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. 1986 Nov;30(5):645–648. doi: 10.1128/aac.30.5.645

Beta-lactamase-mediated imipenem resistance in Bacteroides fragilis.

G J Cuchural Jr, M H Malamy, F P Tally
PMCID: PMC176506  PMID: 3492173

Abstract

Imipenem has excellent antimicrobial activity owing in part to beta-lactamase stability. We found that only 2 of over 350 Bacteroides fragilis group clinical isolates were resistant to imipenem, with an MIC of more than 16 micrograms/ml. These two isolates from the Tufts Anaerobe Laboratory (TAL) were resistant to all other beta-lactam agents tested. The organisms were able to inactivate imipenem in broth cultures and contained similar beta-lactamases that were able to hydrolyze carbapenems, cephamycins, cephalosporins, and penicillins. The molecular sizes of the beta-lactamases in TAL2480 and TAL3636 were estimated to be 44,000 daltons. The novel beta-lactamase contained Zn2+ as a cofactor. An additional factor contributing to resistance was determined. The outer membranes of these two organisms were found to limit free diffusion of the drugs into the periplasm. This novel beta-lactamase, associated with a barrier to drug permeation, resulted in high-grade beta-lactam drug resistance.

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Selected References

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

  1. Baldwin G. S., Galdes A., Hill H. A., Waley S. G., Abraham E. P. A spectroscopic study of metal ion and ligand binding to beta-lactamase II. J Inorg Biochem. 1980 Nov;13(3):189–204. doi: 10.1016/s0162-0134(00)80068-9. [DOI] [PubMed] [Google Scholar]
  2. Brown J. E., Del Bene V. E., Collins C. D. In vitro activity of N-formimidoyl thienamycin, moxalactam, and other new beta-lactam agents against Bacteroides fragilis: contribution of beta-lactamase to resistance. Antimicrob Agents Chemother. 1981 Feb;19(2):248–252. doi: 10.1128/aac.19.2.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bush K., Freudenberger J. S., Sykes R. B. Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria. Antimicrob Agents Chemother. 1982 Sep;22(3):414–420. doi: 10.1128/aac.22.3.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cuchural G. J., Jr, Tally F. P., Jacobus N. V., Gorbach S. L., Aldridge K., Cleary T., Finegold S. M., Hill G., Iannini P., O'Keefe J. P. Antimicrobial susceptibilities of 1,292 isolates of the Bacteroides fragilis group in the United States: comparison of 1981 with 1982. Antimicrob Agents Chemother. 1984 Aug;26(2):145–148. doi: 10.1128/aac.26.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cuchural G. J., Jr, Tally F. P., Jacobus N. V., Marsh P. K., Mayhew J. W. Cefoxitin inactivation by Bacteroides fragilis. Antimicrob Agents Chemother. 1983 Dec;24(6):936–940. doi: 10.1128/aac.24.6.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Georgopapadakou N. H., Smith S. A., Sykes R. B. Penicillin-binding proteins in Bacteroides fragilis. J Antibiot (Tokyo) 1983 Jul;36(7):907–910. doi: 10.7164/antibiotics.36.907. [DOI] [PubMed] [Google Scholar]
  7. Hill H. A., Sammes P. G., Waley S. G. Active sites of beta-lactamases from Bacillus cereus. Philos Trans R Soc Lond B Biol Sci. 1980 May 16;289(1036):333–344. doi: 10.1098/rstb.1980.0050. [DOI] [PubMed] [Google Scholar]
  8. Marsh P. K., Malamy M. H., Shimell M. J., Tally F. P. Sequence homology of clindamycin resistance determinants in clinical isolates of Bacteroides spp. Antimicrob Agents Chemother. 1983 May;23(5):726–730. doi: 10.1128/aac.23.5.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nikaido H., Vaara M. Molecular basis of bacterial outer membrane permeability. Microbiol Rev. 1985 Mar;49(1):1–32. doi: 10.1128/mr.49.1.1-32.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. O'Callaghan C. H., Morris A., Kirby S. M., Shingler A. H. Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother. 1972 Apr;1(4):283–288. doi: 10.1128/aac.1.4.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Olsson B., Dornbusch K., Nord C. E. Factors contributing to resistance to beta-lactam antibiotics in Bacteroides fragilis. Antimicrob Agents Chemother. 1979 Feb;15(2):263–268. doi: 10.1128/aac.15.2.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Olsson B., Nord C. E., Wadström T. Formation of beta-lactamase in Bacteroides fragilis: cell-bound and extracellular activity. Antimicrob Agents Chemother. 1976 May;9(5):727–735. doi: 10.1128/aac.9.5.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Saino Y., Kobayashi F., Inoue M., Mitsuhashi S. Purification and properties of inducible penicillin beta-lactamase isolated from Pseudomonas maltophilia. Antimicrob Agents Chemother. 1982 Oct;22(4):564–570. doi: 10.1128/aac.22.4.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sato K., Fujii T., Okamoto R., Inoue M., Mitsuhashi S. Biochemical properties of beta-lactamase produced by Flavobacterium odoratum. Antimicrob Agents Chemother. 1985 Apr;27(4):612–614. doi: 10.1128/aac.27.4.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sato K., Matsuura Y., Inoue M., Mitsuhashi S. Properties of a new penicillinase type produced by Bacteroides fragilis. Antimicrob Agents Chemother. 1982 Oct;22(4):579–584. doi: 10.1128/aac.22.4.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tally F. P., Cuchural G. J., Jacobus N. V., Gorbach S. L., Aldridge K. E., Cleary T. J., Finegold S. M., Hill G. B., Iannini P. B., McCloskey R. V. Susceptibility of the Bacteroides fragilis group in the United States in 1981. Antimicrob Agents Chemother. 1983 Apr;23(4):536–540. doi: 10.1128/aac.23.4.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tally F. P., Jacobus N. V., Bartlett J. G., Gorbach S. L. Susceptibility of anaerobes to cefoxitin and other cephalosporins. Antimicrob Agents Chemother. 1975 Feb;7(2):128–132. doi: 10.1128/aac.7.2.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Vu H., Nikaido H. Role of beta-lactam hydrolysis in the mechanism of resistance of a beta-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum beta-lactams. Antimicrob Agents Chemother. 1985 Mar;27(3):393–398. doi: 10.1128/aac.27.3.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Waley S. G. A spectrophotometric assay of beta-lactamase action on penicillins. Biochem J. 1974 Jun;139(3):789–790. doi: 10.1042/bj1390789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Yotsuji A., Minami S., Inoue M., Mitsuhashi S. Properties of novel beta-lactamase produced by Bacteroides fragilis. Antimicrob Agents Chemother. 1983 Dec;24(6):925–929. doi: 10.1128/aac.24.6.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zimmermann W., Rosselet A. Function of the outer membrane of Escherichia coli as a permeability barrier to beta-lactam antibiotics. Antimicrob Agents Chemother. 1977 Sep;12(3):368–372. doi: 10.1128/aac.12.3.368. [DOI] [PMC free article] [PubMed] [Google Scholar]

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