FIRST ORAL CARBAPENEM ANTIBIOTIC APPROVED FOR COMPLICATED UTIS
Utebzi (tebipenem pivoxil) is the first oral carbapenem approved in the U.S.
Straight Healthcare
August 2026
August 2026
Carbapenems are among the most potent antibiotics available, reserved for infections caused by resistant gram-negative organisms, including many extended-spectrum beta-lactamase (ESBL)-producing strains. Until now, every carbapenem approved in the U.S. (imipenem-cilastatin, meropenem, ertapenem, doripenem) required intravenous administration, limiting their use. The FDA recently approved Utebzi (tebipenem pivoxil), an oral prodrug that is converted to the active carbapenem tebipenem after absorption, making it the first oral carbapenem available in the U.S. Like other carbapenems, tebipenem binds penicillin-binding proteins to inhibit bacterial cell wall synthesis. It is indicated for complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible E. coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis in adults with limited or no alternative oral options.
Approval was based on PIVOT-PO, a global, randomized, double-blind, non-inferiority trial that enrolled 1,690 hospitalized adults with cUTI or pyelonephritis. Patients were randomized to oral Utebzi 600 mg every 6 hours or IV imipenem-cilastatin 500 mg every 6 hours for 7 to 10 days. In the microbiological intent-to-treat population (N=929), composite response (clinical cure plus microbiological eradication) at test-of-cure was 58.5% with Utebzi versus 60.2% with imipenem-cilastatin (treatment difference −1.3%; 95% CI −7.5 to 4.8), meeting the non-inferiority margin. Dosing is 600 mg (two 300 mg tablets) every 6 hours for patients with an eGFR of 60–150 ml/min, with reduced doses for lower eGFR. Common adverse reactions included diarrhea (8%), headache (3%), and nausea (1%). Utebzi is contraindicated in patients with beta-lactam hypersensitivity or carnitine deficiency, since its pivalate moiety can cause carnitine depletion with prolonged use. Seizures and other CNS reactions have occurred with carbapenems, including Utebzi, particularly in patients with CNS disorders, a seizure history, or renal impairment. Concomitant valproic acid or divalproex should be avoided, as carbapenems can lower valproate levels and provoke breakthrough seizures; OAT1/3 inhibitors such as probenecid increase tebipenem exposure.
Utebzi gives prescribers an oral option for cUTI and pyelonephritis that avoids hospitalization for carbapenem-level coverage. However, given the importance of preserving carbapenem susceptibility, it is important to reserve Utebzi for infections resistant to first-line oral agents, such as fluoroquinolones, rather than using it as an initial empiric choice.
Approval was based on PIVOT-PO, a global, randomized, double-blind, non-inferiority trial that enrolled 1,690 hospitalized adults with cUTI or pyelonephritis. Patients were randomized to oral Utebzi 600 mg every 6 hours or IV imipenem-cilastatin 500 mg every 6 hours for 7 to 10 days. In the microbiological intent-to-treat population (N=929), composite response (clinical cure plus microbiological eradication) at test-of-cure was 58.5% with Utebzi versus 60.2% with imipenem-cilastatin (treatment difference −1.3%; 95% CI −7.5 to 4.8), meeting the non-inferiority margin. Dosing is 600 mg (two 300 mg tablets) every 6 hours for patients with an eGFR of 60–150 ml/min, with reduced doses for lower eGFR. Common adverse reactions included diarrhea (8%), headache (3%), and nausea (1%). Utebzi is contraindicated in patients with beta-lactam hypersensitivity or carnitine deficiency, since its pivalate moiety can cause carnitine depletion with prolonged use. Seizures and other CNS reactions have occurred with carbapenems, including Utebzi, particularly in patients with CNS disorders, a seizure history, or renal impairment. Concomitant valproic acid or divalproex should be avoided, as carbapenems can lower valproate levels and provoke breakthrough seizures; OAT1/3 inhibitors such as probenecid increase tebipenem exposure.
Utebzi gives prescribers an oral option for cUTI and pyelonephritis that avoids hospitalization for carbapenem-level coverage. However, given the importance of preserving carbapenem susceptibility, it is important to reserve Utebzi for infections resistant to first-line oral agents, such as fluoroquinolones, rather than using it as an initial empiric choice.
- Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection, N Engl J Med (2022) [PubMed abstract]
- Tebipenem (Utebzi) review
