Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1982 Jun;21(6):968–975. doi: 10.1128/aac.21.6.968

In vitro antagonism of beta-lactam antibiotics by cefoxitin.

C C Sanders, W E Sanders Jr, R V Goering
PMCID: PMC182054  PMID: 6981376

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, 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.

Full text

PDF
968

Images in this article

972Image
on p.972
973Image
on p.973

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Birnbaum J., Stapley E. O., Miller A. K., Wallick H., Hendlin D., Woodruff H. B. Cefoxitin, a semi-synthetic cephamycin: a microbiological overview. J Antimicrob Chemother. 1978 Jul;4(B):15–32. doi: 10.1093/jac/4.suppl_b.15. [DOI] [PubMed] [Google Scholar]
  2. Chattopadhyay B., Hall I. Antagonism between cefoxitin and cefuroxime. J Antimicrob Chemother. 1979 Jul;5(4):490–491. doi: 10.1093/jac/5.4.490. [DOI] [PubMed] [Google Scholar]
  3. Curtis N. A., Orr D., Ross G. W., Boulton M. G. Competition of beta-lactam antibiotics for the penicillin-binding proteins of Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella aerogenes, Proteus rettgeri, and Escherichia coli: comparison with antibacterial activity and effects upon bacterial morphology. Antimicrob Agents Chemother. 1979 Sep;16(3):325–328. doi: 10.1128/aac.16.3.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fu K. P., Neu H. C. The role of inducible beta-lactamases in the antagonism seen with certain cephalosporin combinations. J Antimicrob Chemother. 1981 Jan;7(1):104–107. doi: 10.1093/jac/7.1.104. [DOI] [PubMed] [Google Scholar]
  5. Fu K. P., Neu H. C. beta-lactamase stability of HR 756, a novel cephalosporin, compared to that of cefuroxime and cefoxitin. Antimicrob Agents Chemother. 1978 Sep;14(3):322–326. doi: 10.1128/aac.14.3.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldner M., Glass D. G., Fleming P. C. Characteristics of Aerobacter beta-lactamase. Can J Microbiol. 1968 Feb;14(2):139–145. doi: 10.1139/m68-023. [DOI] [PubMed] [Google Scholar]
  7. Goldner M., Glass D. G., Fleming P. C. Spontaneous mutant with loss of beta-lactamase in Aerobacter cloacae. J Bacteriol. 1969 Feb;97(2):961–961. doi: 10.1128/jb.97.2.961-.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grimm H. Bakteriologische Untersuchungen zum Antagonismus zwischen Acylureidopenicillinen und Cephalosporinen. Arzneimittelforschung. 1980;30(6):999–1000. [PubMed] [Google Scholar]
  9. Hennessey T. D. Inducible beta-lactamase in Enterobacter. J Gen Microbiol. 1967 Nov;49(2):277–285. doi: 10.1099/00221287-49-2-277. [DOI] [PubMed] [Google Scholar]
  10. Kammer W., Neuhaus B. In-vitro-Antagonismus von Cefoxitin und Azlozillin im Agar-Diffusionstest. Offentl Gesundheitswes. 1978 Sep;40(9):621–621. [PubMed] [Google Scholar]
  11. King A., Shannon K., Phillips I. In vitro antibacterial activity and susceptibility of cefsulodin, an antipseudomonal cephalosporin, to beta-lactamases. Antimicrob Agents Chemother. 1980 Feb;17(2):165–169. doi: 10.1128/aac.17.2.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Komatsu Y., Nishikawa T. Moxalactam (6059-S), a new 1-oxa-beta-lactam: binding affinity for penicillin-binding proteins of Escherichia coli K-12. Antimicrob Agents Chemother. 1980 Mar;17(3):316–321. doi: 10.1128/aac.17.3.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kuck N. A., Testa R. T., Forbes M. In vitro and in vivo antibacterial effects of combinations of beta-lactam antibiotics. Antimicrob Agents Chemother. 1981 Apr;19(4):634–638. doi: 10.1128/aac.19.4.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Onishi H. R., Daoust D. R., Zimmerman S. B., Hendlin D., Stapley E. O. Cefoxitin, a semisynthetic cephamycin antibiotic: resistance to beta-lactamase inactivation. Antimicrob Agents Chemother. 1974 Jan;5(1):38–48. doi: 10.1128/aac.5.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. RIchmond M. H. The semi-synthetic thienamycin derivative MK0787 and its properties with respect to a range of beta-lactamases from clinically relevant bacterial species. J Antimicrob Chemother. 1981 Mar;7(3):279–285. doi: 10.1093/jac/7.3.279. [DOI] [PubMed] [Google Scholar]
  16. Richmond M. H. In vitro studies with mecillinam on Escherichia coli and Pseudomonas aeruginosa. J Antimicrob Chemother. 1977 Jul;3 (Suppl B):29–39. doi: 10.1093/jac/3.suppl_b.29. [DOI] [PubMed] [Google Scholar]
  17. Richmond M. H. The beta-lactamase stability of a novel beta-lactam antibiotic containing a 7 alpha-methoxyoxacephem nucleus. J Antimicrob Chemother. 1980 Jul;6(4):445–453. doi: 10.1093/jac/6.4.445. [DOI] [PubMed] [Google Scholar]
  18. Sabath L. D., Jago M., Abraham E. P. Cephalosporinase and penicillinase activities of a beta-lactamase from Pseudomonas pyocyanea. Biochem J. 1965 Sep;96(3):739–752. doi: 10.1042/bj0960739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sanders C. C., Sanders W. E., Jr Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases. Antimicrob Agents Chemother. 1979 Jun;15(6):792–797. doi: 10.1128/aac.15.6.792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Spratt B. G. Properties of the penicillin-binding proteins of Escherichia coli K12,. Eur J Biochem. 1977 Jan;72(2):341–352. doi: 10.1111/j.1432-1033.1977.tb11258.x. [DOI] [PubMed] [Google Scholar]
  21. Sykes R. B., Matthew M. The beta-lactamases of gram-negative bacteria and their role in resistance to beta-lactam antibiotics. J Antimicrob Chemother. 1976 Jun;2(2):115–157. doi: 10.1093/jac/2.2.115. [DOI] [PubMed] [Google Scholar]
  22. Takahashi I., Sawai T., Ando T., Yamagishi S. Cefoxitin resistance by a chromosomal cephalosporinase in Escherichia coli. J Antibiot (Tokyo) 1980 Sep;33(9):1037–1042. doi: 10.7164/antibiotics.33.1037. [DOI] [PubMed] [Google Scholar]
  23. Tomasz A. From penicillin-binding proteins to the lysis and death of bacteria: a 1979 view. Rev Infect Dis. 1979 May-Jun;1(3):434–467. doi: 10.1093/clinids/1.3.434. [DOI] [PubMed] [Google Scholar]
  24. Waterworth P. M., Emmerson A. M. Dissociated resistance among cephalosporins. Antimicrob Agents Chemother. 1979 Apr;15(4):497–503. doi: 10.1128/aac.15.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yamamoto T., Yokota T. Beta-lactamase-directed barrier for penicillins of Escherichia coli carrying R plasmids. Antimicrob Agents Chemother. 1977 Jun;11(6):936–940. doi: 10.1128/aac.11.6.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zimmermann W. Penetration of beta-lactam antibiotics into their target enzymes in Pseudomonas aeruginosa: comparison of a highly sensitive mutant with its parent strain. Antimicrob Agents Chemother. 1980 Jul;18(1):94–100. doi: 10.1128/aac.18.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES