The study enrolled 412 patients who were at least 50 years of age (mean age 70 years). Two-thirds of the patients were male, one-third had received macrolides, and one-third were receiving drugs to relieve stomach acidity. The intention-to-treat population who were “enriched for higher risk for CDI”, according to Dr. Kokai-Kun, were hospitalized for ≥5 days of intravenous ceftriaxone for treatment of lower respiratory tract infections. Half the patients were randomized to oral ribaxamase 150 mg, 4 times a day during the period of intravenous ceftriaxone treatment, and for another 72 hours. The other group received placebo along with ceftriaxone for the same times. Fecal samples were collected at randomization, at the end of the treatment period, and the end of the 6-week follow-up to determine the fecal microbiome by 16s ribosomal RNA sequencing.
The primary endpoint was prevention of CDI. The secondary endpoint was prevention of non-C- difficile
antibiotic-associated diarrhea. Exploratory endpoints evaluated the ability of the treatment regimen to curb the disruption of the gut microbiome.
In the placebo group, alpha and beta diversity analyses showed that the gut microbiome was significantly changed, while no appreciable change was evident in the ribaxamase group. The primary endpoint was met, with the ribaxamase group displaying a 71.4% relative risk reduction concerning CDI (P
= .045). There was a statistically significant 44% relative risk reduction in new colonization by vancomycin-resistant enterococci at 72 hours (P
= .0001) and 4 weeks (P
= .0002). New C. difficile
colonization was also reduced, but not significantly, in the ribaxamase group at 72 hours (P
= .059) and 4 weeks (P
Respiratory infection was cleared in nearly all (~99%) cases, indicating that the activity of ceftriaxone was not lessened by the presence of ribaxamase. Less diarrhea was evident in the ribaxamase group, but the change compared to the placebo group was not significant (P
“These data support that ribaxamase can maintain the balance of the gut microbiome and thereby prevent opportunistic infections like CDI during intravenous beta-lactam treatment,” said Dr. Kokai-Kun.
John Kokai-Kun, PhD; Synthetic Biologics, Inc.: Employee, Salary
Kokai-Kun J, Roberts T, Coughlin O, Whalen H, Le C, Da Costa C, Sliman J. SYN-004 (ribaxamase) prevents New Onset Clostridium difficile
Infection by Protecting the Integrity Gut Microbiome in a Phase 2b Study
Brian Hoyle, PhD, is a medical and science writer and editor from Halifax, Nova Scotia, Canada. He has been a full-time freelance writer/editor for over 15 years. Prior to that, he was a research microbiologist and lab manager of a provincial government water testing lab. He can be reached at firstname.lastname@example.org.
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