Clinical question: Is oral carbapenem tebipenem effective in treating complicated urinary tract infections (UTIs)?
Background: Antimicrobial resistance among pathogens, especially gram-negative organisms, is increasing worldwide. Extended-spectrum beta-lactamase-producing and fluoroquinolone-resistant Enterobacteriaceae have become limited to no oral antibiotic options, posing a clinical and financial concern due to the need for inpatient treatment with intravenous agents.
Study design: Phase 3, randomized, double-blind, double-dummy, noninferiority trial
Setting: 95 centers in Central and Eastern Europe, South Africa, and the U.S.
Synopsis: 1,372 hospitalized adult patients with complicated UTI or acute pyelonephritis were randomly assigned in a 1:1 ratio to either receive oral tebipenem (plus intravenous placebo) or intravenous ertapenem (plus oral placebo) for 7-10 days (14 days in patients with bacteremia). Patients with severe hepatic and renal impairment, septic shock, or immunocompromised state were excluded. Approximately half the participants had complicated UTIs in each group. About 70% in the tebipenem group and 66% in the ertapenem group had bacteremia. The primary efficacy endpoint was a composite of clinical cure and favorable microbiologic response at a test-of-cure visit on day 19 (±2 days). Clinical cure at the test-of-cure visit was observed in 93.1% of the patients who received tebipenem versus 93.6% of patients who received ertapenem (weighted difference, -0.6 percentage point; 95% CI, -4.0 to 2.8). The overall incidence of adverse effects was about 26% in both groups. Most participants were enrolled from Europe, thus organism strains and resistance patterns may differ from other countries.
Bottom line: Oral tebipenem is non-inferior to intravenous ertapenem in the treatment of complicated UTIs and acute pyelonephritis.
Citation: Eckburg PB, et al. Oral tebipenem pivoxil hydrobromide in complicated urinary tract infection. N Engl J Med. 2022;386(14):1327-38.
Dr. Modha is a staff physician in the department of hospital medicine at the Cleveland Clinic, Cleveland, and an assistant professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University of Medicine.