FDA Approves Utebzi, First Oral Carbapenem Therapy for Complicated UTIs

The FDA approved tebipenem pivoxil (Utebzi; Spero Therapeutics, GSK) tablets for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, caused by susceptible microorganisms in adults with limited or no alternative oral treatment options. This action makes tebipenem pivoxil the first oral carbapenem therapy for cUTIs.¹

A UTI is an infection in any part of the urinary system (eg, kidneys, ureters, bladder, urethra), although most infections involve the lower urinary tract—the bladder and the urethra. Women have a higher risk of contracting UTIs than men.¹

cUTIs can have more severe symptoms compared with uncomplicated UTIs, including pain in the lower back, fever, chills, nausea, and vomiting. cUTIs may be in the lower or upper urinary tract and are more likely to be caused by drug-resistant bacteria. Risk factors for cUTI include the following: indwelling catheters, ureteric stents, neurogenic bladder, obstructive uropathy, urinary retention, urinary diversion, kidney stones, diabetes, immune deficiency, urinary tract modification, and UTIs in patients following renal transplant.^1,2

Clinical Data Supporting Tebipenem Pivoxil’s Approval

The treatment’s safety and efficacy were evaluated in the randomized, double-blind, double-dummy, multicenter, multinational phase 3 clinical trial, PIVOT-PO (NCT06059846),³ which enrolled adults with cUTIs, including pyelonephritis. A total of 1690 hospitalized patients were randomly assigned to receive tebipenem pivoxil 600 mg orally every 6 hours or imipenem/cilastatin 500 mg intravenously (IV) every 6 hours for 7 to 10 days. Of this enrolled population, 929 patients were considered the intent-to-treat (ITT) population (446 receiving tebipenem pivoxil, 483 receiving imipenem/cilastatin).^3,4

The trial’s primary end point was overall response (clinical cure plus microbiological eradication) at test-of-cure (TOC) assessed in the ITT population. Secondary end points included the number of patients in the microbiologically evaluable population with overall, clinical, and microbiological responses at the TOC, end-of-treatment, and late follow-up visits; the frequency of treatment-emergent and serious adverse events (AEs); and the plasma concentration of tebipenem pivoxil.^1-4

According to data published in Open Forum Infectious Diseases, the overall response at TOC was approximately 58.5% in 261 participants who received tebipenem pivoxil vs 60.2% in 291 participants who received imipenem/cilastatin (adjusted treatment difference: −1.3% [95% CI, −7.5% to 4.8%]). The authors noted that tebipenem pivoxil’s safety profile was overall consistent with that of imipenem/cilastatin, with the 2 most frequent treatment-emergent AEs being diarrhea and headache.⁴

In June 2025, an interim analysis assessing efficacy and futility was reviewed by an independent data monitoring committee (IDMC), and the study was stopped for efficacy reasons. The investigators reported that the trial had met its primary end point of noninferiority of tebipenem pivoxil hydrobromide compared with IV imipenem/cilastatin. The IDMC review reported no new safety concerns beyond those identified in prior research.²

The FDA cautions of several possible AEs. The most common are diarrhea, headache, nausea, abdominal pain, increased liver enzymes, and, in some cases, Clostridioides difficile infection. It is not recommended that patients with allergic reactions to tebipenem pivoxil or other β-lactam antibacterials receive this treatment, nor should patients with primary or secondary carnitine deficiency or inborn metabolism errors that can result in clinically significant carnitine deficiency.¹

REFERENCES

1. FDA approves first oral carbapenem therapy for complicated urinary tract infections. FDA. June 17, 2026. Accessed June 1, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-carbapenem-therapy-complicated-urinary-tract-infections

2. McGovern G. Phase 3 PIVOT-PO trial evaluating tebipenem HBr in cUTIs ends early after meeting primary end point. Pharmacy Times. June 2, 2025. Accessed June 17, 2026. https://www.pharmacytimes.com/view/phase-3-pivot-po-trial-evaluating-tebipenem-hbr-in-cutis-ends-early-after-meeting-primary-end-point

3. A study of oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) compared to intravenous imipenem-cilastatin in participants with complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) (PIVOT-PO). ClinicalTrials.gov. Updated March 10, 2026. Accessed June 17, 2026. https://clinicaltrials.gov/study/NCT06059846

4. Hong DK, Ascioglu S, Bhatt N, et al. 173. Oral tebipenem pivoxil hydrobromide versus intravenous imipenem-cilastatin in patients with complicated urinary tract infections or acute pyelonephritis: efficacy and safety results from the phase 3 PIVOT-PO study. Open Forum Infect Dis. 2026;13(suppl 1):ofaf695.003. doi:10.1093/ofid/ofaf695.003