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Gentamicin improves the activities of daptomycin and vancomycin against Enterococcus faecalis in vitro and in an

Ulrika Furustrand Tafin1, Ivana Majic, Cyrine Zalila Belkhodja

  • 1Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.

Antimicrobial Agents and Chemotherapy
|August 3, 2011
PubMed

Insights

Daptomycin showed better activity than vancomycin against enterococcal implant infections. Combining daptomycin or vancomycin with gentamicin improved cure rates in an animal model, though eradication remains challenging.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Enterococcal implant-associated infections lack defined optimal treatment regimens.
  • Enterococcus faecalis is a common pathogen in these difficult-to-treat infections.
  • Evaluating antibiotic efficacy against adherent bacteria is crucial for treatment strategies.

Purpose of the Study:

  • To investigate the in vitro and in vivo activity of daptomycin, vancomycin, and gentamicin against Enterococcus faecalis.
  • To assess the efficacy of antibiotic combinations in a foreign-body infection model.
  • To determine optimal treatment strategies for enterococcal implant-associated infections.

Main Methods:

  • In vitro studies included time-kill assays and microcalorimetry.
  • A guinea pig foreign-body infection model with subcutaneously implanted cages was utilized.
  • Antibiotic treatment (daptomycin, vancomycin, gentamicin, and combinations) was administered for 4 days, starting 3 hours post-infection.

Main Results:

  • Daptomycin demonstrated greater activity than vancomycin against adherent E. faecalis in vitro.
  • Gentamicin, even at subinhibitory concentrations, enhanced the activity of daptomycin and vancomycin in vitro.
  • In the animal model, daptomycin achieved a 55% cure rate when combined with gentamicin, compared to 25% for daptomycin alone. Vancomycin with gentamicin achieved 33% versus 17% alone.

Conclusions:

  • Daptomycin is more effective than vancomycin against adherent E. faecalis, with synergistic improvement observed when combined with gentamicin.
  • The combination of daptomycin and gentamicin offers the highest cure rate (55%) in this early-stage implant infection model.
  • Eradicating E. faecalis from implants, even in the early stages, remains a significant clinical challenge, necessitating further research into treatment optimization.

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