title: Pharmacokinetic and pharmacodynamics evaluation of ceftobiprole medocaril for the treatment of hospital-acquired pneumonia.
abstract: BACKGROUND
  Ceftobiprole is a cephalosporin with activity against methicillin-resistant Staphylococcus aureus, Enterobacteriaceae, and Pseudomonas aeruginosa with a promising role in the treatment of hospital-acquired pneumonia (HAP). Cure rates, however, with ceftobiprole at the doses studied may be inferior to conventional treatment in the ventilator-acquired subset of HAP.
  
  
  METHODS
  Literature was sought using PubMed and through abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy (2006 - 2012) and the European Congress of Clinical Microbiology and Infectious Diseases (2007 - 2012). The authors used the search terms "ceftobiprole," "BAL9141," "RO63-9141," "BAL5788," and 'RO5788." The article discusses the activity, mechanism of action, pharmacokinetics (PK), pharmacodynamics (PD), and clinical trials of ceftobiprole in HAP. The article also provides discussion of how PK/PD parameters play a role in the outcome of HAP treatment and how dosing in ventilator-associated pneumonia (VAP) should be reconsidered in light of altered PK/PD.
  
  
  CONCLUSIONS
  In patients with normal PK and non-VAP, ceftobiprole is effective for the treatment of HAP in the recommended doses, ceftobiprole is unlikely to achieve the desired PD targets when PK parameters are altered in VAP (e.g., increased volume of distribution and clearance). In these settings, off-label use at higher doses may overcome these limitations; but in the presence of alternative therapies, it cannot be currently recommended.
authors.affiliation: St. Boniface General Hospital/Diagnostic Services of Manitoba, Department of Microbiology, Winnipeg, Manitoba, R2H 2A6, Canada. plagacewiens@dsmanitoba.ca
authors.forename: Philippe R S
authors.initials: PR
authors.lastname: Lagacé-Wiens
authors.forename: Ethan
authors.initials: E
authors.lastname: Rubinstein
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C505439:ceftobiprole medocaril