Coadministration of Ribaxamase with IV Beta-lactam Antibiotics May Reduce Emergence of Antibiotic Resistance
Coadministration of ribaxamase (SYN-004) in patients receiving IV beta-lactam antibiotics (eg, ceftriaxone) helps protect the integrity of the gut microbiome, thereby helping to limit the emergence of antibiotic-resistant microorganisms induced by these antibiotics, according to a presentation given by US researchers at ID Week 2018. The researchers noted that when beta-lactam antibiotics are administered intravenously, a significant portion of each dose can be excreted through the bile into the intestine, where this excess antibiotic can disrupt the balance of the gut microbiome and lead to the emergence of antimicrobial resistance (AMR).
Ribaxamase is an orally administered beta-lactamase designed to be given with IV beta-lactam antibiotics to degrade excess antibiotics excreted into the upper gastrointestinal tract before they can disrupt the gut microbiome and resistome. A phase 2b clinical study investigating the coadministration of ribaxamase with the IV antibiotic ceftriaxone revealed the following:
- Ribaxamase administration was associated with a significant reduction in Clostridium difficile infection.
- Genomic sequencing of patients’ fecal samples showed that ribaxamase protected the integrity of the gut microbiome, including preventing enterococcal mono-domination (defined as >30% of the microbiome being from one genus), and identified over 1300 AMR genes in the gut resistome.
- Analysis of the gut resistome identified a family of beta-lactamases and vancomycin resistance genes, which were significantly increased in placebo-treated versus ribaxamase-treated patients from pre-to post-antibiotics.
Kokai-Kun J, Le C, Trout K, et al. SYN-004 (ribaxamase) protects the gut microbiome of patients treated with ceftriaxone from disruption and reduces the emergence of antimicrobial resistance. Presented at: 2018 ID Week; October 3-7, 2018; San Francisco, California. Abstract 1337.