Abstract

Multi-drug-resistant Enterobacteriales expressing a wide array of β-lactamases are emerging as a global health threat in both hospitals and communities. Although several intravenous drugs have recently been approved to address this need, there are no oral Gram-negative agents that are both safe and broadly effective against such pathogens. The lack of an effective oral agent is of concern for common infections which could otherwise be treated in the community but, due to antibiotic resistance, require hospitalization to allow for intravenous therapy. ETX1317 is a novel, broad spectrum, serine β-lactamase inhibitor of the diazabicyclooctane class that restores the antibacterial activity of multiple β-lactams against multiple species of multi-drug-resistant Enterobacteriales, including carbapenem-resistant strains. A combination of its oral prodrug, ETX0282, and the oral prodrug of a third-generation cephalosporin, cefpodoxime proxetil, is currently in clinical development. This report describes the biochemical and microbiological properties of ETX1317, which is more potent and demonstrates a greater breadth of inhibition than avibactam, the parenteral prototype of this class of β-lactamase inhibitors.

Highlights

  • Multi-drug-resistant Enterobacteriales expressing a wide array of β-lactamases are emerging as a global health threat in both hospitals and communities

  • A number of intravenous drugs have been approved in recent years to address this need (AVYCAZ, Zerbaxa, Vabomere, Zemdri, Zerava, Recarbrio, Fetroja4−9), there are no oral Gram-negative agents that are both safe and broadly effective against drug-resistant urinary tract infections (UTIs) pathogens

  • ETX1317, a novel member of the diazabicyclooctane class of β-lactamase inhibitors, is the active moiety of the orally available prodrug ETX0282,16 which is currently in clinical development in combination with the oral prodrug of a thirdgeneration cephalosporin, cefpodoxime proxetil, for the treatment of infections caused by drug resistant Enterobacteriales

Read more

Summary

Introduction

Multi-drug-resistant Enterobacteriales expressing a wide array of β-lactamases are emerging as a global health threat in both hospitals and communities. The vast majority (∼75%) of these are due to Escherichia coli, but Klebsiella, Enterobacter, Citrobacter, and Proteus spp. are important uropathogens.[2,3] a number of intravenous drugs have been approved in recent years to address this need (AVYCAZ, Zerbaxa, Vabomere, Zemdri, Zerava, Recarbrio, Fetroja4−9), there are no oral Gram-negative agents that are both safe and broadly effective against drug-resistant UTI pathogens. ETX1317, a novel member of the diazabicyclooctane class of β-lactamase inhibitors, is the active moiety of the orally available prodrug ETX0282,16 which is currently in clinical development in combination with the oral prodrug of a thirdgeneration cephalosporin, cefpodoxime proxetil, for the treatment of infections caused by drug resistant Enterobacteriales (https://clinicaltrials.gov/ct2/show/ NCT03491748).

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call