1072. In Vitro Antibacterial Susceptibility Testing of Sulopenem Against Category A and B Bio-threat Bacterial Pathogens

Abstract

Background Sulopenem is a thiopenem β-lactam antibiotic being developed for the treatment of infections caused by multi-drug resistant bacteria. Sulopenem possesses potent activity against species of the Enterobacterales that encode ESBLs or AmpC-type β-lactamases that confer resistance to third generation cephalosporins. It has also demonstrated good in vitro microbiological activity against a range of bacterial pathogens including penicillin resistant S. pneumoniae, β-lactamase-producing H. influenzae and M. catarrhalis. Sulopenem is available as intravenous and oral pro-drug formulations, and its activity aligns with the most urgent drug-resistant antimicrobial threats defined by the CDC. Methods Bacterial inoculums were prepared by suspending colonies into cation adjusted Mueller Hinton broth (CAMHB) from 18-24 h (B. anthracis, B. pseudomallei and B. mallei plates incubated at 35ºC); or 36-48 h (F. tularensis and Y. pestis plates incubated at 35ºC and 28ºC, respectively). Sheep blood agar plates were used for B. anthracis and Y. pestis. Chocolate agar plates were used for F. tularensis, B. pseudomallei and B. mallei. Suspended cultures were diluted with CAMHB to achieve a turbidity equivalent to a 0.5 McFarland standard. MICs were determined by the microdilution method in 96-well microplates according to CLSI guidelines (Clinical and Laboratory Standards Institute, 2020). Antibiotic ranges used for sulopenem were 0.03 - 64 μg/mL and 0.004 - 8 μg/mL for the diversity strains of B. anthracis, F. tularensis, Y. pesis, B. mallei, and B. pseudomallei, based on a final well volume of 100 μl after inoculation. Results A summary of sulopenem MIC90 results versus bio-threat bacterial pathogens in presented in the table. Criteria for down selection into mice was met for all pathogens except F. tularensis. Sulopenem MIC90 Summary for Down Selection Criteria Conclusion Sulopenem is active in vitro against a number of bio-threat pathogens at concentrations likely to be achieved after oral dosing in humans and meets criteria to be tested in the murine model of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei. Disclosures Michael Dunne, MD, Iterum Therapeutics (Board Member, Consultant, Shareholder) Steven I. Aronin, MD, Iterum Therapeutics (Employee, Shareholder)