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阿莫西林克拉维酸与奈替米星联合应用对兔实验性耐甲氧西林和耐庆大霉素表皮葡萄球菌感染的体内活性。

The in-vivo activity of co-amoxiclav with netilmicin against experimental methicillin and gentamicin resistant Staphylococcus epidermidis infection in rabbits.

作者信息

Chavanet P, Collin F, Muggeo E, Gagelin B, Chassin P, Kosmidis V, Bernard A, Kistermann J P, Portier H

机构信息

Department of Infectious Diseases, CHRU Hopital du Bocage, Dijon, France.

出版信息

J Antimicrob Chemother. 1993 Jan;31(1):129-38. doi: 10.1093/jac/31.1.129.

Abstract

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.

摘要

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。

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