Skip to main content
Log in

Lack of additive effect between mechanisms of resistance to carbapenems and other beta-lactam agents inPseudomonas aeruginosa

  • Article
  • Published:
European Journal of Clinical Microbiology and Infectious Diseases Aims and scope Submit manuscript

Abstract

Eighty-nine clinical isolates resistant (n=61) or susceptible (n=28) to imipenem and exhibiting the main patterns of susceptibility to other β-lactam agents (wild type pattern, penicillinase pattern, constitutive cephalosporinase pattern) were studied in order to investigate (i) the mechanism of resistance involved and (ii) whether resistance to carbapenems affects the level of resistance to other β-lactam agents and, conversely, if resistance to other β-lactam agents affects the level of resistance to carbapenems. For this purpose, the presence of OprD protein in the cell wall was detected by Western blot and β-lactamase activity by spectrophotometric assay and isoelectric focusing. OprD expression was not detectable in the imipenem-resistant (MIC≥16 μg/ml) strains. It was decreased in half the strains for which MICs of imipenem were 2 to 8 μg/ml and was close to a normal level in the most susceptible strains (MIC ≤1 μg/ml), thus demonstrating a direct correlation between the level of susceptibility to imipenem and the level of OprD expression. No imipenemase activity was detected in imipenem-resistant strains. Synergy between imipenem or meropenem and BRL42715 was observed for all of the strains, demonstrating the role of cephalosporinase in carbapenem resistance. Within each pattern of susceptibility, the mean MICs of β-lactam agents other than carbapenems were similar, whether the strains were susceptible or resistant to imipenem. Conversely, the mean MICs of imipenem or meropenem for either the imipenem-resistant or the imipenem-susceptible strains were similar, regardless of the susceptibility of these strains to the other β-lactam agents. Thus, when several mechanisms of resistance to β-lactam agents are present in the same strain ofPseudomonas aeruginosa, there is no additive effect between these mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Trias J, Nikaido H: Protein D2 channel ofPseudomonas aeruginosa outer membrane has a binding site for basic amino acids and peptides. Journal of Biological Chemistry 1990, 265: 15680–15684.

    PubMed  Google Scholar 

  2. Büsher K-H, Cullmann W, Dick W, Opferkuch W: Imipenem resistance inPseudomonas aeruginosa resulting from diminished expression of an outer membrane protein. Antimicrobial Agents and Chemotherapy 1987, 31: 703–708.

    PubMed  Google Scholar 

  3. Quinn JP, Dudek EJ, Divincenzo CA, Lucks DA, Lerner SA: Emergence of resistance to imipenem during therapy forPseudomonas aeruginosa infections. Journal of Infectious Diseases 1986, 154: 289–294.

    PubMed  Google Scholar 

  4. Trias J, Dufresne J, Levesque RC, Nikaido H: Decreased outer membrane permeability in imipenem-resistant mutants ofPseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 1989, 33: 1201–1206.

    Google Scholar 

  5. Huang H, Hancock REW: Genetic definition of the substrate selectivity of outer membrane porin protein OprD ofPseudomonas aeruginosa. Journal of Bacteriology 1993, 175: 7793–7800.

    PubMed  Google Scholar 

  6. Yoneyama H, Nakae T: Cloning of the protein D2 gene ofPseudomonas aeruginosa and its functional expression in the imipenem-resistant host. FEBS Letters 1991, 283: 177–179.

    PubMed  Google Scholar 

  7. Livermore DM: Interplay of impermeability and chromosomal β-lactamase activity in imipenem-resistantPseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 1992, 36: 2046–2048.

    PubMed  Google Scholar 

  8. Zhou XY, Kitzis MD, Gutmann L: Role of cephalosporinase in carbapenem resistance of clinical isolates ofPseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 1993, 37: 1387–1389.

    PubMed  Google Scholar 

  9. Catchpole CR, Wise R, Thornber D, Andrews JM: In vitro activity of L-627, a new carbapenem. Antimicrobial Agents and Chemotherapy 1992, 36: 1928–1934.

    PubMed  Google Scholar 

  10. Satake S, Yoneyama H, Nakae T: Role of Omp D2 and chromosomal β-lactamase in carbapenem resistance in clinical isolates ofPseudomonas aeruginosa. Journal of Antimicrobial Chemotherapy 1991, 18: 199–207.

    Google Scholar 

  11. Bellido F, Veuthey C, Blaser J, Bauernfeind A, Pechere JC: Novel resistance to imipenem associated with an altered PBP-4 in aPseudomonas aeruginosa clinical isolate. Journal of Antimicrobial Chemotherapy 1990, 25: 57–68.

    PubMed  Google Scholar 

  12. Watanabe M, Iyobe S, Inoue M, Mitsuhashi S: Transferable imipenem resistance inPseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 1991, 35: 147–151.

    PubMed  Google Scholar 

  13. Sanders C, Sanders WE Jr: Emergence of resistance during therapy with the newer β-lactam antibiotics: role of inducible β-lactamase and implications for the future. Reviews of Infectious Diseases 1983, 5: 639–648.

    PubMed  Google Scholar 

  14. Philippon A, Thabaut A, Meyran M, Nevot P: Distribution des bêta-lactamases constitutives chezPseudomonas aeruginosa. La Presse Médicale 1984, 13: 772–776.

    Google Scholar 

  15. Philippon A, Thabaut A, Nevot P:Pseudomonas aeruginosa et beta-lactamines. In: Courvalin P, Goldstein F, Philippon A, Sirot J (ed): L'antibiogramme. MPC VIDEOM, Paris, 1985, p. 103–110.

    Google Scholar 

  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 1951, 193: 265–275.

    PubMed  Google Scholar 

  17. Hancock REW, Carey AM: Outer membrane ofPseudomonas aeruginosa: heat- and 2-mercaptoethanolmodifiable proteins. Journal of Bacteriology 1979, 140: 902–910.

    PubMed  Google Scholar 

  18. Burnette WN: “Western blotting”: electrophoretic transfer of proteins from SDS-polyacrylamide gels to unmodified nitrocellulose and radio-graphic detection with antibody and radioiodinated protein A. Analytical Biochemistry 1981, 112: 195–203.

    PubMed  Google Scholar 

  19. Trias J, Nikaido H: Outer membrane protein D2 catalyzes facilitated diffusion of carbapenems and penems through the outer membrane ofPseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 1990, 34: 52–57.

    PubMed  Google Scholar 

  20. Leary JJ, Brigati DJ, Ward DC: Rapid and sensitive colorimetric method of visualizing biotin-labeled DNA probes hybridized to DNA or RNA immobilized on nitrocellulose bioblots. Proceedings of the National Academy of Sciences of the USA 1983, 80: 4045–4049.

    PubMed  Google Scholar 

  21. Saino Y, Kobayashi F, Inoue M, Mitsuhashi S: Purification and properties of inductible penicillin β-lactamase isolated fromPseudomonas maltophilia. Antimicrobial Agents and Chemotherapy 1982, 22: 564–570.

    PubMed  Google Scholar 

  22. Sanders CC, Sanders WE Jr, Goering RV: In vitro antagonism of beta-lactam antibiotics by cefoxitin. Antimicrobial Agents and Chemotherapy 1982, 21: 968–975.

    PubMed  Google Scholar 

  23. Nikaido H, Nikaido K, Harayama S: Identification and characterization of porins inPseudomonas aeruginosa. Journal of Biological Chemistry 1991, 266: 770–779.

    PubMed  Google Scholar 

  24. Trias J, Nikaido H: Diffusion of antibiotics via specific pathways across the outer membrane ofPseudomonas aeruginosa. In: Silver S, Chakrabarty AM, Iglewski B, Kaplan S (ed):Pseudomonas: biotransformation, pathogenesis, and evolving biotechnology. American Society for Microbiology, Washington, DC, 1990, p. 319–327.

    Google Scholar 

  25. Livermore DM: Carbapenemases. Journal of Antimicrobial Chemotherapy 1992, 29: 609–616.

    PubMed  Google Scholar 

  26. Nordmann P, Mariotte S, Naas T, Labia R, Nicolas MH: Biochemical properties of a carbapenem-hydrolyzing β-lactamase fromEnterobacter cloacae and cloning of the gene intoEscherichia coli. Antimicrobial Agents and Chemotherapy 1993, 37: 939–946.

    PubMed  Google Scholar 

  27. Vu H, Nikaido H: Role of β-lactam hydrolysis in the mechanism of resistance of a β-lactamase-constitutiveEnterobacter cloacae strain to expanded-spectrum β-lactams. Antimicrobial Agents and Chemotherapy 1985, 27: 393–398.

    PubMed  Google Scholar 

  28. Lee EH, Nicolas MH, Kitzis MD, Pialoux G, Collatz E, Gutmann L: Association of two resistance mechanisms in a clinical isolate ofEnterobacter cloacae with high level resistance to imipenem. Antimicrobial Agents and Chemotherapy 1991, 35: 1093–1098.

    PubMed  Google Scholar 

  29. Bush K: Classification of β-lactamases: groups 2c, 2d, 2e, 3, and 4. Antimicrobial Agents and Chemotherapy 1989, 33: 271–276.

    PubMed  Google Scholar 

  30. Jarlier V, Nicolas MH, Fournier G, Philippon A: Extended broad-spectrum β-lactamases conferring transferable resistance to newer β-lactam agents inEnterobacteriaceae: hospital prevalence and susceptibility patterns. Reviews of Infectious Diseases 1988, 10: 867–878.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dib, C., Trias, J. & Jarlier, V. Lack of additive effect between mechanisms of resistance to carbapenems and other beta-lactam agents inPseudomonas aeruginosa . Eur. J. Clin. Microbiol. Infect. Dis. 14, 979–986 (1995). https://doi.org/10.1007/BF01691380

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01691380

Keywords

Navigation