In vitro antagonism of beta-lactam antibiotics by cefoxitin

C. C. Sanders, W. E. Sanders, Richard V. Goering

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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, cefotazime, moxalactam, ampicillin, carbenicillin, piperacillin, mezlocillin, and azlocillin, but not caphalexin, mecillinam, or N-formimidoyl thienamycin. The extent of antagonism varied with the betalactam and genus studied. However, antagonism occurred most often with strains possessing inducible cephalosporinases. Antagonism of cephalothin and cafamandole 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.

Original languageEnglish
Pages (from-to)968-975
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume21
Issue number6
StatePublished - 1982

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Cefoxitin
beta-Lactams
beta-Lactamases
Anti-Bacterial Agents
Pharmaceutical Preparations
Penicillin-Binding Proteins
Cephalothin
Drug Antagonism
Amdinocillin
Cefsulodin
Azlocillin
Mezlocillin
Cefamandole
Moxalactam
Carbenicillin
Piperacillin
Ampicillin
In Vitro Techniques
Enzymes
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

In vitro antagonism of beta-lactam antibiotics by cefoxitin. / Sanders, C. C.; Sanders, W. E.; Goering, Richard V.

In: Antimicrobial Agents and Chemotherapy, Vol. 21, No. 6, 1982, p. 968-975.

Research output: Contribution to journalArticle

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