title: Results of a double-blind, randomized trial of ceftobiprole treatment of complicated skin and skin structure infections caused by gram-positive bacteria.
abstract: Ceftobiprole is the first broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) to be assessed in late-stage clinical trials. As a pivotal step in the clinical development of ceftobiprole, a multicenter, global, randomized, double-blind trial was conducted to compare the efficacy of ceftobiprole to that of vancomycin in patients with complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. The primary objective was to assess noninferiority on the basis of the cure rates 7 to 14 days after the completion of therapy in patients administered ceftobiprole 500 mg every 12 h or vancomycin 1 g every 12 h. Of 784 patients randomized, 282 receiving ceftobiprole and 277 receiving vancomycin were clinically evaluable. Of these patients, 93.3% treated with ceftobiprole and 93.5% treated with vancomycin were cured (95% confidence interval of difference, -4.4%, 3.9%). The cure rates for patients with MRSA infections were 91.8% (56/61) with ceftobiprole treatment and 90.0% (54/60) with vancomycin treatment (95% confidence interval of difference, -8.4%, 12.1%). At least one adverse event (AE) was reported by 52% of the ceftobiprole-treated patients and 51% of the vancomycin-treated patients. The most common AEs reported by the ceftobiprole-treated patients were nausea (14%) and taste disturbance (8%). Discontinuation of the study drug because of treatment-emergent AEs occurred in 4% (n = 17) of the ceftobiprole-treated patients and 6% (n = 22) of the vancomycin-treated patients. The results of this trial support the use of ceftobiprole as an effective and well-tolerated treatment option for patients with cSSSIs caused by a spectrum of gram-positive bacteria.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, LLC, 900 Route 202, Raritan, NJ 08869, USA. GNoel1@prdus.jnj.com
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Noel
authors.forename: Richard S
authors.initials: RS
authors.lastname: Strauss
authors.forename: Karen
authors.initials: K
authors.lastname: Amsler
authors.forename: Markus
authors.initials: M
authors.lastname: Heep
authors.forename: Rienk
authors.initials: R
authors.lastname: Pypstra
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Solomkin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002511:Cephalosporins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006095:Gram-Positive Cocci / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D014640:Vancomycin; C505439:ceftobiprole medocaril