1041. In vitro activity of tebipenem against a recent collection of fastidious organisms recovered from respiratory tract infections

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. Table 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)

. 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) Background. Microbiota-based treatments have shown promise to reduce recurrence, morbidity, and mortality for recurrent Clostridioides difficile infections (rCDI), but consistent and reliable safety data are needed to support regulatory approvals and broaden patient access. Here we provide cumulative safety data from 5 prospective clinical studies evaluating RBX2660-a standardized, microbiota-based investigational live biotherapeutic-for reducing rCDI.
Methods. This analysis included three Phase 2 (PUNCH CD, PUNCH CD2, PUNCH CD Open Label) and two Phase 3 trials (PUNCH CD3, PUNCH CD3-OLS ad hoc analysis). Participants were ≥18 years old with documented rCDI who completed standard-of-care oral antibiotic therapy prior to treatment with RBX2660. PUNCH CD3-OLS allowed participants with comorbidities of irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). Depending on the trial, assigned study treatment was 1 or 2 doses of RBX2660 (or placebo), administered rectally. Participants whose CDI recurred within 8 weeks were eligible for additional RBX2660 treatment. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; CD2 and CD Open Label recorded TEAEs for 24 months.
Conclusion. Across five clinical studies with consistent investigational product, RBX2660 was well-tolerated in rCDI participants. In aggregate, this data provides compelling and consistent safety data for RBX2660.

Session: P-59. New Drug Development
Background. Mecillinam is a β-lactam antibiotic that exerts its antibacterial activity by binding to penicillin-binding protein 2. In the USA, intravenous (IV) mecillinam is in development for the treatment of complicated UTIs in the hospital setting and as step-down therapy transitioning from IV mecillinam to oral pivmecillinam so that patients can continue treatment at home. To support the clinical development of mecillinam in the USA for the treatment of both complicated and uncomplicated UTI, this observational study investigated the activity of mecillinam against Enterobacterales isolates from patients with UTI in the USA, collected during 2019.
Methods. This study evaluated the activity of mecillinam and other antimicrobial agents against 1075 selected Enterobacterales clinical isolates collected from patients with UTI in the USA during 2019. Antibiotic activity (minimum inhibitory concentration [MIC]) was determined by Clinical & Laboratory Standards Institute (CLSI) agar dilution methodology, and susceptibility was interpreted according to CLSI guidelines.
Results. Among the selected 1075 isolates, producers of extended-spectrum beta-lactamase (ESBL) represented 9.6% of Escherichia coli and 50% of Klebsiella pneumoniae. Ninety-five percent of the isolates tested were susceptible to mecillinam ( Table  1). The MIC 50 and MIC 90 values for mecillinam were 0.25 and 2 µg/mL, respectively. Fosfomycin MIC 50 and MIC 90 were 1 and 32 µg/mL, respectively (97.6% of isolates