1041. In vitro activity of tebipenem against a recent collection of fastidious organisms recovered from respiratory tract infections
Authors: Arends S J Ryan , Klauer Abby L , Cotroneo Nicole , Critchley Ian A , Mendes Rodrigo E 
Published: December 2021

Abstract

Background
Tebipenem is under development as an oral treatment option for complicated urinary tract infections and acute pyelonephritis. This study further evaluated the in vitro activity of tebipenem against various fastidious organisms recovered from community-acquired respiratory tract infections (CARTIs).

Methods
The study included a total of 2,476 fastidious organisms: Haemophilus influenzae (692 isolates, including fluoroquinolone-resistant, β-lactamase-positive, and β-lactamase-negative ampicillin-resistant [BLNAR]), Haemophilus parainfluenzae (30 isolates, including β-lactamase-positive and BLNAR), Moraxella catarrhalis (490 isolates), and Streptococcus pneumoniae (1,264 isolates, including penicillin-resistant). The isolates were collected primarily from CARTIs (90.8%) and pneumonia in hospitalized patients (PIHPs, 9.2%). Organisms were tested using reference broth microdilution methods in a central laboratory.

Results
Tebipenem had MIC90 values of 0.5 mg/L against H. influenzae and 1 mg/L against H. parainfluenzae isolates. All 18 BLNAR isolates from these two species were inhibited at ≤1 mg/L of tebipenem. The MIC90 values observed for ertapenem and meropenem was 0.25 mg/L for these organisms. Tebipenem displayed good activity against M. catarrhalis (MIC90, 0.03 mg/L). Tebipenem inhibited 100% of S. pneumoniae isolates at ≤1 mg/L. Tebipenem activity (MIC90, 0.12 mg/L) was 8-fold greater than ertapenem (MIC90, 1 mg/L) against S. pneumoniae isolates.

Conclusion
Tebipenem displayed potent activity against fastidious organisms causing respiratory tract infections. Greater than 99.7% of all Haemophilus isolates, including all BLNAR, were inhibited at ≤1 mg/L. All M. catarrhalis isolates were inhibited at ≤0.03 mg/L. Although tebipenem activity correlated with penicillin resistance, all S. pneumoniae isolates were inhibited at ≤1 mg/L. Tebipenem in vitro activity was greater than ertapenem when tested against S. pneumoniae isolates. This data supports the possible development of tebipenem as an oral option for combating CARTIs caused by these organisms.
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Disclosures
S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L. Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)