Tebipenem HBr
Carbapenems are an important subclass of antibiotics for the treatment of drug-resistant gram-negative bacterial infections. To date, carbapenems have emerged as the standard-of-care for many MDR gram-negative bacterial infections, but today they are only available as IV therapeutics for such indications.[6]
Spero is developing Tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994) as a potential oral antibiotic for the treatment of cUTI, including pyelonephritis, to help patients avoid hospitalizations (stay at home) and/or transition patients home after IV therapy (get home) if approved.
GSK and Spero plan to work with US regulatory authorities to include the data as part of a filing in 2H 2025. Full results will be submitted for presentation at an upcoming scientific congress and for publication in a peer-reviewed journal.
A Substantial Burden and Our Motivation to Succeed
Antibiotic resistance is a growing global health threat, and one particularly troubling concern is the rise in resistant strains of E. coli, which cause the majority of urinary tract infections (UTIs).[1,2,3] In a recent surveillance study conducted in the USA in 2022, 20.2% and 26.5% of isolates were resistant to levofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX), respectively.[SENTRY 2022] Of note, the nationwide prevalence of extended-spectrum β-lactamase (ESBL) phenotype amongst E. coli was 12.0% among UTI isolates and 14.6% among E. coli from all specimen sources in 2022. [SENTRY 2022]
Incidence Change Among Hospitalized Patients in the USA (2012 — 2017)[4]
ESBL-producing Enterobacterales infections were the only major MDR pathogens in the United States with an observed increase in incidence for hospitalized patients between 2012-2017, driven by the 64% increase in community-onset cases and primarily from E. coli.[4]
In vitro activity of oral antibiotics against non-ESBL- and ESBL-phenotype E. coli from urinary tract isolates (USA 2022)
This is concerning, as approximately 80% of cUTI cases initially seek care in the outpatient setting.[5] Recent Infectious Diseases Society of America guidance for the treatment of cUTI or pyelonephritis due to ESBL-producing Enterobacterales recommend treatment with an intravenous carbapenem, a fluoroquinolone, or TMP/SMX.[6] Unfortunately, high co-resistance among the currently available oral treatment options may limit the ability to treat some patients in an outpatient setting.[3,7,8,9]
Our engagement and collaboration with the scientific community reinforces our commitment to addressing the most critical unmet needs in infectious disease. Click to watch a short video of David Talan, MD, an infectious disease and emergency medicine physician, summarizing his surveillance research and the ongoing clinical challenges in treating patients with cUTI and pyelonephritis.
The Latest
In July 2023, Spero announced receiving FDA agreement under a Special Protocol Assessment (SPA) for the design of PIVOT-PO, a pivotal Phase 3 trial comparing oral tebipenem HBr with intravenous imipenem cilastatin in hospitalized adults with cUTI/AP. Enrollment began in early 2024, surpassing 60% by the end of that year.
In May 2025, Spero and its development partner GSK announced the PIVOT-PO trial was stopped early for efficacy, following a recommendation from an Independent Data Monitoring Committee (IDMC). The committee determined that tebipenem HBr had successfully met its primary endpoint, demonstrating non-inferiority to intravenous imipenem-cilastatin.
GSK plans to submit the trial data to the FDA for regulatory approval in the second half of 2025. If approved, tebipenem HBr could be the first oral carbapenem antibiotic in the U.S., potentially changing the treatment landscape for cUTI patients.
For more information on PIVOT-PO, refer to ClinicalTrials.gov ID NCT06059846.
Tebipenem HBr represents a promising step in helping to combat antibiotic-resistant infections.
Check out the latest posters and publications on tebipenem HBr:
Resources
World Health Organization (WHO)– antimicrobial resistance
The World Health Organization, an agency of the United Nations, was established in 1948 to promote health and control communicable diseases.
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The Centers for Disease Control and Prevention (CDC)
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services, and is headquartered in Atlanta, Georgia.[2][3] The agency's main goal is the protection of public health and safety through the control and prevention of disease, injury, and disability in the US and worldwide.[4] The CDC focuses national attention on developing and applying disease control and prevention. It especially focuses its attention on infectious disease, food borne pathogens, environmental health, occupational safety and health, health promotion, injury prevention, and educational activities designed to improve the health of United States citizens.
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American Society for Microbiology
Established in 1899, ASM is the home for microbial scientists from around the globe to connect, learn, discover, and prepare for the future.
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ClinicalTrials.gov
ClinicalTrials.gov is a database of clinical studies conducted worldwide. The community can follow the progress of tebipenem HBr as the candidate moves through clinical trials.ClinicalTrials.gov ID NCT06059846.
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- Flores-Mierles AL, et al. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015; 13(5):269-84.
- Castanheira M, et al. Variations in the occurrence of resistance phenotypes and carbapenemase genes Among Enterobacteriaceae in 20 years of the SENTRY Antimicrobial Surveillance Program. Open Forum Infect Dis. 2019; 6(Suppl 1):S23-S33.
- Critchley IA, et al. The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017. PLoS One. 2019; 14(12):e0220265.
- Jernigan JA, et al. Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012-2017. N Engl J Med. 2020; 382(14):1309-1319.
- Carreno JJ, et al. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infect Dis. 2020; 7(1):ofz536.
- Tamma PD, et al. Infectious Diseases Society of America Guidance on the treatment of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis. 2021; 72(7):1109-1116.
- Simmering J, et al. The increase in hospitalizations for urinary tract infections and the associated costs in the United States, 1998–2011. Open Forum Infec Dis. 2017; 4(1):ofw281.
- Talan D, et al. Emergence of extended-spectrum β-lactamase urinary tract infections among hospitalized emergency department patients in the United States. Ann Emerg Med. 2021; 77(1):32-43.
- Lodise TP, et al. Hospital admission patterns of adult patients with complicated urinary tract infections who present to the hospital by disease acuity and comorbid conditions: How many admissions are potentially avoidable? Am J Infect Control. 2021; S0196-6553(21)00382-5.
[Last updated July 2024]
