Ceftobiprole (Zevtera/Mabelio) is a fifth-generation cephalosporin for the treatment of

hospital-acquired pneumonia Hospital-acquired pneumonia (HAP) or nosocomial pneumonia refers to any pneumonia contracted by a patient in a hospital at least 48–72 hours after being admitted. It is thus distinguished from community-acquired pneumonia. It is usually caused by ...

(excluding ventilator-associated pneumonia) and

community-acquired pneumonia Community-acquired pneumonia (CAP) refers to pneumonia (any of several lung diseases) contracted by a person outside of the healthcare system. In contrast, hospital-acquired pneumonia (HAP) is seen in patients who have recently visited a hospital ...

. It is marketed 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 penicillin-binding protein 2a of methicillin-resistant ''Staphylococcus aureus'' strains and retains its activity against strains that express divergent mecA gene homologues (mecC or mecALGA251). Ceftobiprole also binds to penicillin-binding protein 2b in ''

Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They ar ...

'' (penicillin-intermediate), to penicillin-binding protein 2x in ''Streptococcus pneumoniae'' (penicillin-resistant), and to penicillin-binding protein 5 in ''

Enterococcus faecalis ''Enterococcus faecalis'' – formerly classified as part of the group D ''Streptococcus'' system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans. Like other species in the genus ''Enterococcus'', ''E ...

''.

Microbiology

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'', methicillin-susceptible ''Staphylococcus aureus'' and coagulase-negative ''staphylococci'', as well as against strains of methicillin-resistant ''Staphylococcus aureus'' 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 ''Enterococcus faecium'' is a Gram-positive, gamma-hemolytic or non- hemolytic bacterium in the genus ''Enterococcus''. It can be commensal (innocuous, coexisting organism) in the gastrointestinal tract of humans and animals, but it may also be ...

''. For Gram-negative pathogens, ceftobiprole has shown good in vitro activity against ''

Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacter ...

'' (including both ampicillin-susceptible and ampicillin-non-susceptible isolates), ''Pseudomonas aeruginosa'' and strains of ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

Klebsiella pneumoniae ''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar. Although found in the normal flora of the mo ...

and

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus'' infections in humans. It is widely distributed in soil and ...

'' that do not produce extended-spectrum β-lactamases ( ESBL). Like all other cephalosporins, ceftobiprole was inactive against strains that produce extended-spectrum β-lactamases. The efficacy of ceftobiprole has been demonstrated in two large randomized, double-blind, phase 3 clinical trials in patients with hospital-acquired and community-acquired pneumonia. Ceftobiprole was non-inferior to ceftazidime plus linezolid in the treatment of hospital-acquired pneumonia (excluding ventilator-acquired pneumonia) and non-inferior to ceftriaxone with or without linezolid in the treatment of community-acquired pneumonia.

Pharmacology

Ceftobiprole is the active moiety of the prodrug ceftobiprole medocaril and is available for intravenous 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 Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

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.

Regulatory approvals

Ceftobiprole has been approved for the treatment of adult patients with hospital acquired pneumonia (excluding ventilator-acquired pneumonia) and community-acquired pneumonia in 12 European countries, Canada and Switzerland.

Synonyms

*RO0639141-000 *BAL9141 *Ceftobiprole medocaril

References

External links

* {{Portal bar , Medicine Cephalosporin antibiotics Thiadiazoles Ketoximes Pyrrolidines Pyrrolidones