Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection

作者：Paul B. Eckburg, Lori A Muir, Ian A. Critchley, Susannah M. Walpole, Hanna Kwak, Anne-Marie Phelan, Gary Moore, Akash Jain, Tim Keutzer, Aaron Dane, David Melnick, Angela K. Talley · 发表于：New England Journal of Medicine · 年份：2022 · DOI：10.1056/nejmoa2105462 · 被引用次数：78 · 研究领域：Antibiotics Pharmacokinetics and Efficacy、Urinary Tract Infections Management、Antibiotic Resistance in Bacteria

BACKGROUND: There is a need for oral antibiotic agents that are effective against multidrug-resistant gram-negative uropathogens. Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem with activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase-producing and fluoroquinolone-resistant strains. METHODS: In this phase 3, international, double-blind, double-dummy trial, we evaluated the efficacy and safety of orally administered tebipenem pivoxil hydrobromide as compared with intravenous ertapenem in patients with complicated urinary tract infection or acute pyelonephritis. Patients were randomly assigned, in a 1:1 ratio, to receive oral tebipenem pivoxil hydrobromide (at a dose of 600 mg every 8 hours) or intravenous ertapenem (at a dose of 1 g every 24 hours) for 7 to 10 days (or up to 14 days in patients with bacteremia). The primary efficacy end point was overall response (a composite of clinical cure and favorable microbiologic response) at a test-of-cure visit (on day 19, within a ±2-day window) in the microbiologic intention-to-treat population. The noninferiority margin was 12.5%. RESULTS: A total of 1372 hospitalized adult patients were enrolled; 868 patients (63.3%) were included in the microbiologic intention-to-treat population (50.8% of whom had complicated urinary tract infections and 49.2% of whom had pyelonephritis). An overall response was seen in 264 of 449 patients (58.8%) who received tebipenem pivoxil hydrobro...