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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001431:Bacteriological Techniques; D002439:Cefotaxime / Q000037:antagonists & inhibitors*; D002440:Cefoxitin / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004347:Drug Interactions; D004790:Enzyme Induction; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D011919:Rats, Inbred Strains; D012706:Serratia marcescens / Q000187:drug effects / Q000201:enzymology; D001618:beta-Lactamases / Q000096:biosynthesis / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002440:Cefoxitin; D001618:beta-Lactamases; D002439:Cefotaxime