Perturbation of the intestinal microbiota, primarily by antibiotics, is a risk factor for Clostridium difficile infection (CDI).
Restoration of a variable intestinal microbiota protects against recurrence of CDI.
RBX2660 is a microbiota-based drug under study for the prevention of recurrent CDI.
We evaluated the impact of RBX2660 treatment on the intestinal microbiota of patients enrolled in the PUNCH CD 2 trial, a multicenter, randomized, double-blinded, placebo controlled phase 2b study.
Patients in the 3-arm PUNCH CD 2 trial were randomized 1:1:1 to receive either: 2 doses of RBX2660 (Group A); 2 doses of placebo (Group B); or 1 dose of RBX2660 and 1 dose of placebo (Group C). Success was defined as the absence of Clostridium difficile-associated diarrhea at 8 weeks following completion of the last treatment.
Failure was defined as recurrence of CDI symptoms; a positive stool test; a need for CDI retreatment; and no other cause for CDI symptoms within 8 weeks.
Longitudinal 16s rRNA analysis using the Illumina MiSeq platform was performed on a total of 120 stool samples from patients in the 3 arms of the study (Group A: n=23; Group B: n=22; Group C: n= 22) at baseline, 7 days and 30 days after the second blinded dose.
The variable region V4 was targeted to identify the operational taxonomic units (OTUs) in each sample.
At baseline, the microbiota profiles were similar across all samples.
OTU analysis demonstrated higher diversity between baseline and follow-up time points for all patients who responded successfully to their assigned treatment.
The higher diversity at follow-up points was also true for placebo responders (12 patients in Group B who received two doses of placebo and did not experience recurrent CDI symptoms prior to 8-week follow-up).
Specifically, successful Group A patients had an increase in Akkermansia and Bacteroides from baseline; successful Group B and C patients had a decreased abundance of Enterobacter (Figures 1-3).
Of the three groups of patients, those in Group A (two doses of active treatment) showed the greatest increase in bacterial diversity (number of OTUs) and abundance of taxa between baseline and all follow-up points (Figure 4).
In this randomized, placebo-controlled study of RBX2660 for recurrent CDI, 16s rRNA analysis found that patients who succeeded with their assigned therapy had a more diverse intestinal microbiota at 7 and 30 days compared with baseline.