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Comparative activity of imipenem (N-formimidoyl thienamycin) on enterococci and its interactions with aminoglycosides

Insights

Imipenem effectively inhibits Streptococcus faecalis and Streptococcus faecium, showing strong bactericidal activity. Its combination with streptomycin and sissomicin demonstrated synergistic effects against these bacteria.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Enterococcus species, including Streptococcus faecalis and Streptococcus faecium, are significant causes of nosocomial infections.
  • Antimicrobial resistance in enterococci necessitates the evaluation of existing and novel therapeutic agents.
  • Understanding the synergistic or antagonistic interactions between antibiotics is crucial for optimizing treatment strategies.

Purpose of the Study:

  • To determine the in vitro activity of imipenem, ampicillin, and vancomycin against clinical isolates of Streptococcus faecalis and Streptococcus faecium.
  • To evaluate the in vitro interactions of imipenem, ampicillin, and vancomycin when combined with aminoglycosides (streptomycin, amikacin, sissomicin).

Main Methods:

  • Determination of Minimum Inhibitory Concentrations (MIC50 and MIC90) for imipenem, ampicillin, and vancomycin against 27 Streptococcus faecalis and 5 Streptococcus faecium strains.
  • Evaluation of bactericidal activity using Minimum Bactericidal Concentrations (MBC50 and MBC90).
  • Assessment of drug interactions (synergy, addition, indifference, antagonism) using checkerboard titration or similar methods for antibiotic combinations.

Main Results:

  • Imipenem exhibited potent inhibitory activity against Streptococcus faecalis (MIC50/MIC90: 0.5/2 mg/l) and good bactericidal activity (MBC50/MBC90: 1/4 mg/l).
  • Streptococcus faecium strains showed reduced susceptibility to imipenem (MIC50/MIC90: 2/16 mg/l) with less potent bactericidal activity (MBC50/MBC90: 4/16 mg/l).
  • The most favorable interactions for imipenem were with streptomycin (72.2% synergy/addition) and sissomicin (53.2%), while combinations with amikacin were least favorable.

Conclusions:

  • Imipenem demonstrates significant in vitro activity against Streptococcus faecalis and Streptococcus faecium, with notable bactericidal effects.
  • Combinations of imipenem with streptomycin or sissomicin show promising synergistic or additive effects, suggesting potential clinical utility.
  • Further investigation into imipenem-aminoglycoside combinations is warranted for treating enterococcal infections.

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