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Relationship between the level of acquired resistance to gentamicin and synergism with amoxicillin in Enterococcus

Elisabeth Aslangul1, Raymond Ruimy, Françoise Chau

  • 1EA9933, Faculté de Médecine Xavier Bichat, Université Paris 7, USA.

Antimicrobial Agents and Chemotherapy
|September 29, 2005
PubMed

Insights

Intermediate gentamicin resistance in enterococci can still allow for synergistic effects with amoxicillin. This combination therapy remains beneficial in vivo, even with higher gentamicin concentrations, supporting current MIC clinical cutoff limits.

Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • Enterococci exhibit intrinsic low-level gentamicin resistance, but high-level resistance due to acquired enzymes negates amoxicillin synergism.
  • Understanding the impact of intermediate gentamicin resistance (64 < MIC < 500 µg/mL) on amoxicillin combination therapy is crucial for clinical application.

Purpose of the Study:

  • To investigate the in vitro and in vivo effects of intermediate gentamicin resistance on the synergistic activity of amoxicillin-gentamicin combination therapy in Enterococcus faecalis.

Main Methods:

  • In vitro selection of Enterococcus faecalis mutants with increasing gentamicin minimum inhibitory concentrations (MICs).
  • In vitro killing curves to assess synergistic activity of amoxicillin-gentamicin combinations.
  • In vivo rabbit model of aortic endocarditis to evaluate treatment efficacy.

Main Results:

  • In vitro synergism with amoxicillin required progressively higher gentamicin concentrations as gentamicin resistance increased.
  • Amoxicillin-gentamicin combination therapy demonstrated significant in vivo efficacy against intermediate gentamicin-resistant strains (G1, G2) but not high-level resistant strains (G3, 102).
  • A gentamicin MIC of 500 µg/mL was identified as a reliable cutoff for predicting in vivo benefit of the combination therapy.

Conclusions:

  • Intermediate levels of gentamicin resistance do not abolish the beneficial synergistic effect of amoxicillin-gentamicin combination therapy in vivo.
  • The established clinical MIC cutoff of 500 µg/mL for gentamicin effectively predicts the in vivo efficacy of this combination therapy.

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