In vitro antagonism of beta-lactam antibiotics by cefoxitin.
We assessed the extent and mechanisms of antagonism of beta-lactam antibiotics by cefoxitin. In tests with 41 gram-negative isolates, cefoxitin antagonized cephalothin, cefamandole, cefsulodin, cefotaxime, moxalactam, ampicillin, carbenicillin, piperacillin, mezlocillin, and azlocillin, but not cephalexin, mecillinam, or N-formimidoyl thienamycin. The extent of antagonism varied with the beta-lactam and genus studied. However, antagonism occurred most often with strains possessing inducible cephalosporinases. Antagonism of cephalothin and cefamandole correlated closely with the induction of beta-lactamases capable of inactivating these drugs. Although antagonism of the remaining drugs occurred more often with strains possessing inducible beta-lactamases, these enzymes did not inactivate the drugs. Morphological studies revealed that cefoxitin inhibited filamentation and lysis produced by various beta-lactam drugs. Results of this investigation suggest that cefoxitin antagonizes beta-lactams via (i) induction of drug-inactivating beta-lactamases, and (ii) the induction of beta-lactamases that cannot inactivate the drug but serve as barriers against access to target proteins. This barrier appears most efficient for drugs that bind to penicillin-binding proteins 1 and 3.
D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D002440:Cefoxitin / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000037:antagonists & inhibitors
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002440:Cefoxitin; D001618:beta-Lactamases