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.
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].
Janssen Pharmaceuticals Scientific Affairs LLC., Titusville, NJ, USA. snicho10@its.jnj.com
Susan C
SC
Nicholson
Tobias
T
Welte
Thomas M
TM
File
Richard S
RS
Strauss
Bart
B
Michiels
Pratibha
P
Kaul
Dainius
D
Balis
Deborah
D
Arbit
Karen
K
Amsler
Gary J
GJ
Noel
D000081:Acetamides / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002443:Ceftriaxone / Q000494:pharmacology*; D002511:Cephalosporins / Q000009:adverse effects / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D060740:Disease Eradication / Q000706:statistics & numerical data; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000494:pharmacology*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D055815:Young Adult
D000081:Acetamides; D002511:Cephalosporins; D023303:Oxazolidinones; D002443:Ceftriaxone; D000069349:Linezolid; C505439:ceftobiprole medocaril