IDStewardship

Cefepime-enmetazobactam (Exblifep)

Cefepime-enmetazobactam (Exblifep) photo pending

KEY POINTS

  • Cefepime-enmetazobactam (Exblifep) was FDA-approved on 22 February 2024 for treatment of adult patients with complicated urinary tract infection including pyelonephritis caused by designated susceptible organisms
    • The FDA approval includes that it should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria
    • Is approved in Europe for UTI and pneumonia
    • Cefepime is a fourth-generation cephalosporin and beta-lactam antibiotic that inhibits bacterial cell wall synthesis
    • Enmetazobactam is a beta-lactamase inhibitor which is effective versus serine beta-lactamases such as extended-spectrum beta-lactamases (ESBL)
    • Cefepime-enmetazobactam is essentially a drug for ESBL-producing Gram negatives, as it has demonstrated activity against organisms that produce CTX-M, SHV, TEM, and VEB.
      • Target bacteria include: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex
    • Cefepime-enmetazobactam does not have activity against KPC, metallo-beta-lactamases, or some oxacillinases
  • Usual dose is 2.5 grams diluted in 250 mL of D5W or NS given IV every 8 hours, each dose administered over 2 hours
    • Recommended to give via a 4-hour infusion if eGFR is 130 or more
    • Requires renal dose adjustment for eGFR below 90
  • Has warnings for hypersensitivity reaction, neurotoxicity (has been seen with cefepime), and C. difficile associated diarrhea.
    • Care should be taken to ensure appropriate doses are given to elderly patients, to reduce neurotoxicity risk
  • Adverse effects may include increased transaminase, increased bilirubin, headache, and phlebitis/ infusion site reaction
  • Supplied in packs of 10 vials, each with 2.5 grams (2 grams cefepime + 0.5 grams enmetazobactam)
    • Vials require refrigeration
    • IV administration of the diluted solution is to be completed within 6 hours of dilution
  • In a study for complicated UTI or acute pyelonephritis caused by gram-negative pathogens, cefepime/enmetazobactam, compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication.

PLACE IN THERAPY

So when will cefepime-enmetazobactam (Exblifep) be used?

I’m not exactly sure. This drug wasn’t really even on my radar until I saw the approval. It can work for ESBLs but it’s IV only. It will likely be cost-prohibitive upon entering the market, especially when a day of meropenem or ertapenem is well below $50 for the drug acquisition cost. Based on other newer beta-lactam drugs to enter the market, I’m expecting cefepime-enmetazobactam to routinely cost ballpark $750-$1500 per day. It does not have much outpatient appeal as it seems to have some stability challenges, not to mention every 8 hour dosing for many patients (depends on renal function). Susceptibility testing is unlikely to be readily available.

So out of the gate, I don’t see a lot of use. It’s great to have more options though. Where do you see it being used? Tag @IDstewardship on X and let me know!

  • Will the superiority data be enough to influence use? This is a question that should be debated.

Here is a fantastic resource from the Society of Infectious Diseases Pharmacists to help put things in perspective more:

RESOURCES

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