The ongoing fight against deadly "superbugs" that have grown resistant to antibiotics is aimed at an elusive goal: finding a way to allow antibiotics to do their crucial work, while simultaneously preventing side-effects that damage our natural disease-fighting gut microbiome, whose "good bacteria" are vital to our health.
Thanks to SYN-004 (ribaxamase), derived from a naturally occurring enzyme, and a group of pigs that aided our research, we presented some promising new developments at Digestive Disease Week® (DDW) 2017, the world's largest gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Our research team at Synthetic Biologics has found that ribaxamase, which is designed to break down most broad-spectrum, beta-lactam antibiotics in the gut, can protect the microbiome in pigs and reduce the occurrence of potentially deadly Clostridium difficile infections in humans. By protecting the gut microbiome from the unintended deleterious effects of antibiotics, we also discovered that ribaxamase may mitigate the emergence of antibiotic-resistant bacteria, another encouraging finding.
For our study, we treated three groups of pigs with one of three antibiotics — IV ceftriaxone, oral amoxicillin or IV ertapenem — and another group of pigs with the combination of IV ceftriaxone and ribaxamase. After a week of treatment, we sequenced the pigs' fecal DNA to assess the effect of antibiotic treatment on the gut microbiome, the complex collection of microbes important for health. We also measured the presence of antibiotic resistance genes as a gauge for the presence of antibiotic-resistant bacteria.
Our team found that pigs receiving both ribaxamase and IV ceftriaxone preserved their native, pre-treatment gut microbiomes. We also saw that ribaxamase reduced emergence and spread of antibiotic resistance genes, genes conferring resistance to broad spectrum beta-lactam antibiotics, such as penicillins and cephalosporins, as well as non-beta-lactam antibiotics, such as macrolides and aminoglycosides.
With all three groups of pigs that received only antibiotics, we saw significant changes in their gut microbiomes. Additionally, within just four days of receiving antibiotic treatment, we saw the emergence of a wide array of antibiotic resistant genes suggesting the presence of bacteria resistance to beta-lactam antibiotics and non-beta-lactam antibiotics.
Some may worry that ribaxamase, while protecting the gut microbiome, might reduce the effectiveness of the antibiotic in fighting the original infection. That's not a concern — ribaxamase is designed to be released and stay in the gut, isolating its antibiotic-degradation activity to the targeted area.
One caveat — ribaxamase does not degrade all antibiotics, including carbapenems. But, the beta-lactam antibiotics that ribaxamase does inactivate, such as piperacillin and ceftriaxone, are the most commonly used broad spectrum IV antibiotics and these antibiotics wreak havoc on the gut microbiome.
Although we conducted this study in pigs, previous experience tells us that the results from pig models are often translatable to humans. Imagine a time when we will be less worried about the emergence of superbugs, while still practicing responsible use of antibiotics.
With these favorable results, our team is now testing whether a change in the ribaxamase delivery method can also protect the gut when used with oral beta-lactam antibiotics, such as amoxicillin.
The microbiome plays a significant role in maintaining our physical and mental well-being. Our goal is to reduce the risks associated with the use of highly effective, broad spectrum beta-lactam antibiotics to ensure protection of the gut microbiome and to mitigate emergence of antibiotic resistance.
Sheila Connelly, PhD, is vice president of research at Synthetic Biologics, Inc., a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients. Funding for this study was provided by Synthetic Biologics, a public company trading on the NYSE under the stock ticker SYN.
Dr. Connelly will present data from the study "An orally delivered beta-lactamase protects the gut microbiome from antibiotic-mediated damage and mitigates the propagation of antibiotic-resistance genes in a porcine dysbiosis model," abstract 332g, on Sunday, May 7, at 2:15 p.m. CT, at McCormick Place in Chicago. For more information about featured studies, as well as a schedule of availability for featured researchers, please visit www.ddw.org/press.
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