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| |  Ceftaroline Noninferior to Vancomycin Plus Aztreonam for Complicated Skin and Skin Structure Infections: Presented at ECCMID By Chris Berrie HELSINKI, Finland -- May 22, 2009 -- As a monotherapy, ceftaroline (CFT) is well tolerated and provides high clinical cure and microbiological success rates that are noninferior to vancomycin plus aztreonam (VAN/AZTR) combination therapy for patients with complicated skin and skin structure infection (cSSSI), according to researchers here at the 19th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Tanya Baculik, MD, Cerexa, Inc., Oakland, California, presented this multicentre, randomised, double-blind comparative study on May 18. Although cSSSI are mainly caused by Gram-positive pathogens, various Gram-negative bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), are becoming increasingly prevalent causes of cSSSI. The researchers aimed to establish the noninferiority of CFT versus VAN/AZTR for treatment of patients with cSSSI. Also, as Dr. Baculik noted, "The aztreonam has to be there to cover the flora that VAN does not, to match the potential of CFT, to have equal comparators, with the same spectrum of coverage." The study included adults with local and systemic evidence of cSSSI, with 694 patients randomised to receive CFT 600 mg intravenously (IV) every 12 hours or VAN 1 g IV plus AZTR 1 g IV every 12 hours for 5 to 14 days. AZTR was discontinued if no Gram-negative pathogen was suspected or identified. The primary outcome was noninferiority for clinical cure rate of CFT versus VAN/AZTR at the test-of-cure (TOC) visit for the modified intention-to-treat (mITT) patient population (all patients who received any study drug). Further outcome measures included microbiological eradication at TOC and safety evaluation. Baseline clinical characteristics of the mITT population for the 342 CFT patients (mean age, 47.8 years; male, 65.5%) and 338 VAN/AZTR patients (mean age, 47.5 years; male, 59.5%) were similar and included polymicrobial infection (23.1% for CFT vs 19.8% for VAN/AZTR), bacteraemia (2.6% vs 4.1%), recent trauma (32.2% vs 27.8%), diabetes (17.5% vs 15.4%), peripheral vascular disease (13.5% vs 11.8%), and relevant surgical procedure (10.8% vs 13.0%). The infection types in the study population were deep/extensive cellulitis (30.1% vs 36.4%), major abscess (40.6% vs 39.3%), wound (14.0% vs 11.5%), burn (0.3% vs 0.6%), ulcer (9.1% vs 6.2%), lower extremity (diabetes/peripheral vascular disease; 2.6% vs, 3.6%), bite (1.8% vs, 1.2%), and other (1.5% vs, 1.2%). The clinical cure rates for the mITT population at TOC were similar between the CFT and VAN/AZTR treatment groups, at 85.1% and 85.5%, respectively. These rates remained between 75% and 100% for both treatments. The microbiological response rates were also similar, at 86.6% and 88.4%. Clinical cure rates varied according to pathogens isolated, the most common being S aureus. Both treatment groups showed clinical cure rates that exceeded 90% for MRSA and methicillin-susceptible S aureus. In the safety analysis, most averse events were mild and judged to be unrelated to treatment, with similar levels seen across the treatment groups. The most common adverse events for CFT treatment were diarrhoea (6.5%), nausea (6.2%), and headache (5.3). Adverse events for VAN/AZTR treatment included pruritus (8.3%), nausea (85.6%), and headache (5.3%). Dr. Baculik concluded, "CFT has the potential to be the monotherapy for the typical skin infections, and not only Gram positives, but also some Gram negatives [are covered] very nicely." Funding for this study was provided by Cerexa, a subsidiary of Forest Laboratories, Inc. [Presentation title: CANVAS-2: Randomized, Double-Blinded, Phase 3 Study (P903-07) of the Efficacy and Safety of Ceftaroline vs Vancomycin Plus Aztreonam in Complicated Skin and Skin-Structure Infections. Abstract P1792]
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