Oral tebipenem pivoxil hydrobromide (HBr), a carbapenem, is as effective as intravenous (IV) ertapenem in treating complicated urinary tract infection (cUTI) and pyelonephritis in appropriately selected hospitalized patients, according to new study findings published in The New England Journal of Medicine.
“Tebipenem has broad-spectrum activity against multidrug-resistant gram-negative pathogens, including fluoroquinolone-resistant and ESBL-producing Enterobacterales,” Angela K. Talley, MD, of Spero Therapeutics, Cambridge, Massachusetts, and colleagues explained.
In the international phase 3 ADAPT-PO trial (ClinicalTrials.gov number, NCT03788967), the investigators randomly assigned 868 hospitalized patients diagnosed with cUTI (50.8%) or acute pyelonephritis (49.2%) due to gram-negative bacteria susceptible to a carbapenem to receive oral tebipenem HBr (600 mg every 8 hours) or IV ertapenem (1 g every 24 hours). Patients with a creatinine clearance of 31 to 50 mL/min received 300 mg of tebipenem HBr or placebo every 8 hours. Patients with a creatinine clearance of 30 mL/min or less were excluded.
More than 90% of the baseline pathogens were Enterobacterales, primarily Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Proteus mirabilis. Of the cohort, 11.5% had bacteremia and 19.7% had systemic inflammatory response syndrome.
After a 7-to-10-day course of antibiotic therapy (up to 14 days for patients with bacteremia), an overall response comprising clinical cure and microbiologic response occurred in 58.8% of the tebipenem HBr group and 61.6% of the ertapenem group – a 3.3% difference that was well within the noninferiority margin of 12.5%, Dr Talley and colleagues reported. Clinical cure at a test-of-cure visit was observed in 93.1% and 93.6%, respectively. Microbiologic response occurred in 59.5% and 63.5%, respectively.
Adverse events (AEs) occurred in 25.7% of the tebipenem HBr group and 25.6% of the ertapenem group. The most common AEs were mild diarrhea, nausea, and headache. Drug-related AEs occurred in 9.3% and 6.1%, respectively. C. difficile-associated AEs occurred in 3 patients receiving ertapenem, but no patients receiving tebipenem HBr.
Dr Talley’s team concluded, “In the absence of other effective oral agents, tebipenem pivoxil hydrobromide may provide an option for the treatment of complicated urinary tract infection and acute pyelonephritis due to antibiotic-resistant uropathogens.”
Disclosure: This research was supported by Spero Therapeutics. Please see the original reference for a full list of disclosures.
Eckburg PB, Muir L, Critchley IA, et al. Oral tebipenem pivoxil hydrobromide in complicated urinary tract infection. N Engl J Med. 386:1327-1338. Published online April 7, 2022. doi:10.1056/NEJMoa2105462