title: The optimal aminoglycoside and its dosage for the treatment of severe Enterococcus faecalis infection. An experimental study in the rabbit endocarditis model.
abstract: Aminoglycosides are recommended for the treatment of Enterococcus faecalis infections, especially in severe and bacteremic infection. However, the optimal aminoglycoside or the optimal dosage remains uncertain. This study aimed to compare the activity of four aminoglycosides against E. faecalis (gentamicin, netilmicin, tobramycin, and amikacin) and two dosages of gentamicin. One clinical strain of E. faecalis was used to induce aortic endocarditis in the study rabbits. Each aminoglycoside was infused daily over 3 days with a computer-regulated flow simulating human pharmacokinetics of 15 mg/kg/day for amikacin, 6 mg/kg/day for netilmicin, and 3 mg/kg/day for gentamicin and tobramycin. Additionally, two dosages of gentamicin (simulating 3 or 6 mg/kg/day) were compared over 1 or 3 days of treatment. The in vivo efficacy was assessed according to the bacterial count in vegetations, in comparison with a control group. Of the four aminoglycosides tested, only gentamicin and netilmicin showed significant antibacterial efficacy after 3 days of treatment. After only 1 day of treatment, the high dosage of gentamicin (6 mg/kg/day) was more effective than the standard dosage (3 mg/kg/day). Among the tested aminoglycosides, gentamicin showed the best efficacy, with the best results after 24 h of treatment for the highest dosage.
authors.affiliation: Faculté de Médecine, Laboratoire EA3826, Université de Nantes, 1 rue Gaston Veil, Nantes 44035, France.
authors.forename: L
authors.initials: L
authors.lastname: Dubé
authors.forename: J
authors.initials: J
authors.lastname: Caillon
authors.forename: C
authors.initials: C
authors.lastname: Jacqueline
authors.forename: D
authors.initials: D
authors.lastname: Bugnon
authors.forename: G
authors.initials: G
authors.lastname: Potel
authors.forename: N
authors.initials: N
authors.lastname: Asseray
mesh_terms: D000583:Amikacin / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D058491:Bacterial Load; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000187:drug effects / Q000472:pathogenicity; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000494:pharmacology*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D009428:Netilmicin / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009428:Netilmicin; D000583:Amikacin; D014031:Tobramycin