and Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens.

and , causative pathogens for anthrax and plague, respectively, along with and are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacterales. We evaluated the activity and efficacy of tebipenem against biothreat pathogens. Tebipenem was active against 30-strain diversity sets of , , and with minimum inhibitory concentration (MIC) values of 0.001 - 0.008 μg/ml for , ≤0.0005 - 0.03 μg/ml for , 0.25 - 1 μg/ml for , and 1 - 4 μg/ml for In a murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.