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Related Experiment Videos

Clavulanate and beta-lactamase induction.

D M Livermore1, M Akova, P J Wu

  • 1Department of Medical Microbiology, London Hospital Medical College, UK.

The Journal of Antimicrobial Chemotherapy
|November 1, 1989
PubMed
Summary
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Clavulanate can antagonize ticarcillin in some bacteria by inducing beta-lactamase enzymes. This antagonism is usually transient and not clinically significant, except in specific Enterobacter cloacae and Morganella morganii strains.

Area of Science:

  • Microbiology
  • Pharmacology
  • Antimicrobial Resistance

Background:

  • Beta-lactamase enzymes, particularly inducible Class I beta-lactamases, pose a challenge in treating bacterial infections.
  • Concerns exist regarding the potential antagonistic effect of clavulanate on ticarcillin activity against bacteria with inducible beta-lactamases.

Purpose of the Study:

  • To investigate the mechanism and clinical relevance of clavulanate-induced antagonism of ticarcillin against specific bacterial strains.
  • To determine if clavulanate-induced beta-lactamase activity affects ticarcillin's efficacy.

Main Methods:

  • Utilized double disc tests and chequerboard microdilution assays to assess drug interactions.
  • Employed beta-lactamase-basal mutants and transconjugants to elucidate the role of enzyme induction.

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  • Tested against various bacterial species including Pseudomonas aeruginosa, Enterobacter cloacae, and Morganella morganii.

    • Main Results:

    • Confirmed that clavulanate-induced beta-lactamase can antagonize ticarcillin in inducible strains, an effect abolished in basal mutants.
    • Significant antagonism (elevated MIC of ticarcillin) was observed in some Enterobacter cloacae and Morganella morganii strains.
    • Clavulanate showed synergy with ticarcillin against Proteus vulgaris by inhibiting its Class I enzyme.
    • Induction-determined antagonism was not reduced by TEM-1 beta-lactamase in Enterobacter cloacae transconjugants.

    Conclusions:

    • Clinical use of ticarcillin/clavulanate requires confirmation that Enterobacter cloacae and Morganella morganii strains are not more sensitive to ticarcillin alone.
    • Beta-lactamase induction typically causes transient resistance and is unlikely to lead to significant antagonism.
    • Distinguished reversible induction from the selection of stable, derepressed mutants, which is a separate clinical concern.