title: Ceftobiprole: a novel cephalosporin with activity against Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus (MRSA).
abstract: Ceftobiprole is a novel broad-spectrum cephalosporin with activity against a wide range of Gram-positive and Gram-negative bacteria, including several resistant species such as methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. Ceftobiprole is administered intravenously as the prodrug ceftobiprole medocaril, which is almost immediately converted to the active form. It is currently under review by the US Food and Drug Administration (FDA) and is approved in Canada under the trade name Zeftera. The pharmacokinetics of ceftobiprole are non-complex as it displays a two-compartment model, dose proportionality, linear plasma protein binding and negligible accumulation. The volume of distribution is approximately equal to the extracellular fluid volume and it is cleared primarily by glomerular filtration, resulting in a half-life of approximately 3-4h. Ceftobiprole displays a low plasma protein binding of approximately 22%. The efficacy of ceftobiprole was demonstrated in two pivotal studies in patients with complicated skin and skin-structure infections (cSSSIs) that compared ceftobiprole with vancomycin in Gram-positive infections in one study and ceftobiprole with vancomycin plus ceftazidime in Gram-positive and Gram-negative infections in the other. The clinical cure rates were similar for ceftobiprole vs. comparator treatments: 93.3% vs. 93.5% with vancomycin only and 90.5% vs. 90.2% with vancomycin plus ceftazidime. The pharmacokinetic/pharmacodynamic profile supports the use of ceftobiprole to treat a wide range of cSSSIs.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: April
authors.initials: A
authors.lastname: Barbour
authors.forename: Stephan
authors.initials: S
authors.lastname: Schmidt
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Rand
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002170:Canada; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D016896:Treatment Outcome; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C443755:ceftobiprole