title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Royal Hampshire County Hospital, Winchester SO22 5DG, UK matthew.dryden@hhft.nhs.uk.
authors: Matthew
authors: M
authors: Dryden
authors: Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Zhong Road, Shanghai 200040, P.R. China.
authors: Yingyuan
authors: Y
authors: Zhang
authors: AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK.
authors: David
authors: D
authors: Wilson
authors: AstraZeneca, 35 Gatehouse Drive, Waltham, MA, USA.
authors: Joseph P
authors: JP
authors: Iaconis
authors: AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK.
authors: Jesus
authors: J
authors: Gonzalez
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001398:Aztreonam / Q000008:administration & dosage* / Q000009:adverse effects; D002511:Cephalosporins / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017192:Skin Diseases, Bacterial / Q000150:complications / Q000188:drug therapy*; D018461:Soft Tissue Infections / Q000150:complications / Q000188:drug therapy*; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D001398:Aztreonam; D002511:Cephalosporins; D014640:Vancomycin; D000097583:Ceftaroline