P-1214. In Vitro Antibacterial Spectrum and Activity of Tebipenem Against Enterobacterales Clinical Isolates Causing Urinary Tract and Bloodstream Infections in the United States and United Kingdom in 2023-2024

TL;DR

Tebipenem shows strong in vitro antibacterial activity against Enterobacterales causing UTIs and bloodstream infections in the US and UK, including drug-resistant strains.

Contribution

This study provides new in vitro data on tebipenem's effectiveness against clinical isolates, including those with ESBL and MDR phenotypes.

Findings

Tebipenem had MIC50 and MIC90 values of 0.015 and 0.06 μg/mL against 7,694 Enterobacterales isolates.

Tebipenem remained active against ESBL and MDR isolates with MIC50 and MIC90 values of 0.015 and 0.06-0.12 μg/mL.

Tebipenem's activity was comparable to IV carbapenems and superior to other drug classes like fluoroquinolones and cephalosporins.

Abstract

Tebipenem pivoxil hydrobromide (formerly SPR994) is in clinical development as potentially the first oral broad-spectrum carbapenem agent in the US for the treatment of complicated urinary tract infections (cUTI) and acute pyelonephritis (AP). This study reports on the in vitro activity of tebipenem and comparator agents tested against Enterobacterales isolates recovered from UTI and bloodstream infections (BSI) in the US.

Between 2023 and 2024, 7,694 Enterobacterales clinical isolates were collected from 72 medical centers in the US and UK. These included 73.5% (5,654) from UTI (54.8% (3101) outpatients; 28.7% (1624) inpatients, including 11% (179) hospital-acquired infections) and 26.5% (2,040) from BSI (22.4% (456) outpatients; 67% (1366) inpatients, including 19% (261) hospital-acquired infections). Isolates were tested for susceptibility by CLSI reference broth microdilution method. MIC results for comparator agents were interpreted using the most recent CLSI M100 (2025) breakpoint criteria.

Tebipenem MIC50 and MIC90 values against all 7,694 Enterobacterales isolates were 0.015 μg/mL and 0.06 μg/mL, respectively (UTI and BSI specific results are shown in the Table). Similar MIC50/90 values were obtained for ertapenem (MIC50/90, ≤0.008/0.06 μg/mL), imipenem (MIC50/90, ≤0.12/1 μg/mL), and meropenem (MIC50/90, 0.03/0.06 μg/mL). The susceptibility rates for recommended comparator agents were below 89% for levofloxacin (81.5%, MIC50/90, 0.06/8 μg/mL), ceftriaxone (82.7%, MIC50/90, ≤0.06/ >8 μg/mL), cefepime (88.3%, MIC50/90, 0.06/8 μg/mL, and trimethoprim-sulfamethoxazole (75.2%, MIC50/90, ≤0.12/ >4 μg/mL). Tebipenem remained active against isolates resistant to other agents, including ESBL or MDR phenotypes, with MIC50 and MIC90 values of 0.015 µg/mL and 0.06-0.12 µg/mL, respectively. Antibacterial agents from other drug classes showed susceptibility rates of between 0% and 67%.

Tebipenem had potent in vitro activity against a diverse set of Enterobacterales clinical isolates from the US, including those with ESBL and MDR phenotypes. These results indicate that tebipenem has activity comparable to IV carbapenems and can be a potential oral agent for treatment of cUTI and AP.

Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support Didem Torumkuney, PhD, GSK: Stocks/Bonds (Public Company) Ian A. Critchley, PhD, Spero Therapeutics: Stocks/Bonds (Public Company)

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