Probiotics and intestinal colonization by vancomycin-resistant enterococci in mice and humans

Abstract

We investigated the impact of probiotics on the intestinal carriage of vancomycin-resistant enterococci (VRE). Administration of Lactobacillus rhamnosus Lcr35 but not Escherichia coli Nissle reduced, although not significantly, the density of VRE colonization in a murine model. No effect of Lcr35 was observed in a double-blind placebo randomized study, involving nine patients.

Trial registration: ClinicalTrials.gov NCT00437580.

Figures

FIG. 1.

Persistence and density of vancomycin-resistant Enterococcus faecium (VRE) intestinal colonization in mice. Mice received either vancomycin (▪) or saline (⧫) 7 days before and after VRE gastric inoculation (from D0 to D14). Stool VRE levels (CFU/g of feces) were quantified every 2 or 3 days from D8 until D80. In the control group, the number of VRE CFU was under the limit of detection (1.4 × 102 CFU/g) from D41.

FIG. 2.

Effect of an 8-day course of administration of either Lactobacillus rhamnosus Lcr35 or Escherichia coli Nissle on intestinal carriage of vancomycin-resistant Enterococcus faecium (VRE). All mice received vancomycin (250 μg/ml) in drinking water for 14 days, and VRE gastric inoculation was performed on D7. On D14, vancomycin was stopped and mice received once daily either probiotic (•, Lcr35, 108 CFU; ○, E. coli Nissle, 109 CFU) or saline (▴), for 8 days. Stool VRE levels were quantified over a period of 4 weeks.

FIG. 3.

TTGE analysis of 16S rRNA (V6 to V8) amplification products from feces samples collected over time (40 days) of mice receiving vancomycin (D0 to D14) followed (test group) or not (control group) by daily administration of Lcr35 (D15 to D21). Representative example of TTGE community profile (A) and its phylogenetic tree constructed using Dice's coefficient (B) of an animal from the test group. The periods of vancomycin and probiotic administration are indicated by horizontal double arrows, and VRE gastric inoculation is indicated by a vertical arrow. MW, molecular weight markers.

FIG. 4.

Outcome of VRE colonization in patients receiving Lcr35 (solid arrow, n = 6) versus placebo (dashed arrow, n = 2) for a 5-week period (W1 to W5). VRE was detected in patient stools from W1 to W11; black bars, positive VRE cultures; gray bars, negative VRE cultures. Nine VRE-positive patients were recruited. One patient died 2 days after inclusion and was excluded from the analysis. Of the eight remaining patients, six received Lcr35 and two received placebos. Patients 1 and 2 completed the treatment with placebo but stopped the study after W7. Patient 5 stopped the treatment with Lcr35 after 3 weeks. The Charlson index of comorbidity was 3 to 4 for two patients and higher than 5 for six of them.