Antibiotics & Antibiotic Resistance

Biography

Biography: Sheila Connelly

Abstract

Beta-lactamases, generally considered the “enemy”, are natural, bacterial-derived enzymes that degrade betalactam antibiotics, confer antibiotic resistance, and dramatically complicate the treatment of bacterial infections. Synthetic Biologics, Inc. has harnessed the potent antibiotic hydrolyzing power of this enzyme class to develop a prophylactic intervention intended to inactivate selected beta-lactam antibiotics in the GI tract to protect the gut microbiome and to prevent the emergence of antimicrobial resistance (AMR). SYN-004, ribaxamase, is intended for use with IV penicillins and cephalosporins. SYN-004, formulated for oral delivery into enteric-coated pellets to protect the enzyme from stomach acid, is released in the upper small intestine at pH>5.5. Animal and human studies demonstrated that ribaxamase degraded antibiotics in the upper GI tract protected the gut microbiome, and reduced AMR. Further examination of this prevention approach, in a phase 2b clinical study, demonstrated that ribaxamase significantly reduced Clostridium difficile infection in high-risk patients who were receiving ceftriaxone for treatment of a lower respiratory tract infection without compromising pulmonary infection control. A new ribaxamase formulation, called SYN-007, was engineered for release in the lower small intestine distal to the site of oral amoxicillin systemic absorption. SYN-007 protected the gut microbiome from damage caused by oral amoxicillin without affecting amoxicillin systemic absorption in dogs. Antibiotic inactivation represents a promising potential new treatment paradigm for the preservation of the gut microbiome and reduction of AMR. SYN-007 is intended to expand beta-lactamasemediated microbiome protection to oral as well as IV beta-lactam antibiotics.