Impact of oral fidaxomicin administration on the intestinal microbiota and susceptibility to Clostridium difficile colonization in mice [PublishAheadOfPrint]

Clostridium difficile infection (CDI), a common cause of hospital-acquired infections, typically occurs after disruption of the normal gut microbiome by broad-spectrum antibiotics. Fidaxomicin is a narrow-spectrum antibiotic that demonstrates reduced impact on the normal gut microbiota and is approved for the treatment of CDI. To further explore the benefits of this property, we used a murine model to examine the effects of fidaxomicin versus vancomycin on gut microbiota and susceptibility to C. difficile colonization while tracking microbiota recovery over time.

Mice were exposed to fidaxomicin or vancomycin by oral gavage for 3 days, and subsequently challenged with C. difficile spores at predetermined time points up to 21 days post-antibiotic exposure. Fecal samples were subsequently collected for analysis. Twenty-four hours post-challenge, mice were euthanized and colon contents harvested. The microbiota was characterized using 16S rDNA gene sequencing.

All fidaxomicin exposed mice (except for one at Day 8) were resistant to C. difficile colonization. However, 9 of 15 vancomycin exposed mice were susceptible to C. difficile colonization until Day 12. All vancomycin exposed mice recovered colonization resistance by Day 16. Bacterial diversity was similar prior to antibiotic exposure in both arms and decreased substantially after exposure. A shift in taxonomic structure and composition occurred after both exposures; however, the shift was greater in vancomycin- than in fidaxomicin-exposed mice.

In summary, compared with vancomycin, fidaxomicin exposure had less impact on microbiota composition, promoted faster microbial recovery and had less impact on loss of C. difficile colonization resistance.

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