IN-VITRO ASSESSMENT OF THE EFFECT OF CLAVULANIC ACID AT CONCENTRATIONS ACHIEVED IN HUMAN SERUM ON THE BACTERICIDAL ACTIVITY OF AMOXICILLIN AT PHYSIOLOGICAL CONCENTRATIONS AGAINST STAPHYLOCOCCUS-AUREUS - IMPLICATIONS FOR DOSAGE REGIMENS

The effects on Staphylococcus aureus viability and p-lactamase activit y of concentrations that simulated those in human serum after a combin ed dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were st udied in an in vitro pharmacodynamic model. Six hours of preexposure t o concentrations of the amoxicillin-clavulanic acid combination that w ere higher than the amoxicillin-clavulanic acid MIC led to a reduction of the initial inoculum of > 90% and to a Significant decrease of bet a-lactamase activity versus those of the control even from 6 h, when c oncentrations were subinhibitory. The postantibiotic effect and post-b eta-lactamase inhibitor effect contributed to these results.