Oral tebipenem pivoxil hydrobromide noninferior to IV ertapenem for complicated UTI: NEJM
USA: Oral tebipenem pivoxil hydrobromide is noninferior and has a similar safety profile to intravenous ertapenem in the treatment of complicated urinary tract infection, says a recent study published in the New England Journal of Medicine.
Oral antibiotic agents that are effective against multidrug-resistant gram-negative uropathogens are needed. Tebipenem pivoxil hydrobromide is an orally bioavailable carbapenem that has activity against uropathogenic Enterobacterales, including extended-spectrum beta-lactamase–producing and fluoroquinolone-resistant strains.
Considering the above, Paul B. Eckburg and colleagues aimed to evaluate oral tebipenem pivoxil hydrobromide against IV ertapenem in hospitalized patients with complicated urinary tract infection or acute pyelonephritis in a phase 3, international, double-blind, double-dummy trial.
Patients were randomly assigned in the ratio of 1:1 to receive oral tebipenem pivoxil hydrobromide (at a dose of 600 mg every 8 hours) or IV ertapenem (at a dose of 1 g every 24 hours) for 7 to 10 days (or up to 14 days in patients with bacteremia).
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 was the primary efficacy end point.
The study led to the following findings:
· 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 hydrobromide, as compared with 258 of 419 patients (61.6%) who received ertapenem (weighted difference, −3.3 percentage points).
· Clinical cure at the test-of-cure visit was observed in 93.1% of the patients in the microbiologic intention-to-treat population who received tebipenem pivoxil hydrobromide and 93.6% of patients who received ertapenem (weighted difference, −0.6 percentage point); the majority of patients with microbiologic response failures at the test-of-cure visit were asymptomatic patients with recurrent bacteriuria.
· Secondary and subgroup analyses were supportive of the primary analysis.
· Adverse events were observed in 25.7% of patients who received tebipenem pivoxil hydrobromide and in 25.6% of patients who received ertapenem; the most common adverse events were mild diarrhea and headache.
To conclude, oral tebipenem pivoxil hydrobromide is noninferior to IV ertapenem in the treatment of complicated urinary tract infection and acute pyelonephritis and had a similar safety profile.
Reference:
The study titled, "Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection," was published in the New England Journal of Medicine.
DOI: 10.1056/NEJMoa2105462
KEYWORDS: NEJM, antibiotics, urinary tract infection, complicated UTI, oral tebipenem pivoxil hydrobromide, intravenous, IV, ertapenem, Paul B Eckburg, acute pyelonephritis
