Open-Label Randomized Trial of Early Clinical Outcomes of Ceftaroline Fosamil Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections at Risk of Methicillin-Resistant Staphylococcus aureus

Abstract

Introduction Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection. Methods Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics. Results One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures ( n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%). Conclusion Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2–3 days, thus limiting our ability to critically assess clinical outcomes. Trial Registration ClinicalTrials.gov identifier, NCT02582203. Funding Allergan plc.

Baseline Characteristics and Outcomes Among Patients with Complicated Skin and Soft Tissue Infections Admitted to the Intensive Care Unit: Analysis of the Phase 3 COVERS Randomized Trial of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam

“…In line with the overall COVERS population [ 13 ] and the non-ICU subset, the most frequently isolated pathogens from patients in the ICU subset included S. aureus , streptococci, and Enterobacteriaceae. These findings are consistent with other prospective clinical studies in patients with cSSTI or ABSSSI [ 11 , 12 , 20 ] and retrospective epidemiological data [ 7 , 21 ]. Ceftaroline fosamil and vancomycin plus aztreonam were highly active in vitro against the most common pathogens isolated from patients in the ICU subset.…”

Ceftaroline Efficacy and Safety in Treatment of Complicated Skin and Soft Tissue Infection: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

“…Finally, five studies [15,16,17,18,19] meeting the inclusion criteria were included in this meta-analysis (Figure 1). All studies [15,16,17,18,19] were randomized, multicenter designed to compare the clinical efficacy and safety of ceftaroline with other comparators for adult patients with cSSSIs (Table 1). Overall, a total of 1326 and 1035 patients received ceftaroline and comparators, respectively.…”

“…Overall, a total of 1326 and 1035 patients received ceftaroline and comparators, respectively. All studies [16,17,18,19], except one [15], were multi-national. Four studies [16,17,18,19] compared monotherapy with ceftaroline and vancomycin-based combination therapy.…”

“…Four studies [16,17,18,19] compared monotherapy with ceftaroline and vancomycin-based combination therapy. One study [15] used ceftaroline with/without metronidazole in comparison with vancomycin/ceftriaxone/metronidazole combination therapy. Most of the domains in each study were classified as having a low risk of bias, except one study [15] with high risk of selection, performance, and detection bias (Figure 2).…”

“…According to the findings of these studies [8,9,10,11], ceftaroline can cover most common pathogens causing cSSSIs and can be an appropriate antibiotic for the treatment of cSSSIs. Recently, several randomized trials have assessed the clinical efficacy and safety of ceftaroline for treating cSSSIs and pneumonia in adult patients [12,13,14,15,16,17,18,19]. Regarding pneumonia, a recent meta-analysis showed that ceftaroline has a clinical efficacy rate of 81.2% and >70% success rate against pneumonia caused by S. pneumonia and S. aureus , respectively, including their multidrug-resistant pathogens [20].…”