Impact of Comorbidities on the Efficacy of Ceftaroline Fosamil in Complicated Skin and Soft Tissue Infections − Pooled Analysis of 3 Studies

Treatment of cSSTI

Treatment of cSSTI includes surgical debridement/drainage and antibiotic therapy. The presence of comorbidities can affect the response of cSSTI to treatment, necessitated care, length of hospitalization, and patient mortality. These comorbidities include liver and kidney diseases, peripheral atherosclerosis, malignancies, or diabetes mellitus. Risk factors also include immunocompromised status, advanced age, and obesity. Some patients with cSSTI, regardless of comorbidities, initially require empirical antibiotic therapy with polymicrobial coverage. Ceftaroline fosamil is characterized by a broad spectrum of efficacy against clinically relevant gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA), and some gram-negative pathogens involved in the development of cSSTI.

Analyzed Studies

The multicenter randomized double-blind studies CANVAS 1, CANVAS 2, and COVERS compared the efficacy and safety of treatment with ceftaroline fosamil and the combination of vancomycin + aztreonam. They included patients with cSSTI who required hospitalization and ≥ 5 days of parenteral antibiotic therapy. In all studies, patients were randomized to receive ceftaroline fosamil or vancomycin + aztreonam for 5–14 days.

In the CANVAS 1 and 2 studies, ceftaroline fosamil (administered at a dose of 600 mg every 12 hours in a 1-hour i.v. infusion) demonstrated non-inferiority compared to vancomycin + aztreonam (administered at a dose of 1 g every 12 hours) in terms of therapeutic response at the test-of-cure visit, which took place 8–15 days after the last dose (TOC).

In the COVERS study, which included patients with extensive skin involvement, including those with signs of systemic inflammation and comorbidities associated with decreased immune response, similar results were observed with ceftaroline fosamil (administered at a dose of 600 mg every 8 hours in a 2-hour i.v. infusion) compared to vancomycin + aztreonam (administered at a dose of 5 mg/kg every 12 hours + 1 g every 8 hours).

Pooled Analysis of Comorbidities and Results

The pooled analysis of the results of these 3 studies evaluated the impact of baseline comorbidities on the primary endpoint (the proportion of therapeutic responses at TOC). The clinically evaluable population (CE) included 1808 patients (1005 with ceftaroline fosamil and 803 with vancomycin + aztreonam), with subgroups divided by age (≤ 65 years or > 65 years), presence/absence of obesity, diabetes, peripheral atherosclerosis, malignancy, and renal insufficiency.

The proportion of patients with a clinical response to treatment at TOC was 89.7% in the ceftaroline fosamil group and 90.8% in the vancomycin + aztreonam group (difference −1.13; 95% confidence interval [CI] −3.87 to 1.67). This proportion was comparable between the therapeutic groups regardless of age, presence of obesity, and individual comorbidities. Within the individual subgroups, the efficacy and safety of the treatment did not differ from the overall population. 

Adverse events were reported in 45.2% of patients treated with ceftaroline fosamil and 47.0% of those treated with vancomycin + aztreonam.

This pooled analysis demonstrated the efficacy and favorable safety profile of ceftaroline fosamil comparable to the combination of vancomycin + aztreonam in patients with cSSTI regardless of age and presence of comorbidities.

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Source: Wilcox M., Yan J. L., Gonzalez P. D. Impact of underlying comorbidities on outcomes of patients treated with ceftaroline fosamil for complicated skin and soft tissue infections: pooled results from three phase III randomized clinical trials. Infect Dis Ther 2022 Feb; 11 (1): 217–230, doi: 10.1007/s40121-021-00557-w.