< em > In Vitro < /em > and < em > In Vivo < /em > Characterization of Tebipenem (TBP), an Orally Active Carbapenem, against Biothreat Pathogens

Antimicrob Agents Chemother. 2021 Feb 16:AAC.02385-20. doi: 10.1128/AAC.02385-20. Online ahead of print.ABSTRACTBacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei 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 in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 - 0.008 μg/ml for B. anthracis, ≤0.0005 - 0.03 μg/ml for Y. pestis, 0.25 - 1 μg/ml for B. mallei, and 1 - 4 μg/ml for B. pseudomallei In a B. anthracis 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 c...

Source: Antimicrobial Agents and Chemotherapy - February 17, 2021 Category: Microbiology Authors: Nicholas P Clayton Akash Jain Stephanie A Halasohoris Lisa M Pysz Sanae Lembirik Steven D Zumbrun Christopher D Kane Michael J Hackett Denise Pfefferle M Autumn Smiley Michael S Anderson Henry Heine Gabriel T Meister Michael J Pucci Source Type: research