Évaluation in vitro de l'activité de deux bêtalactamines sur le métabolisme oxydatif de granulocytes neutrophiles

Abstract

The aim was to evaluate the in vitro effects of amoxicillin and its combination with clavulanic acid, two beta-lactams intravenously injected, on the oxidative metabolism of polymorphonuclear neutrophils. These cells play the major role in the "respiratory burst" as they produce superoxide anion to kill the infectious agent. An activation of this process by the injected antibiotics could enhance the bactericidal action or explain some of adverse effects. Two models were used to estimate the O(2)(-) amounts produced in the presence of the antimicrobial agents. In the cellular model, O(2)(-) was generated by neutrophils artificially stimulated or not (separated by a gradient centrifugation through Histopaque 1077). In the acellular model, O(2)(-) was produced by the xanthine-xanthine oxidase system. O(2)(-) was measured by spectrophotometry using the ferricytochrome C reduction. The O(2)(-) production by polymorphonuclear neutrophils was increased when both antibiotics were added to the reaction mixture. A significant activation of the cell oxidative metabolism was observed with amoxicillin using various stimulating agents, that was higher without stimulation and lower when amoxicillin and clavulanic acid were associated. Amoxicillin could either activate polymorphonuclear neutrophils NADPH-oxidase or cause its activation by a membrane effect, or interfere with the zymosan activation way. It could then be supposed that this antimicrobial agent intensified the bactericidal effects.