A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation

Int J Antimicrob Agents. 2012 Mar;39(3):240-6. doi: 10.1016/j.ijantimicag.2011.11.005. Epub 2012 Jan 9.

Abstract

Community-acquired pneumonia (CAP) is a serious infection requiring hospitalisation in 20% of cases. The novel cephalosporin ceftobiprole has microbiological activity against the major bacterial pathogens causing CAP, including Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae, as well as against Staphylococcus aureus, including meticillin-resistant S. aureus (MRSA). This was a multicentre, double-blind study in which 706 patients with CAP severe enough to require hospitalisation were randomised to ceftobiprole or to an expert-recommended course of ceftriaxone ± linezolid (comparator group). Clinical and microbiological outcomes were determined 7-14 days after completion of therapy (test-of-cure visit). For the 469 clinically evaluable patients, cure rates were 86.6% vs. 87.4% for ceftobiprole and comparator, respectively [95% confidence interval (CI) of the difference, -6.9% to 5.3%]; in the intention-to-treat (ITT) analysis of 638 CAP patients, these cure rates were 76.4% vs. 79.3%, respectively (95% CI of the difference, -9.3% to 3.6%). A typical bacterial pathogen was identified in 29% of the ITT population. Microbiological eradication rates in the 144 microbiologically evaluable patients were 88.2% and 90.8% for the respective treatment groups (95% CI of the difference, -12.6% to 7.5%). Both study drugs were well tolerated, with but a minority of patients requiring premature discontinuation due to an adverse event (6% in the ceftobiprole group and 4% in the comparator group). The overall incidence of treatment-related adverse events was higher in the ceftobiprole group, primarily owing to differences in rates of self-limited nausea (7% vs. 2%) and vomiting (5% vs. 2%). In summary, ceftobiprole was non-inferior to the comparator (ceftriaxone ± linezolid) in all clinical and microbiological analyses conducted, suggesting that ceftobiprole has a potential role in treating hospitalised patients with CAP. [ClinicalTrials.gov identifier: NCT00326287].

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Ceftriaxone / pharmacology*
  • Cephalosporins / adverse effects
  • Cephalosporins / pharmacology*
  • Community-Acquired Infections / drug therapy*
  • Community-Acquired Infections / microbiology
  • Disease Eradication / statistics & numerical data
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Hospitalization*
  • Humans
  • Linezolid
  • Male
  • Middle Aged
  • Oxazolidinones / pharmacology*
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / microbiology
  • Treatment Outcome
  • Young Adult

Substances

  • Acetamides
  • Cephalosporins
  • Oxazolidinones
  • Ceftriaxone
  • Linezolid
  • ceftobiprole medocaril

Associated data

  • ClinicalTrials.gov/NCT00326287