Ceftobiprole medocaril (Zevtera)

Ceftobiprole medocaril (Zevtera) picture sourced from mims.co.uk

KEY POINTS

• Ceftobiprole (Zevtera, Mabelio) is a cephalosporin antibiotic that works by interfering with bacterial cell wall synthesis (binds to penicillin binding proteins [PBPs]), exhibits time-dependent killing activity
  • Ceftobiprole medocaril is a prodrug of the active moiety ceftobiprole
  • Ceftobiprole exhibits linear and time-dependent pharmacokinetics
• There was great enthusiasm for ceftobiprole in ~2008 from J&J, but the FDA did not approve it. This letter was released by J&J in 2009 when it was rejected by FDA. It would have been the first anti-MRSA cephalosporin to hit the market, instead ceftaroline (approved in 2010).
• Ceftobiprole was FDA approved on April 3, 2024 (provided by Basilea Pharma) for the treatment of adults with:
  1. Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis
     • In adults dosed as 667 mg IV every 6 hours on day 1-8, then 667 mg IV every 8 hours from day 9 on, treated up to 42 days
     • Ceftobiprole has demonstrated non-inferiority to daptomycin for treatment of complicated Staph. aureus bacteremia
  2. Adults with acute bacterial skin and skin structure infections (ABSSSI)
     • In adults dosed as 667 mg IV every 8 hours treated up to 5-14 days
  3. Adult and pediatric patients three months to less than 18 years old with community-acquired bacterial pneumonia (CABP)
     • In adults dosed as 667 mg IV every 8 hours treated up to 5-14 days
• Dose adjust in adults:
  • Daily dose must be adjusted down when CrCl is below 50 mL/min
  • Daily dose must be adjusted up when CrCl is 150 mL/min or more
• Ceftobiprole is administered IV over 2 hours
• Supplied as a carton of 10 vials. Vials are stored under refrigerated. The drug is a white, yellowish to brown powder, with each vial containing 667 mg of ceftobiprole medocaril sodium
  • Each vial has an equivalent of 500 mg of ceftobiprole
• Ceftobiprole broad spectrum anti-bacterial activity, including coverage for:
  • Staphylococcus aureus (including MRSA)
    • Ceftobiprole has high affinity to PBP2a, giving it MRSA activity
  • Streptococcus pyogenes
  • Streptococcus pneumonia
    • Ceftobiprole has high affinity for PBP2x & PBP2b, giving it activity against penicillin-resistant isolates
  • Haemophilus influenzae & H. parainfluenzae
  • E. coli
  • Klebsiella pneumoniae
  • Not active against ESBL-producing gram negatives (CTX-M, TEM, SHV)
  • Not active against serine beta-lactamases (e.g., KPC which is Ambler class A), Ambler class B enzymes, Ambler class C enzymes, or Ambler class D enzymes
• Holds warnings for:
  • Increased mortality if used for ventilator associated bacterial pneumonia (VABP)
  • Hypersensitivity reactions
  • Seizsures and other CNS effects
  • Diarrhea, including C. difficile infection
• Side effects include nausea, anemia, hypokalemia, vomiting, hepatic enzyme elevation, and others listed in the package inset
• May increase concentrations of OATP1B1 and OATP1B3 substrates
• Should not be co-administered simultaneously or mixed with calcium-containing products
• Use can result in false-positive dipstick results (urine protein, ketones, occult blood)

RESOURCES

• Ceftobiprole medocaril (Zevtera) Package Insert
• Ceftobiprole medocaril (Zevtera) prescribing information from Avir Pharma (Canada)
• Ceftobiprole Medocaril Sodium for Injection FDA Breakpoints Page
• Ceftobiprole FDA approval news release (April 2024)
• Basilea announces FDA acceptance of New Drug Application for antibiotic ceftobiprole
• Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia
• Ceftobiprole Perspective: Current and Potential Future Indications
• FDA Issues Complete Response Letter for Ceftobiprole for Treatment of Complicated Skin Infections

MEMES

Memes of ID experts hearing ceftobiprole was finally FDA-approved…