Ceftobiprole: An Extended-Spectrum Anti–Methicillin-Resistant Staphylococcus aureus Cephalosporin

Shawn D Anderson, PharmD; John G Gums, PharmD, FCCP


The Annals of Pharmacotherapy. 2008;42(6):806-816. 

In This Article

Abstract and Introduction


Objective: To summarize and evaluate the literature concerning ceftobiprole.
Data Sources: Literature identification was conducted through MEDLINE (1966–February 2008) and International Pharmaceutical Abstracts (1970–February 2008) using the terms ceftobiprole, medocaril, BAL 5788, RO-5788, BAL 9141, RO 63-9141, pyrrolidinone cephalosporin, MRSA, complicated skin and skin-structure infections (cSSSIs), community-acquired pneumonia, and nosocomial pneumonia. Additional publications were identified through a review of articles and abstracts from infectious disease meetings.
Study Selection and Data Extraction: All articles in English were evaluated and all pertinent information was included.
Data Synthesis: Ceftobiprole medocaril is an extended-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus spp., vancomycin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Enterobacteriaceae, and Pseudomonas aeruginosa. Inactivity includes extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae and Enterococcus faecium. Preliminary data suggest that ceftobiprole may be effective with a 1-hour infusion of 500mg every 12 hours for gram-positive infections and 500mg every 8 hours with a 2-hour infusion for polymicrobial infections. Two clinical trials support these dosing regimens for cSSSIs. Ceftobiprole was noninferior to vancomycin in suspected gram-positive cSSSIs, with cure rates of 93.3% and 93.5%, respectively. Furthermore, ceftobiprole was noninferior to vancomycin and ceftazidime in polymicrobial cSSSIs (cure rates 90.5% vs 90.2%, respectively). Although the total number of adverse effects was similar to those of the comparator, more patients in the ceftobiprole group experienced nausea, vomiting, and dysgeusia.
Conclusions: The activity of ceftobiprole and limited clinical data suggest that it may be useful as empiric monotherapy for cSSSI and in combination with other antimicrobials in lower respiratory tract infections for which Phase 3 clinical trials are currently exploring. Although not shown in vitro, ceftobiprole may induce resistance due to its broad spectrum of activity. Approval is expected for the treatment of cSSSI.


The emergence of antimicrobial resistance is a worldwide concern. Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals and is now emerging in the community.[1,2] It is imperative that novel antibiotics be developed to overcome current resistance mechanisms. Ceftobiprole, an antimicrobial currently in development, may help fill this void and add another weapon in the war against resistant bacterial infections. Ceftobiprole medocaril (BAL 5788, RO-5788) is a water-soluble prodrug of ceftobiprole (BAL 9141, RO 63-9141) in development with Basilea Pharmaceutica and Johnson & Johnson. Ceftobiprole is a pyrrolidinone cephalosporin that has a broad spectrum of activity against gram-positive, gram-negative, and anaerobic organisms, with unique activity as a cephalosporin against methicillin-resistant and vancomycin-resistant staphylococci.[3,4] The antibiotic is currently undergoing Phase 3 clinical trials for hospital-acquired pneumonia, community-acquired pneumonia requiring hospitalization, and fever and neutropenia in patients receiving chemotherapy. Two Phase 3 clinical trials have been completed for the treatment of complicated skin and skin-structure infections (cSSSI), and an approvable letter was issued by the Food and Drug Administration (FDA) on March 18, 2007, for the treatment of cSSSI. This article reviews and evaluates ceftobiprole's mechanism of action, in vitro activity, pharmacokinetic and pharmacodynamic parameters, efficacy in clinical trials, adverse effects, and potential clinical utilization.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.