Novel Antibacterial Demonstrates Superiority to Vancomycin for C difficile Infection

AUGUST 24, 2018
Brandon May
Ridinilazole, a novel antibacterial drug, was associated with a lower disruption to the microbiota in patients with Clostridium difficile infection, according to a study led by Cheleste M. Thorpe, MD, of the Tufts Medical Center. The investigators believe these findings suggest that ridinilazole may be more effective than vancomycin in reducing recurrence of C difficile infection.

“This novel finding of this study is the limited disruption of intestinal microbiota following ridinilazole treatment, both in terms of biomass (how many are there) and composition (which taxonomic groups are represented),” the investigators wrote in their PLoS One study. “Both are likely important in preventing C difficile colonization, disease, and recurrence, by preserving sufficient density of the correct type(s) of species to create an environment not conducive to C difficile expansion.”

For the study, a total of 100 patients with C difficile infection were randomized (1:1) to a 10-day regimen consisting of either vancomycin (n = 50) or ridinilazole (n = 50). In the primary analysis, only 22 patients were enrolled in each group. Study participants were compared with an age- and sex-matched control comprised of healthy volunteers (n = 14).

For the purposes of the study, investigators compared ridinilazole and vancomycin in terms of their effects on fecal microbiota both during and following therapy in patients who previously experienced benefit with ridinilazole in a phase 2 trial. A quantitative polymerase chain reaction (qPCR) analysis was performed to assess for microbiota changes, and high-throughput sequencing was performed on stool samples at baseline (day 1), day 5, end of treatment (EOT) on day 10, day 25, end of study (EOS) on day 40, and at recurrence of C difficile infection.

At EOT, treatment with vancomycin was associated with substantial losses in Bacteroides, C coccoides, C leptum, and Prevotella. Enterobacteriaceae increased in patients treated with vancomycin, which was demonstrated following EOT. Conversely, participants randomized to ridinilazole experienced a slight reduction in levels of C leptum at the same time; however, these levels recovered by 25 days of treatment.

Both antibiotic treatments demonstrated a reduction in alpha diversity at EOT; however, ridinilazole was associated with a greater decrease compared with vancomycin (P<.0001). Additionally, the microbiota composition observed at baseline returned back to baseline levels sooner with ridinilazole vs vancomycin treatment. Vancomycin was also associated with a significant decrease in Firmicutes, Bacteroidetes, and Actinobacteria groups. In addition, patients treated with vancomycin also experienced an increase in the abundance of Proteobacteria.

The main limitation of the analysis includes its relatively small sample size, which reduces the ability to make definitive inferences regarding the generalizable benefit of ridinilazole in the C difficile infection population.

“Ridinilazole is a promising, effective C difficile infection antimicrobial with minimal effects on bystander indigenous colonic flora,” the researchers summarized in a closing statement. “Its microbiota-preserving narrow-spectrum activity is likely responsible for the observed decreased recurrence rate compared to vancomycin treatment.”

The study, “Enhanced preservation of the human intestinal microbiota by ridinilazole, a novel Clostridium difficile-targeting antibacterial, compared to vancomycin,” was published in PloS One.

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