗产β-内酰胺酶和耐甲氧西林的表皮葡萄球菌感染;对于耐庆大霉素但对奈替米星/阿米卡星敏感的表皮葡萄球菌感染,可考虑使用一些耐酶氨基糖苷类药物;在该动物模型中,阿莫西林克拉维酸与奈替米星联合具有协同作用,且比万古霉素杀菌更快。