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Cefepime-zidebactam (Zaynich)

Cefepime-zidebactam (Zaynich) photo pending

Top Clinical Considerations

  1. Approved for use in treating UTI including pyelonephritis and was studied in patients that also had secondary bacteremia
  2. Has potential to be used for Gram negative bacteria with a variety of drug resistance mechanisms, as a carbapenem-sparing agent
  3. Intravenous only and inconveniently dosed for most patients every 8 hours, adjust doses/frequency for renal function

Key Points

  • Cefepime-zidebactam (Zaynich) was first FDA-approved on May 29th, 2026 for the treatment of adult patients with complicated urinary tract infection including pyelonephritis
  • Cefepime is a fourth-generation cephalosporin and beta-lactam antibiotic that inhibits bacterial cell wall synthesis. It has been used in practice for many years.
    • Cefepime-enmatazobactam (Exblifep) is also FDA approved
    • Cefepime-taniborbactam is not yet FDA approved, but may be approved soon
    • Cefepime alone primary targets penicillin binding protein 3 (PBP3)
    • Cefepime has activity against a variety of Gram positive and Gram negative bacteria, including methicillin-susceptible Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa
  • Zidebactam is a non-beta-lactam beta-lactamase inhibitor. It is less susceptible to degredation from beta-lactamases than some other beta-lactamase inhibitors. This is the first time zidebactam has been approved for use by the FDA.
    • Zidebactam primarily inhibits PBP2
    • Zidebactam inhibits Ambler Class A (e.g., SHV, TEM, CTX-M, KPC) and Class C (e.g., CMY) beta-lactamases
    • Zidebactam demonstrates activity in vitro against Entarobacterales and Pseudomonas aeruginosa
    • Cefepime-zidebactam synergistically inhibit multiple PBPs when combined together
      • This synergy occurs in the presence of beta-lactamases, including metallo-beta-lactamases, which are not inhibited by zidebactam, and non-enzymatic cefepime resistance mechanisms such as hyper-efflux and down regulation of outer membrane porin channels. This is hypothesized to be due to cefepime’s ability to bind to its PBP targets at a faster rate than it is hydrolyzed by beta-lactamases.
      • Cefepime-zidebactam has demonstrated in vitro activity against gram negatives that produce enzymes in Ambler class A, B, C, and D
      • Zidebactam can restore activity of cefepime against cefepime-resistant Enterobacterales, including isolates genetically confirmed to harbor metallo-beta-lactamases (e.g., NDM, VIM, IMP), KPC, and OXA-48-like carbapenemases.
      • Cefepime-zidebactam has activity against Pseudomonas aeruginosa with OprD loss (efflux over-expression) and those harboring carbapenemase genes such as NDM
  • Cefepime-zidebactam is IV only, doses as 3 gm (2 gm cefepime + 1 gm zidebactam), given every 8 hours over a 1-hour infusion, for 7-10 days
  • Requires dose and/or frequency adjustment for renal impairment once eGFR is below 60 mL/min
  • Has warnings for hypersensitivity reaction, neurotoxicity (has been seen with cefepime), and C. difficile associated diarrhea.
    • Neurotoxicity risk due to cefepime is greatest for patients with renal impairment when a dose adjustment is not made. Care should be taken to ensure appropriate doses are given to elderly patients.
  • The most common side effects include diarrhea, headache, hypertension, and hypokalemia
  • Supplied as a dry powder, single dose vial for reconstitution with NS, D5W, or LR
  • To be added to a 100mL infusion bag to be administered over 1 hour
  • Must be infused w/in 12 hours once final dilution, 24 hours under refrigeration
  • Was evaluated against meropenem for cUTI including pyelonephritis in patients with and without bacteremia. Clinical cure was similar for both groups (97% vs 95%, respectively) but microbiological response was better for cefepime-zidebactam (91% vs 71%, respectively).
    • The majority of infections were caused by E. coli, while a few were caused by Pseudomonas
    • Infection due to E. coli, Klebsiella pneumoniae, or Proteus mirabilis that was ESBL-producing had a higher composite outcome when cefepime-zidebactam was used (89% vs 70%, respectively)
  • Manufactured by ACS Dobfar S.p.A. for Wockhardt Suisse USA LLC

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

Resources

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