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Development of systemic bacteraemia after oral inoculation of vancomycin-resistant enterococci in mice
Shuichi Miyazaki1, Toshihiko Fujikawa1, Intetsu Kobayashi1
1Department of Microbiology, Toho University School of Medicine, Tokyo, Japan.
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.
Insights
Vancomycin-resistant enterococci (VRE) bloodstream infections are a major concern. Antimicrobial drugs and chemotherapy-induced neutropenia disrupt gut flora, facilitating VRE translocation and systemic infection.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Vancomycin-resistant enterococci (VRE) bloodstream infections pose a significant clinical challenge due to limited treatment options.
- Understanding the pathogenesis of VRE bacteraemia is crucial for developing effective prophylactic strategies.
Purpose of the Study:
- To investigate the mechanisms underlying the development of systemic vancomycin-resistant enterococci bacteraemia in a murine model.
- To identify factors contributing to VRE translocation and mortality.
Main Methods:
- Mice were treated with cyclophosphamide and a combination of metronidazole, kanamycin, and vancomycin to induce neutropenia and alter intestinal flora.
- VRE translocation to mesenteric lymph nodes, liver, spleen, and blood was assessed.
- Mortality rates and the presence of Escherichia coli were monitored.
Main Results:
- Cyclophosphamide and antimicrobial drug treatment led to reduced normal intestinal flora and induced systemic VRE bacteraemia.
- VRE translocation and mortality were dependent on cyclophosphamide and specific antimicrobial drugs.
- Vancomycin-resistant Enterococcus faecalis exhibited greater virulence than vancomycin-resistant Enterococcus faecium in C57BL/6 mice.
- Escherichia coli was frequently detected alongside VRE, particularly in blood samples from deceased mice, suggesting a potential role in VRE translocation.
Conclusions:
- Disruption of normal intestinal flora by antimicrobial agents and cyclophosphamide-induced neutropenia are key factors in systemic VRE bacteraemia development.
- Escherichia coli may play a significant role in the translocation and establishment of VRE infections.