title: Development of systemic bacteraemia after oral inoculation of vancomycin-resistant enterococci in mice.
abstract: Bacteraemia caused by vancomycin-resistant enterococci (VRE) is an important clinical problem because there are only a few potent antimicrobial agents against such bacteria. Therefore, understanding the pathogenic mechanisms of VRE bacteraemia is important for prophylaxis. This study shows that treatment of mice with cyclophosphamide and a combination of metronidazole, kanamycin and vancomycin reduced normal intestinal flora and induced systemic VRE bacteraemia. Translocation of VRE and the normal intestinal flora to the mesenteric lymph nodes, liver, spleen and blood, and mortality rate were dependent on treatment with cyclophosphamide and each of the three antimicrobial drugs. Among the different strains studied, C57BL/6 mice were the most susceptible to VRE. The virulence of vancomycin-resistant Enterococcus faecalis was greater than that of vancomycin-resistant Ent. faecium. On the day after inoculation of VRE, Escherichia coli was also detected in many VRE-positive specimens including blood, liver and the mesenteric lymph nodes. Moreover, both VRE and E. coli were detected simultaneously in almost all blood samples obtained from dead and dying mice, and VRE organisms outnumbered E. coli in those samples by 100:1 or more. These results indicate that changes in normal intestinal flora by administration of antimicrobial drugs and severity of neutropenia induced by cyclophosphamide are important factors that contribute to the development of systemic VRE bacteraemia. E. coli may be intimately associated with the establishment of VRE translocation.
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujikawa
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Intetsu
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.affiliation: Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D019072:Antibiotic Prophylaxis; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D018988:Bacterial Translocation / Q000187:drug effects; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016983:Enterococcus / Q000187:drug effects* / Q000472:pathogenicity; D004926:Escherichia coli / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007422:Intestines / Q000382:microbiology; D007612:Kanamycin / Q000009:adverse effects / Q000627:therapeutic use; D008795:Metronidazole / Q000009:adverse effects / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D016513:Mice, SCID; D009503:Neutropenia / Q000139:chemically induced; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use; D020713:Vancomycin Resistance; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D008795:Metronidazole; D007612:Kanamycin; D014640:Vancomycin; D003520:Cyclophosphamide