A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities

J Antimicrob Chemother. 2016 Dec;71(12):3575-3584. doi: 10.1093/jac/dkw333. Epub 2016 Sep 1.

Abstract

Objectives: Increasing the ceftaroline fosamil dose beyond 600 mg every 12 h may provide additional benefit for patients with complicated skin and soft tissue infections (cSSTIs) with severe inflammation and/or reduced pathogen susceptibility. A Phase III multicentre, randomized trial evaluated the safety and efficacy of ceftaroline fosamil 600 mg every 8 h in this setting.

Methods: Adult patients with cSSTI and systemic inflammation or comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g every 8 h) for 5-14 days. Clinical cure was assessed at the test of cure (TOC) visit (8-15 days after the final dose) in the modified ITT (MITT) and clinically evaluable (CE) populations. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference greater than -10%. An MRSA-focused expansion period was initiated after completion of the main study. Clinicaltrials.gov registration numbers NCT01499277 and NCT02202135.

Results: Clinical cure rates at TOC demonstrated non-inferiority of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in the MITT and CE populations: 396/506 (78.3%) versus 202/255 (79.2%) patients (difference -1.0%, 95% CI -6.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI -4.3, 7.5), respectively. In the expansion period, 3/4 (75%) patients treated with ceftaroline fosamil were cured at TOC. The frequency of adverse events was similar between groups.

Conclusions: Ceftaroline fosamil 600 mg every 8 h was effective for cSSTI patients with evidence of systemic inflammation and/or comorbidities. No new safety signals were identified.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Aztreonam / administration & dosage*
  • Aztreonam / adverse effects
  • Cephalosporins / administration & dosage*
  • Cephalosporins / adverse effects
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Skin Diseases, Bacterial / complications
  • Skin Diseases, Bacterial / drug therapy*
  • Soft Tissue Infections / complications
  • Soft Tissue Infections / drug therapy*
  • Systemic Inflammatory Response Syndrome / drug therapy*
  • Treatment Outcome
  • Vancomycin / administration & dosage*
  • Vancomycin / adverse effects
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Vancomycin
  • ceftaroline fosamil
  • Aztreonam

Associated data

  • ClinicalTrials.gov/NCT01499277
  • ClinicalTrials.gov/NCT02202135