|Systematic (IUPAC) name|
(6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-ylidene)- 2-nitroso-1-oxoethyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)- 3-pyrrolidinyl]-3-pyrrolidinylidene]methyl]-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
|AHFS/Drugs.com||International Drug Names|
|ATC code||J01DI01 (WHO) |
|Molar mass||534.568 g/mol|
|(what is this?)|
Ceftobiprole (Zevtera/Mabelio) is a new 5th-generation cephalosporine for the treatment of hospital-acquired pneumonia (HAP, excluding ventilator-associated pneumonia, VAP) and community-acquired pneumonia (CAP). It is marked by Basilea Pharmaceutica in the United Kingdom, Germany, Switzerland and Austria under the trade name Zevtera, in France and Italy under the trade name Mabelio. Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for PBP2a of methicillin-resistant Staphylococcus aureus (MRSA) strains and retains its activity against strains that express divergent mecA gene homologues (mecC or mecALGA251). Ceftobiprole also binds to PBP2b in Streptococcus pneumoniae (penicillin-intermediate), to PBP2x in S. pneumoniae (penicillin resistant), and to PBP5 in Enterococcus faecalis.
Ceftobiprole has shown in vitro antimicrobial activity against a broad range of Gram-positive and Gram-negative pathogens. Among the Gram-positive pathogens, ceftobiprole has demonstrated good in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA) and coagulase-negative staphylococci, as well as against MRSA strains with reduced susceptibility to linezolid, daptomycin or vancomycin. Ceftobiprole has also displayed potent activity against Streptococcus pneumoniae (including penicillin-sensitive, penicillin-resistant and ceftriaxone-resistant strains) and Enterococcus faecalis, but not against Enterococcus faecium. For Gram-negative pathogens, ceftobiprole has shown good in vitro activity against Haemophilus influenzae (including both ampicillin-susceptible and ampicillin-non-susceptible isolates), Pseudomonas aeruginosa and strains of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis not producing extended-spectrum β-lactamase (ESBL). Like all other cephalosporines, ceftobiprole was inactive against ESBL producing strains.
The efficacy of ceftobiprole has been demonstrated in two large randomized, double-blind, phase 3 clinical trials in patients with HAP and CAP. Ceftobiprole was non-inferior to ceftazidime plus linezolid in the treatment of HAP (excluding VAP) and non-inferior to ceftriaxone with or without linezolid in the treatment of CAP.
Ceftobiprole is the active moiety of the prodrug ceftobiprole medocaril and is available for i.v. treatment only. The recommended dose is 500 mg as 2-hour infusion every 8 hours. It is mainly excreted renally. Dose adjustment is required for patients with moderate or severe renal impairment and for patients with end-stage renal disease, but no dose adjustment is needed by gender, ethnicity or age, in severely obese patients or in patients with hepatic impairment.
Ceftobiprole has been approved for the treatment of adult patients with hospital acquired pneumonia (excluding VAP) and community acquired pneumonia in 12 European countries, Canada and Switzerland.
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