FDA Approves Utebzi as First Oral Carbapenem for Complicated UTIs

The FDA announced the approval of Utebzi (tebipenem pivoxil) for the treatment of complicated urinary tract infections (cUTIs) in adults, according to a news release.¹ Demonstrating significant efficacy among adults with cUTIs, like pyelonephritis, tebipenem pivoxil is now the first oral carbapenem option with this indication.

“With antibiotic resistance continuing to rise, patients and health care professionals need new treatment options,” Tony Wood, chief scientific officer with GSK, said to Market Screener.² “The approval of Utebzi provides the first and only oral carbapenem antibiotic for appropriate adults with cUTIs, a solution that could help reduce reliance on hospital-based intravenous care and support efforts to address resistant infections.”

Complicated UTIs represent a significant health care burden, characterized by infections that have spread beyond the bladder to include pyelonephritis or cases involving systemic symptoms such as fever, chills, and bacteremia. According to a report in US Pharmacist, these infections lead to over 626,000 hospital admissions annually in the US, with an estimated total economic impact exceeding $6 billion per year.^2,3

The majority of these cases are attributed to bacteria that colonize the colon, with gram-negative organisms like Escherichia coli and Klebsiella pneumoniae serving as the most common uropathogens.^3,4

READ MORE: First-in-Class Oral Therapy Is Approved for Uncomplicated Urinary Tract Infection

The rise of superbugs—bacteria that have adapted to typically effective medicines—has made managing these infections increasingly difficult. Cleveland Clinic notes that pathogens like ESBL-producing E. coli use enzymes to break down standard antibiotics, turning a routine infection into one that is difficult to treat and potentially life-threatening.⁴

Although carbapenems have long been viewed as a last-resort treatment for these resistant gram-negative uropathogens, their use was historically limited to intravenous administration, which increased hospital resource use and often reduced patient quality of life.^2,4,5

The FDA’s decision was underpinned by data from the PIVOT-PO (NCT06059846) phase 3 trial, a global, randomized, double-blind, noninferiority study that compared oral tebipenem pivoxil to intravenous imipenem-cilastatin. The trial, which enrolled 1690 hospitalized participants, demonstrated that tebipenem pivoxil was noninferior to the intravenous standard of care.^1,2,6

Specifically, tebipenem pivoxil achieved a 58.5% overall success rate at the test-of-cure visit, compared with 60.2% for the imipenem-cilastatin group. This clinical noninferiority is a critical data point for pharmacists who must ensure that shifting to an oral regimen does not compromise patient outcomes.^2,6

Pharmacists are expected to play an integral role in the collaborative selection of appropriate empiric antimicrobial therapy. Under the 2025 IDSA guideline updates, clinicians are encouraged to use a 4-step approach when managing cUTIs: assessing the severity of illness, considering resistance risk factors, evaluating patient-specific factors, and utilizing local antibiograms for patients with sepsis.³

Tebipenem pivoxil fits into this framework specifically for adults who have limited or no alternative oral treatment options. However, stewardship remains paramount to combat the global health problem of antibiotic resistance.^1,4

A systematic review published in the Journal of Infection and Chemotherapy suggests that while carbapenems are highly effective, alternative noncarbapenem antibiotics, such as siderophore cephalosporins or novel beta-lactamase inhibitor combinations, may offer similar efficacy for targeted therapy once susceptibility data are available.⁵

Pharmacists can use this information to lead de-escalation strategies, preserving carbapenems for the most difficult-to-treat pathogens. When dispensing or recommending tebipenem pivoxil, pharmacists must be vigilant regarding specific patient eligibility criteria.^3,5

Clinical trial protocols excluded patients with a creatinine clearance of 30 mL/min or less, as well as those with a history of epilepsy, known seizure disorders, or genetic metabolism anomalies associated with carnitine deficiency. Safety data indicate that the most common adverse events reported in trial participants included diarrhea, headache, nausea, and abdominal pain.^1,2,6

Pharmacists should also counsel patients to monitor for serious complications such as Clostridioides difficile infection or signs of increased liver enzymes. Furthermore, the transition to oral therapy is only appropriate for patients who are hemodynamically stable, clinically improving within 48 to 72 hours of effective therapy, and able to absorb oral medications.^1,3

By shifting care to the outpatient setting, tebipenem pivoxil has the potential to improve patient experiences and reduce hospital resource utilization. This milestone for Spero Therapeutics and GSK reflects over a decade of dedication and was supported in part by federal funds from the Biomedical Advanced Research and Development Authority (BARDA).²

As this new therapy becomes available to the public, the expertise of pharmacists will be essential in navigating its use within the broader effort to protect the existing antibiotic toolkit.^3,4

“Pharmacists play an integral role in complicated UTIs by working collaboratively with clinicians to select the most appropriate empiric antimicrobial therapy regimen based on patient-specific factors,” concluded US Pharmacist.³ “Pharmacists can educate the public and other health care professionals about the updated recommendations for complicated UTIs, including assessing a patient’s eligibility for an oral antibiotic and appropriate therapy duration.”

READ MORE: Infectious Disease Resource Center

REFERENCES

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

2. GSK: Utebzi (tebipenem pivoxil) approved in the US for adults with complicated urinary tract infections (cUTIs). Market Screener. June 17, 2026. Accessed June 17, 2026. https://www.marketscreener.com/news/gsk-utebzi-tebipenem-pivoxil-approved-in-the-us-for-adults-with-complicated-urinary-tract-infect-ce7f5cdcd188f623

3. Atmar A, Hernandez C, Sucher A. Management of complicated urinary tract infections. US Pharmacist. April 16, 2026. Accessed June 17, 2026. https://www.uspharmacist.com/article/management-of-complicated-urinary-tract-infections

4. Antibiotic resistance. Cleveland Clinic. October 19, 2023. Accessed June 17, 2026. https://my.clevelandclinic.org/health/articles/21655-antibiotic-resistance

5. Maeda M, Sunaga T, Sato MT, et al. Efficacy of carbapenems and alternative antimicrobials for treating complicated urinary tract infections caused by third-generation cephalosporin-resistant gram-negative bacteria: a systematic review and meta-analysis of randomised controlled trials. J Infect Chemother. 2024;30(11):1147-1155. https://doi.org/10.1016/j.jiac.2024.05.001

6. 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. Accessed June 17, 2026. https://clinicaltrials.gov/study/NCT06059846