Phase 3 results for tebipenem HBr suggest an oral carbapenem could provide an effective alternative to IV therapy for multidrug-resistant UTIs.
New phase 3 data presented at IDWeek 2025 in Atlanta, Georgia, demonstrated that tebipenem HBr, an investigational oral antibiotic, was non-inferior to intravenous (IV) imipenem-cilastatin for treating complicated urinary tract infections (cUTIs), including pyelonephritis. The findings from the pivotal PIVOT-PO trial were announced by GSK and Spero Therapeutics and mark an important advance toward a potential oral option for patients who currently rely on IV carbapenems.1
The phase 3, randomized, double-blind PIVOT-PO trial (NCT06059846) compared oral tebipenem HBr (600 mg every six hours) to IV imipenem-cilastatin (500 mg every six hours) in hospitalized adults with cUTI or pyelonephritis. The study enrolled 1,690 participants globally and was stopped early for efficacy in May 2025 after meeting its primary endpoint.
At the test-of-cure visit, tebipenem HBr achieved a 58.5% overall response rate—defined as clinical cure plus microbiological eradication—compared with 60.2% for imipenem-cilastatin (adjusted treatment difference: −1.3%; 95% CI: −7.5%, 4.8%), confirming non-inferiority. Clinical cure rates were 93.5% for tebipenem HBr and 95.2% for imipenem-cilastatin, while microbiological response rates were 60.3% and 61.3%, respectively. Results were consistent among patients infected with antimicrobial-resistant Enterobacterales.
Tebipenem HBr matched IV imipenem-cilastatin in efficacy and safety for cUTI treatment.
The oral formulation could reduce hospital stays and IV antibiotic use.
Approval would mark the first U.S. oral carbapenem option for resistant infections.
The safety profile of tebipenem HBr was comparable to that of imipenem-cilastatin and other carbapenem antibiotics. The most common adverse events (≥3%) were diarrhea and headache, all of which were mild or moderate and non-serious.
“Increasing antibiotic resistance among community-acquired bacteria that cause cUTIs is greatly amplifying the burden of treatment for patients, clinicians, and payers,” said Dr. George Sakoulas, adjunct professor in the Department of Pediatrics at UCSD School of Medicine and chief of infectious diseases at Sharp Rees-Stealy Medical Group. “The therapeutic flexibility of a new oral antibiotic may reduce the need for intravenous antibiotics to treat cUTI, providing benefit to patients and improving treatment options.”
Complicated urinary tract infections represent a major global and domestic health challenge, with an estimated 2.9 million cases treated annually in the United States alone. These infections are frequently caused by multidrug-resistant bacteria and are associated with serious complications, including sepsis, organ failure, and death. They also impose a significant healthcare burden, contributing to more than $6 billion in costs annually.
A 2025 World Health Organization report on antimicrobial resistance (AMR) found that resistance rates in urinary pathogens continue to rise globally, undermining the effectiveness of first-line and hospital-based therapies. The availability of an oral carbapenem could help reduce reliance on IV antibiotics, potentially alleviating hospital capacity strain and improving patient quality of life.2
According to the press release, GSK plans to submit the tebipenem HBr data to the FDA in the fourth quarter of 2025. If approved, tebipenem HBr would become the first oral carbapenem available in the United States—offering a more flexible treatment option for patients with complicated UTIs and addressing an urgent need in an era of rising resistance.1
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