Development of systemic bacteraemia after oral inoculation of vancomycin-resistant enterococci in mice

Bacteraemia caused by vancomycin-resistant enterococci (VRE) is an importan t 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 trea tment of mice with cyclophosphamide and a combination of metronidazole, kan amycin and vancomycin reduced normal intestinal flora and induced systemic VRE bacteraemia, Translocation of VRE and the normal intestinal flora to th e mesenteric lymph nodes, liver, spleen and blood, and mortality rate were dependent on treatment with cyclophosphamide and each of the three antimicr obial drugs. Among the different strains studied, C57BL/6 mice were the mos t susceptible to VRE, The virulence of vancomycin-resistant Enterococcus fa ecalis was greater than that of vancomycin-resistant Ent, faecium. On the d ay 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 b lood samples obtained from dead and dying mice, and VRE organisms outnumber ed E, coli in those samples by 100:1 or more. These results indicate that c hanges in normal intestinal flora by administration of antimicrobial drugs and severity of neutropenia induced by cyclophosphamide are important facto rs that contribute to the development of systemic VRE bacteraemia, E, coli may be intimately associated with the establishment of VRE translocation.