Pharmacokinetic and pharmacodynamics evaluation of ceftobiprole medocaril for the treatment of hospital-acquired pneumonia

Introduction: 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. Areas covered: 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. Expert opinion: 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.