The US FDA approved Utebzi (tebipenem pivoxil) for complicated urinary tract infections (cUTIs), including pyelonephritis, in adults with limited or no alternative oral treatment options — marking the first oral carbapenem antibiotic to reach approval in the US market. The drug, developed by Cambridge, Massachusetts-based Spero Therapeutics (Nasdaq: SPRO) and licensed to GSK, addresses a population where multidrug-resistant pathogens have progressively eroded the utility of standard oral agents, historically forcing clinicians toward intravenous therapy and hospital admission.
Utebzi is indicated for cUTIs caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis. The approved regimen is 600 mg orally every six hours for seven to ten days, with dose adjustment for patients with reduced renal function. Tebipenem pivoxil is a prodrug that is hydrolyzed after absorption to the active carbapenem tebipenem, which inhibits bacterial cell wall synthesis by binding penicillin-binding proteins, including those associated with beta-lactam resistance in Gram-negative organisms.
The approval rests on results from PIVOT-PO (NCT06059846), a global, randomized, double-blind Phase III non-inferiority trial enrolling 1,690 hospitalized adults with cUTI or acute pyelonephritis. Patients received either tebipenem pivoxil 600 mg orally or imipenem-cilastatin 500 mg intravenously, each administered every six hours. The primary endpoint was composite overall response — defined as clinical cure plus microbiological eradication — at the test-of-cure visit approximately 17 days after first dose. Tebipenem pivoxil achieved a 58.5% overall success rate (261/446 participants) versus 60.2% for imipenem-cilastatin (291/483 participants), with an adjusted treatment difference of −1.3% (95% CI: −7.5%, 4.8%), meeting the pre-specified non-inferiority margin of −10%. The most frequently reported adverse events were diarrhea and headache, occurring in ≥3% of patients; both were mild or moderate and non-serious.