P-1213. Activity of Tebipenem Against Enterobacterales, Including Molecularly Characterized Clinical Isolates Causing Urinary Tract and Bloodstream Infections from the United States in 2023

TL;DR

This study evaluates the effectiveness of tebipenem, a potential oral antibiotic, against drug-resistant bacteria causing urinary tract and bloodstream infections in the US.

Contribution

The study provides new in vitro data on tebipenem's activity against molecularly characterized clinical isolates, including ESBL and carbapenemase producers.

Findings

Tebipenem showed high susceptibility against ESBL-producing isolates with MIC50/90 of 0.015/0.03 µg/mL.

Tebipenem's activity was comparable to IV carbapenems against clinical isolates from US medical centers.

Oral comparators had susceptibility rates below 81% against ESBL isolates.

Abstract

Tebipenem pivoxil hydrobromide (TBP) (formerly SPR994) is in clinical development as the potential 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 TBP and comparator agents against molecularly characterized Enterobacterales isolates recovered from UTI and bloodstream infections (BSI) in the US, including ESBL and carbapenemase (CP) producing isolates.

A total of 3,523 Enterobacterales isolates collected from the US in 2023 were included. (UTI, 74.2% (2,614), BSI, 25.8% (909)). Isolates were tested for susceptibility (S) by CLSI reference broth microdilution method. E. coli and K. pneumoniae with aztreonam (ATM), ceftazidime (CAZ), or ceftriaxone (CRO) MICs of ≥2 µg/mL, and P. mirabilis with cefpodoxime (CPD) or CAZ MICs of ≥2 µg/mL were classified as ESBL phenotype. Isolates with MIC ≥2 µg/mL for imipenem (IMI) and/or meropenem (MER), or ≥1 µg/mL for ertapenem (ERT), were categorized as carbapenem-nonsusceptible (CNSE) phenotype. Isolates that met these criteria were screened for plasmid-mediated AmpC (pAmpC), ESBL, and CP genes.

A total of 14.1% (496/3,523) of isolates were identified with an ESBL phenotype and 13.3% (471/3,523) were ESBL, CSE phenotype (Table). Of the latter, 91.7% (432/471) carried ESBL and/or pAmpC genes. TBP had MIC50/90 of 0.015/0.03 µg/mL against this subset, with those for IMI (MIC50/90, ≤0.12/0.5 µg/mL), MER (MIC50/90, 0.03/0.06 µg/mL) and ERT (MIC50/90, 0.03/0.12 µg/mL). The S to other comparators was below 81%. The CNSE phenotype accounted for only 1.6% (56/3,523) of isolates, and 39.3% (22/56) carried CP. TBP displayed MIC50/90 of 1/ >8 µg/mL. IMI (MIC50/90, 2/ >8 µg/mL), MER (MIC50/90, 1/ >32 µg/mL) and ERT (MIC50/90, 2/ >2 µg/mL) were active against 48%, 61% and 9% of the CNSE subset, respectively, while the S of oral comparators was ≤48%.

TBP displayed MICs similar to those for overall isolates against ESBL-producing Enterobacterales isolates from UTIs and BSIs in US medical centers. These results indicate that TBP has activity comparable to IV carbapenems and has the potential for use as oral treatment option for 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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