title: Gentamicin improves the activities of daptomycin and vancomycin against Enterococcus faecalis in vitro and in an experimental foreign-body infection model.
abstract: For enterococcal implant-associated infections, the optimal treatment regimen has not been defined. We investigated the activity of daptomycin, vancomycin, and gentamicin (and their combinations) against Enterococcus faecalis in vitro and in a foreign-body infection model. Antimicrobial activity was investigated by time-kill and growth-related heat production studies (microcalorimetry) as well as with a guinea pig model using subcutaneously implanted cages. Infection was established by percutaneous injection of E. faecalis in the cage. Antibiotic treatment for 4 days was started 3 h after infection. Cages were removed 5 days after end of treatment to determine the cure rate. The MIC, the minimal bactericidal concentration (MBC) in the logarithmic phase, and the MBC in the stationary phase were 1.25, 5, and >20 μg/ml for daptomycin, 1, >64, and >64 μg/ml for vancomycin, and 16, 32, and 4 μg/ml for gentamicin, respectively. In vitro, gentamicin at subinhibitory concentrations improved the activity against E. faecalis when combined with daptomycin or vancomycin in the logarithmic and stationary phases. In the animal model, daptomycin cured 25%, vancomycin 17%, and gentamicin 50% of infected cages. In combination with gentamicin, the cure rate for daptomycin increased to 55% and that of vancomycin increased to 33%. In conclusion, daptomycin was more active than vancomycin against adherent E. faecalis, and its activity was further improved by the addition of gentamicin. Despite a short duration of infection (3 h), the cure rates did not exceed 55%, highlighting the difficulty of eradicating E. faecalis from implants already in the early stage of implant-associated infection.
authors.affiliation: Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Furustrand Tafin
authors.forename: Ivana
authors.initials: I
authors.lastname: Majic
authors.forename: Cyrine
authors.initials: C
authors.lastname: Zalila Belkhodja
authors.forename: Bertrand
authors.initials: B
authors.lastname: Betrisey
authors.forename: Stéphane
authors.initials: S
authors.lastname: Corvec
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.forename: Andrej
authors.initials: A
authors.lastname: Trampuz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017576:Daptomycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D013293:Enterococcus faecalis / Q000187:drug effects*; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006168:Guinea Pigs; D008297:Male; D008826:Microbial Sensitivity Tests; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014640:Vancomycin; D017576:Daptomycin