Orapenem (tebipenem pivoxil) / Spero Therap, Meiji Seika, GSK - LARVOL DELTA

Refined Pharmacokinetic/Pharmacodynamic (PK/PD) Targets to Support Oral Tebipenem (TBP) Treatment for Complicated Urinary Tract Infections (cUTI) (IDWeek 2026) - No abstract available

PK/PD data • Infectious Disease

Pharmacokinetic-Pharmacodynamic and Exposure-Response Assessment of Oral Tebipenem in Patients with Complicated Urinary Tract Infections Including Acute Pyelonephritis (IDWeek 2026) - No abstract available

Clinical • PK/PD data • Infectious Disease

Human Simulated Dosing Regimens of Tebipenem Were Effective in a Rat Pyelonephritis Model against 16 Enterobacterales (IDWeek 2026) - No abstract available

Preclinical • Infectious Disease

Tebipenem Trial in Children With Shigellosis (clinicaltrials.gov) - P2 | N=132 | Completed | Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh | Active, not recruiting ➔ Completed

Head-to-Head • Trial completion

Pearls and pitfalls of oral carbapenem/penem agents: the promise of a new era or the risk of amplified resistance? (PubMed, Expert Opin Pharmacother) - "This review examines the chemistry, pharmacokinetics/pharmacodynamics, and phase 3 trial evidence for tebipenem and sulopenem, recently FDA-approved for urinary tract infections (UTI). This risk requires strict resistance surveillance and formulary restriction to confirmed MDR infections lacking oral alternatives. Their clinical trajectory will depend less on intrinsic activity than on the rigor of AMS frameworks governing their use."

Journal • Infectious Disease • Nephrology

Tebipenem pivoxil. (PubMed, Am J Health Syst Pharm) - No abstract available

Journal

The changing picture of community acquired urinary tract infections in the US: a daunting prospect. (PubMed, Expert Rev Anti Infect Ther) - "Resistance to fluoroquinolones and trimethoprim-sulfamethoxazole exceeding 40% among uropathogenic Escherichia coli - driven largely by multidrug-resistant and extended‑spectrum β‑lactamase (ESBL) - producing Enterobacterales strains such as ST131-are fueling increased reliance on parenteral agents, emergency department visits, and hospitalizations...It highlights oral agents approved or under review in the US, including pivmecillinam, sulopenem, and gepotidacin, each approved for uncomplicated UTI, as well as tebipenem pivoxil hydrobromide, which if approved, would represent the first oral carbapenem option for selected complicated UTIs, and discusses antimicrobial stewardship principles for community UTI management...Pharmacoeconomic analyses incorporating avoided admissions and patient convenience will be essential. Judiciously deployed within stewardship frameworks, these agents have potential to reduce the clinical and economic burden of multidrug-resistant UTI,..."

Journal • Review • Infectious Disease • Nephrology

GSK…and Spero Therapeutics…announced that the US Food and Drug Administration (FDA) has approved Utebzi, an oral antibiotic for the treatment of complicated urinary tract infections (cUTIs) including pyelonephritisa, caused by certain susceptible pathogensb in adult patients who have limited or no alternative oral treatment options (GSK Press Release) - "This approval is supported by positive results from the PIVOT-PO phase III trial, which demonstrated non-inferiority of tebipenem pivoxil compared to intravenous imipenem-cilastatin in hospitalised patients with cUTI, including pyelonephritis, based on the overall response (composite of clinical cure plus microbiological eradication) at the test of cure visit....Tebipenem pivoxil is anticipated to be made available to US patients by the end of 2026."

FDA approval • Launch US • Infectious Disease

In vitro and in vivo antibacterial activity of oral tebipenem in combination with novel β-lactamase inhibitors (avibactam, relebactam, vaborbactam) against KPC-producing Enterobacterales. (PubMed, Eur J Clin Microbiol Infect Dis) - "The combinations of oral TEB and novel β-lactamase inhibitors exhibit a potent antibacterial activity against KPC-producing Enterobacterales isolates in vitro and in vivo. Their potency is comparable to that of CAZ-AVI, and they even demonstrate potential efficacy against CAZ-AVI-resistant isolates. These findings provide a theoretical basis for the clinical management of CRE infections. Additionally, this combination serves as a viable step-down therapeutic option potentially facilitating earlier hospital discharge."

Journal • Preclinical • Infectious Disease

Resistance of Uropathogens to Tebipenem: An Analysis of the Evidence from In Vitro Antimicrobial Susceptibility Studies. (PubMed, Microorganisms) - "Two studies (22.2%) evaluated the activity of tebipenem against Enterococcus faecalis, with MIC90 of 1 mg/L among vancomycin-susceptible isolates and 32 mg/L in isolates with not-reported mechanisms of resistance. Tebipenem could be effective for outpatient treatment of infections caused by MDR Gram-negative pathogens. However, given its potential to exert selective pressure for the development of antimicrobial resistance, it should be considered for patients with cUTIs when none of the first-line treatment options demonstrate in vitro antimicrobial activity."

Journal • Preclinical • Review • Infectious Disease • Pneumonia

Impact of acquired broad-spectrum _xFFFF_-lactamases on susceptibility to oral cephalosporin (ceftibuten) and oral carbapenem (tebipenem) in combination with new _xFFFF_-lactamase inhibitors ledaborbactam and xeruborbactam in Escherichia coli (ESCMID Global 2026) - No abstract available

Combination therapy

Comparison of in vitro antimicrobial activity of tebipenem, sulopenem, meropenem, and ertapenem against cefotaxime-resistant Enterobacterales (ESCMID Global 2026) - No abstract available

Preclinical

In vitro activity of tebipenem against baseline Enterobacterales phenotypes and genotypes recovered from the phase III PIVOT-PO clinical trial for complicated urinary tract infections or acute pyelonephritis (ESCMID Global 2026) - No abstract available

P3 data • Preclinical • Infectious Disease • Nephrology

Oral tebipenem pivoxil tablets and intravenous imipenem-cilastatin efficacy by baseline uropathogen phenotypes and genotypes from the phase III PIVOT-PO clinical trial for complicated urinary tract infections or acute pyelonephritis (ESCMID Global 2026) - No abstract available

Clinical • P3 data • Infectious Disease • Nephrology

Impact of acquired broad-spectrum β-lactamases on susceptibility to oral cephalosporin (ceftibuten) and oral carbapenem (tebipenem) in combination with new β-lactamase inhibitors ledaborbactam and xeruborbactam in Escherichia coli (ESCMID Global 2026) - No abstract available

Combination therapy

Activity of tebipenem against Enterobacterales, including molecularly characterised isolates causing urinary tract and bloodstream infections in the United States and United Kingdom in 2023-2024 (ESCMID Global 2026) - No abstract available

Infectious Disease

Subgroup analysis of tebipenem pivoxil efficacy in patients with complicated urinary tract infection or acute pyelonephritis: results from the phase III PIVOT-PO study (ESCMID Global 2026) - No abstract available

Clinical • P3 data • Infectious Disease • Nephrology

New-generation antibiotics and non-antibiotic strategies against carbapenemase-producing Enterobacterales: More focus on metallo-β-lactamase producers. (PubMed, Int J Antimicrob Agents) - "Continued monitoring of resistance trends and the development of innovative therapeutic strategies is warranted in the ongoing battle against CPE harboring blaMBL."

Journal • Review • Infectious Disease

Rifamycin-, macrolide-, and ethambutol-free combinations to treat Mycobacterium avium complex lung disease. (PubMed, Int J Tuberc Lung Dis) - "OBJECTIVEPoor sustained sputum culture conversion with guidelines-based therapy for Mycobacterium avium complex lung disease highlights the need for new and improved multidrug combinations.DESIGNWe tested eight drugs by performing minimum inhibitory concentration (MIC) experiments with the ATCC#700898 strain and 49 clinical isolates, followed by single and multidrug combination studies.RESULTSMIC90 of rifabutin, rifampin, azithromycin, and ethambutol were 4, 16, 256, and 128 mg/L, respectively. The tebipenem-tedizolid-minocycline combination killed 4.82 ± 0.42 log10 CFU/mL; however, addition of bedaquiline resulted in a lower kill of 2.71 ± 0.22 log10 CFU/mL, suggesting a likely antagonism.CONCLUSIONWe tested eight different drugs to identify several rifamycin-, macrolide-, and ethambutol-free oral multidrug combinations. The minocycline-based regimens warrant further preclinical and clinical testing.."

Journal • Pulmonary Disease • Respiratory Diseases

Population Pharmacokinetic and Pharmacodynamic Prediction for Tebipenem Pivoxil Treatment of Pediatric Shigellosis. (PubMed, Clin Transl Sci) - "Three levels of ceftriaxone resistance were simulated to examine how dynamic ceftriaxone resistance may impact the trial outcome. Our findings suggest that more frequent tebipenem pivoxil dosing may increase the chance of producing treatment effects, contribute valuable insights to inform dosing strategy selection, and demonstrate a workflow that can be adapted to other drugs and diseases."

Clinical • Journal • PK/PD data • Infectious Disease • Pediatrics

Exploring the activity of a novel orally bioavailable β-lactam-β-lactamase inhibitor combination, ceftibuten-ledaborbactam, against Enterobacterales-carrying blaOXA-48. (PubMed, Microbiol Spectr) - "In this study, we compared the in vitro antimicrobial activity of ceftibuten-ledaborbactam with that of other oral antibiotics, including tebipenem, sulopenem, ceftibuten-clavulanic acid, amoxicillin-clavulanic acid, and levofloxacin, against OXA-48-producing Enterobacterales. Our results show that ceftibuten-ledaborbactam has the most potent activity, with an MIC90 of 0.5 mg/L."

Journal

Spero Announces NDA Resubmission of Tebipenem HBr by GSK to the FDA for the Treatment of Complicated Urinary Tract Infections, Including Pyelonephritis (GlobeNewswire) - "The NDA resubmission is supported by results from the successful Phase 3 PIVOT-PO trial (NCT number – NCT06059846)."

FDA filing • Infectious Disease

Carbapenem and Cephalosporin resistance in E. coli and Shigella spp. after second line treatment with Tebipenem pivoxil or Ceftriaxone for bloody diarrhoea among children in Bangladesh (ASTMH 2025) - P2 | "We enrolled 132 children, aged 24-59 months, with bloody diarrhoea after 48 hours of azithromycin therapy. Our findings suggest oral tebipenem may be a viable alternative to ceftriaxone for second-line treatment of bloody diarrhoea, particularly in the context of antimicrobial stewardship. However, further research is warranted to confirm these findings and assess long-term outcomes."

Clinical • Late-breaking abstract

Clinical efficacy of tebipenem-pivoxil versus ceftriaxone as second-line treatment for childhood shigellosis: a randomized phase IIb non-inferiority trial (ASTMH 2025) - P2 | "This single-blind, phase IIb, non-inferiority trial (NCT05121974) enrolled children aged 24-59 months with shigellosis unresponsive to azithromycin. For the primary analysis, the wide confidence interval suggests substantial uncertainty in the estimated difference, with possible values ranging from Tebipenem being slightly better than Ceftriaxone (risk difference −4.82%) to markedly worse (up to 25.68%) and the result remains inconclusive. The drug demonstrated an acceptable safety profile consistent with previous findings."

Clinical • Head-to-Head • Late-breaking abstract • P2b data

Oral β-lactam combinations are effective in vitro against Mycobacterium avium, regardless of clarithromycin susceptibility. (PubMed, Microbiol Spectr) - "Among the M. avium clinical isolates, faropenem combined with cefuroxime showed the highest synergistic effect, and amoxicillin combined with tebipenem showed the lowest minimum inhibitory concentration. In contrast, Mycobacterium intracellulare showed lower susceptibility to β-lactams. Given this difference in drug susceptibility, we emphasize the clinical need to distinguish Mycobacterium avium and Mycobacterium intracellulare to optimize treatment of Mycobacterium avium complex pulmonary disease."

Journal • Preclinical • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases