IDStewardship

Tebipenem (Utebzi)

KEY POINTS

  • Tebipenem pivoxil (Utebzi) is pro-drug, penem, and beta-lactam antibiotic. The active form is tebipenem and it is a carbapenem.
    • Tebipenem is the second antibiotic approved from this class, after sulopenem which has utility for cystitis (lower UTI).
      • Administered as tebipenem pivoxil (a prodrug) that is converted to the active form tebipenem upon oral administration. As a beta-lactam it is a time-dependent killer. Adequate concentrations must be achieved at the site of infection for a long enough time during the dosing interval to achieve clinical efficacy.
      • The bactericidal action of tebipenem is mediated through binding to penicillin-binding proteins (PBPs), including 1a, 1b, 2, 3, 4 and 5/6 with preferential binding to PBP 2. This leads to bacterial cell wall inhibition.
  • FDA-approved 17 June 2026 for the treatment of adults with complicated urinary tract infections, including pyelonephritis. Has been approved in Japan since 2009, under the brand name Orapenem.
    • Has utility for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae species complex, Klebsiella oxytoca, and Enterococcus faecalis
    • Can be used to treat ESBL-producing bacteria, including some producers of TEM, SHV, CTX-M, oxacillinases, and AmpC
    • May have activity but clinical significance is unknown for: Citrobacter freundii complex, Citrobacter koseri, Klebsiella aerogenes, Morganella morganii, Proteus mirabilis, Providencia rettgeri, Klebsiella variicola, Serratia marcescens, Staphylococcus aureus, Staphylococcus saprophyticus, and Streptococcus agalactiae
    • Is not active against serine carbapenemases (e.g., KPC, OXA-48) or metallo-carbapenemases (e.g., NDM, VIM)
    • Does not have utility for Pseudomonas aeruginosa
    • The package insert does not list extrapolating susceptibility from other carbapenems
  • Dosed as 600 mg (two tablets) PO Q6H for 7-10 days
    • Requires dose/frequency adjustment for kidney function when eGFR is below 60 mL/min and tebipenem is removed by hemodialysis
    • Use is not recommended when eGFT is above 150 mL/min due to reduced tebipenem exposure
    • Does not undergo hepatic metabolism, no dose adjustment recommended in hepatic dysfunction
    • Can be taken with or without food
  • Listed to be contraindicated in patients “with hypersensitivity to other beta-lactam antibiotics”, but what that means in practice is unclear given the variety of antibiotics that are beta-lactams and the spectrum of what can be considered a hypersensitivity reaction
  • Listed as contraindicated in patients with primary or secondary carnitine deficiency or inborn errors of metabolism that may result in clinically significant carnitine deficiency
  • Warnings include:
    • Hypersensitivity reactions
    • Seizures and other central nervous system reactions
    • Use with valproic acid or divalproex sodium can lead to reduced concentrations of these medications and potentially cause a seizure
    • Secondary carnitine deficiency may occur
    • Clostridium difficile infection
    • Interference with Newborn Screening Test – can cause a false positive test for isovaleric acidemia in the newborn screening. Prompt follow-up of a positive newborn screening result for isovaleric acidemia is recommended
  • The most common side effects are diarrhea, headache, nausea, abdominal pain, hepatic enzyme increased, and C. difficile infection
  • Has drug-drug interactions with inhibitors of OAT1 and OAT3 (e.g., probenecid), which can increase tebipenem concentrations
  • In the clinical trial tebipenem was compared to imipenem-cilastatin, where it was found to have a similar clinical cure and microbiological response
    • In a subgroup of patients with concomitant bacteremia, test of cure was about 21% higher in the imipenem-cilastatin group
  • Provided in a blister pack of 80 tablets, with 8 tablets per blister strip
  • Can be stored 20°C to 25°C (68°F to 77°F)
  • Manufactured for GlaxoSmithKline (GSK)
  • A major concern with tebipenem is that over-use could contribute to increased carbapenem resistance
  • A major benefit of tebipenem is that it may help avoid hospitalizations, reduce hospital length of stay, and avoid use of venous catheters in patients with drug-resistant bacterial infections that otherwise only have intravenous options
  • As of June 2026 is not available for purchase in the United States. Is expected to be expensive as a new brand-online medicine.

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