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

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 21.0%, 95% CI 26.9, 5.4) and 342/395 (86.6%) versus 180/211 (85.3%) patients (difference 1.3%, 95% CI24.3, 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.