Extended Data Fig. 5: Rifaximin drives daptomycin resistance in VREfm colonized mice.

a. Timeline of the mouse experiment. VREfm-colonized mice (n = 5 independent mice for vehicle, n = 10 independent mice for rifampicin, n = 10 independent mice for rifaximin, n = 10 independent mice for daptomycin) received a human-equivalent dose of vehicle, rifampicin, or rifaximin (twice per day for rifaximin) for 7 days by oral gavage or subcutaneous injection with daptomycin for 7 days. CRO=ceftriaxone; DAP=daptomycin; RIFAX=rifaximin; RIF=rifampicin. Figure to scale. b. The colony forming units (CFU) for the duration of the mouse experiment. Each point represents the average VREfm CFU/g of faeces and error bars represent standard error of the mean. n = 5 independent mice for vehicle and n = 10 independent mice for DAP, RIF, and RIFAX. The x-axis is day of collection and y-axis is the CFU/g faeces of VREfm. c. Percentage of mice with rifampicin-resistant VREfm strains for each treatment group. d. Percentage of VREfm from each mouse (n = 50 colonies from each individual mouse) that were resistant to rifampicin after 7 days of antibiotic treatment. Points represent the percentage of rifampicin-resistant VREfm from each individual mouse. Percentage was calculated from rifampicin MIC values (either resistant or susceptible) from the 50 VREfm colonies isolated from each mouse. For all box plots, the lower and upper hinges depict the 25th and 75th percentiles. The upper and lower whiskers extend from the hinge to the largest and smallest values at most 1.5 × IQR from the hinge. The centre line in the box shows the median. Data in c and d were analysed using an unpaired t-test (two-sided) (vehicle versus rifampicin or vehicle versus rifaximin and rifampicin versus daptomycin or rifaximin versus daptomycin). Exact P values are provided when the P value is above P < 0.0001. The y-axes represent the percentage of rifampicin-resistant VREfm isolates.

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