FDA Approves First Oral Carbapenem Antibiotic for Complicated UTIs

Yesterday, the FDA approved the oral antibiotic tebipenem pivoxil (Utebzi; GSK and Spero Therapeutics) for the treatment of complicated urinary tract infections (UTIs), including pyelonephritis, in adults with limited or no alternative oral treatment options, making it the first and only oral carbapenem antibiotic to receive this indication.¹

New Oral Alternative May Reduce Reliance on Intravenous Antibiotics

More than 3 million cases of complicated UTIs are reported in the US each year, with treatment failure affecting up to 34% of patients. As a result, these infections account for over $6 billion per year in health care costs, driven by recurrent infections, complications, and hospital utilization.

While carbapenems are the standard treatment option for severe or resistant infections, they have historically only been available in intravenous formulations. Consequently, treatment increased hospital resource use and impacted patient quality of life.

The FDA’s decision introduces tebipenem pivoxil as the first oral carbapenem antibiotic for this population, offering a potential alternative that may enable treatment outside the hospital setting and reduce reliance on intravenous therapy.

“With antibiotic resistance continuing to rise, patients and health care professionals need new treatment options,” Tony Wood, chief scientific officer at GSK, said in a news release. “The approval of Utebzi provides the first and only oral carbapenem antibiotic for appropriate adults with complicated UTIs, a solution that could help reduce reliance on hospital-based intravenous care and support efforts to address resistant infections.”

Tebipenem pivoxil is expected to be available to US patients nationwide by the end of 2026.

“Through our partnership with GSK, we look forward to this much-needed oral treatment option reaching [complicated] UTI patients to help reduce the burden of the disease,” Esther Rajavelu, president and CEO of Spero Therapeutics, said in a news release.

Phase 3 PIVOT-PO Findings Confirm Efficacy, Safety of Tebipenem Pivoxil

The approval was supported by data from the phase 3, global, randomized, double-blind, double-dummy, noninferiority PIVOT-PO trial (NCT06059846), which evaluated tebipenem pivoxil against intravenous imipenem-cilastatin in hospitalized patients with complicated UTIs.² A total of 1690 patients were randomly assigned to receive either tebipenem pivoxil 600 mg orally or imipenem-cilastatin 500 mg intravenously every 6 hours for 7 to 10 days.³

Of these patients, 929 comprised the intent-to-treat population used for efficacy analyses. In this population, efficacy was assessed using a combined measure of clinical cure, defined as resolution of infection signs and symptoms, and microbiological response, defined as a reduction in baseline pathogens at follow-up.

The trial demonstrated noninferiority of tebipenem pivoxil vs intravenous imipenem-cilastatin based on the overall response at the test-of-cure visit.¹ Specifically, tebipenem pivoxil achieved a 58.5% overall success rate (261/446) compared with 60.2% (291/483) for imipenem-cilastatin (adjusted treatment difference, −1.3%; 95% CI, −7.5% to 4.8%).

The safety profile was generally comparable between treatment groups and consistent with the known profile of carbapenem antibiotics. The most frequently reported adverse events were diarrhea and headache. Others included nausea, abdominal pain, increased liver enzymes, and Clostridioides difficile infection. However, these events were all mild to moderate and nonserious.

“For patients with complicated UTIs and their caregivers, this approval is a major milestone as today’s standard of care places a serious burden on them and hospitals,” Bilal Chughtai, MD, chief of urology at Northwell Plainview Hospital, said in a news release. “A new effective oral treatment offering an alternative option to intravenous care has the potential to enable more treatment in the outpatient settings, with the ambition to improve their experience.”

References

1. Utebzi (tebipenem pivoxil) approved in the US for adults with complicated urinary tract infections (cUTIs). News release. GSK. June 17, 2026. Accessed June 18, 2026. https://www.gsk.com/en-gb/media/press-releases/utebzi-tebipenem-pivoxil-approved-in-the-us-for-adults-with-complicated-urinary-tract-infections-cutis/
2. A study of oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) compared to intravenous imipenem-cilastatin in participants with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP) (PIVOT-PO). ClinicalTrials.gov. Last updated March 10, 2026. Accessed June 18, 2026. https://clinicaltrials.gov/study/NCT06059846
3. FDA approves first oral carbapenem therapy for complicated urinary tract infections. News release. FDA. June 17, 2026. Accessed June 18, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-oral-carbapenem-therapy-complicated-urinary-tract-infections