Antibacterial antagonism of beta-lactam antibiotics in experimental infections.

In vitro, 5 micrograms/ml of cefoxitin induced the highest beta-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 beta-lactam, 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 micrograms/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.