title: In vivo activity of the combination of daptomycin and fosfomycin compared with daptomycin alone against a strain of Enterococcus faecalis with high-level gentamicin resistance in the rat endocarditis model.
abstract: The in vivo activity of the combination of daptomycin and fosfomycin against a beta-lactamase-producing, highly gentamicin-resistant strain of Enterococcus faecalis in a relapse model of rat endocarditis was studied. Minimum inhibitory concentrations (MICs) (micrograms per milliliter) for these agents against this strain were 4 (daptomycin) and 16 (fosfomycin). Time-kill studies demonstrated synergistic bactericidal activity when daptomycin (0.5 micrograms/ml) and fosfomycin (32 micrograms/ml) were combined. There was no significant difference between the number of valves sterilized by daptomycin alone [six (35%) of 17 valves sterilized] and daptomycin+fosfomycin [ten (59%) of 17 valves sterilized] p = 0.3. These results suggest that the in vitro bactericidal synergism demonstrable between these two agents against strains of enterococci will not necessarily translate into greater therapeutic efficacy in clinical infections.
authors.affiliation: Department of Medicine, New England Deaconess Hospital, Boston, MA 02215.
authors.forename: L B
authors.initials: LB
authors.lastname: Rice
authors.forename: C T
authors.initials: CT
authors.lastname: Eliopoulos
authors.forename: J D
authors.initials: JD
authors.lastname: Yao
authors.forename: G M
authors.initials: GM
authors.lastname: Eliopoulos
authors.forename: R C
authors.initials: RC
authors.lastname: Moellering
mesh_terms: D000818:Animals; D017576:Daptomycin; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology / Q000627:therapeutic use; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D013293:Enterococcus faecalis / Q000187:drug effects*; D005578:Fosfomycin / Q000494:pharmacology / Q000627:therapeutic use*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D008297:Male; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010455:Peptides; D005578:Fosfomycin; D017576:Daptomycin