Optimization of vancomycin resistant Enterococcus infection model in mice

Abstract

Objective To optimize the intestinal colonization model of vancomycin resistant Enterococcus (VRE) in mouse model, and evaluate the effect of antibiotic pretreatment and different infection dosages on the intestinal VRE colonization. Methods C57/6J mice were randomly divided into 3 pretreatment groups, which were mixed antibiotic pretreatment group, ampicillin and clindamycin pretreatment group and vancomycin pretreatment group. In mixed pretreatment antibiotic group, the mice were given mix antibiotic solution (kanamycin, gentamicin, colistin, metronidazole, vancomycin) on day 7 before infection; on day 2 before infection, vancomycin solution was given instead of the mixed antibiotic solution, and intraperitoneal injection of clindamycin was given on day 1 before infection. In ampicillin and clindamycin pretreatment group, the mice were given ampicillin solution on day 7 before infection, and intraperitoneal injection of clindamycin was given 1 day before infection. In vancomycin pretreatment group, vancomycin solution was given on day 7 before infection. On day 0, three groups of mice were infected with VRE. On day 3 after infection, vancomycin solution and ampicillin solution were changed to normal drinking water. The collected fecal live bacteria were counted within 2 weeks after infection, and changes of VRE colonization were observed. Results Three antibiotic-pretreated mouse models infected with VRE were successfully established, and VRE were successfully colonized on day 1 after infection. Within 1–9 days after infection, the VRE contents in feces of the three models was 105–108cfu/mg. Nine days after infection, the colonization of VRE in the three mouse groups showed downward trends, and the content of VRE in the mouse feces decreased to 103–105cfu/mg on the 15th day. And, we observed that two mice died in the ampicillin group on day 10 after infection. There was no significant difference in VRE colonization between high dosage group and low dosage group during the acute infection period in vancomycin pretreated mice. Conclusion The stability and simplicity of vancomycin-pretreated mouse model was superior to those of the other two antibiotic-pretreated mouse models. By the end of the experiment, VRE could successfully colonize in the intestinal tract of the mice for more than 15 days in vancomycin pretreatment group, and the VRE intestinal colonization model could be established steadily at the infection dosages ranging from 105 cfu to 107 cfu per mouse.