title: Comparative efficacies of daptomycin, vancomycin, and linezolid in experimental enterococcal peritonitis.
abstract: Enterococci have become increasingly important pathogens for nosocomial infection (e.g. bacteremia, intra-abdominal infection, endocarditis, etc.), related to their intrinsic resistance to many antibiotics. Although the in vitro susceptibility of daptomycin (DAP) against Enterococci is well established, the Food and Drug Administration has only approved its use for complicated skin and skin structure infections induced by Enterococcus faecalis. In this study we evaluated the potential therapeutic application of DAP in a murine model of enterococcal experimental peritonitis. Mice were injected intraperitoneally with 4 × 1010colony-forming units of Enterococcus faecium. DAP alone, DAP combined with ampicillin, vancomycin, or linezolid were administered 2 h after enterococcal inoculation and examined the survival, viable bacteria counts, the level of KC/CXCL1 in the peritoneal fluid. The viable bacteria counts in the peritoneal fluid of the DAP- or DAP plus ampicillin-treated groups were decreased significantly compared to those of the vancomycin- and linezolid-treated groups (P < 0.05) at 6 and 12 h after the inoculation of Enterococcus. The level of neutrophil chemoattractants KC in the peritoneal fluid at 12 h after enterococcal inoculation was significantly decreased in the DAP plus ampicillin-treated group (P < 0.05). In addition DAP showed the inhibitory effect of enterococcal biofilm formation dose-dependently by a microtiter biofilm assay. These results indicate that DAP, particularly with β-lactams, is a possible alternative agent to treat severe enterococcal infection such as peritonitis.
authors.affiliation: Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Molecular and Internal Medicine, Hiroshima University, Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kajihara
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan. Electronic address: shigekinak@nih.go.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Iwanaga
authors.affiliation: Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Oshima
authors.affiliation: Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Department of Infectious Diseases, Unit of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Taiga
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Infectious Diseases, Unit of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Izumikawa
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Molecular and Internal Medicine, Hiroshima University, Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Molecular and Internal Medicine, Hiroshima University, Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.affiliation: Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.affiliation: Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016983:Enterococcus; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D000069349:Linezolid / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000188:drug therapy*; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin
keywords: Biofilm; Combination with β-lactams; Daptomycin; Enterococcal peritonitis