Antibacterial Antagonism of β-Lactam Antibiotics in Experimental Infections

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Abstract
In vitro, 5 μg/ml of cefoxitin induced the highest β-lactamase activity in Serratia marcescens TMS22, and the drug at this optimal dose required 2 h to increase the enzyme activity. The increasing enzyme activity was found to decline rapidly after the enzyme inducer effect was lost. When antagonism of cefoxitin against another β-lactarn, cefotaxime, was examined in infected granuloma pouch of rats, cefoxitin antagonized the antibacterial activity of cefotaxime administered at 4 and 6 h after cefoxitin (cefoxitin levels in pouch exudate were around 5 μg/ml). The antagonism of an enzyme inducer and another antibiotic may be prevented by administering the non-enzyme inducer before the enzyme inducer exerts its inducer effect or after the enzyme inducer level decreases to an ineffective one.