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

Abstract

Introduction In three phase III randomized controlled trials, ceftaroline fosamil was shown to be non-inferior to vancomycin plus aztreonam for the treatment of complicated skin and soft tissue infections (cSSTIs). This exploratory analysis evaluated the impact of underlying comorbidities on clinical outcomes in patients with cSSTI pooled from these three studies. Methods CANVAS 1 and 2 and COVERS evaluated ceftaroline fosamil (600 mg every 12 h [q12h]; 600 mg every 8 h [q8h; COVERS]) versus vancomycin plus aztreonam (1 g q12h each [CANVAS 1 and 2]; vancomycin 15 mg/kg q12h and aztreonam 1 g q8h [COVERS]) in hospitalized adults with cSSTI. The primary efficacy variable in each trial was clinical response at the test-of-cure (TOC) visit. Subgroup analyses were performed on the pooled clinically evaluable (CE) population, exploring the impact of age and various baseline comorbidities. Results Overall, 1808 patients were included in the CE population (1005 ceftaroline fosamil; 803 vancomycin plus aztreonam). Clinical cure rates at TOC were 89.7% (ceftaroline fosamil) and 90.8% (vancomycin plus aztreonam) (difference [95% confidence interval] − 1.13 [− 3.87, 1.67]). Clinical response rates were similar between treatment groups, regardless of age (≤ 65 years or > 65 years), and in subgroups of patients with and without diabetes mellitus, peripheral vascular disease, cancer/malignancy, renal impairment, and obesity; within these subgroups, efficacy and safety results were generally consistent with those of the overall cSSTI population. Conclusions This analysis provides supportive evidence of the efficacy of ceftaroline fosamil in patients with cSSTI and underlying comorbidities. Trial Registration CANVAS 1, NCT00424190 and CANVAS 2, NCT00423657 (both trials first posted on ClinicalTrials.gov 18/01/2007); COVERS, NCT01499277 (first posted on ClinicalTrials.gov 26/12/2011). Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00557-w.

Clinical evidence supporting ceftaroline fosamil and ceftobiprole for complicated skin and soft tissue infections

“…The overall cure rate for the CE population with cancer/malignancy was 89.7% and 91.1%, respectively; for the CE population with moderate renal impairment 84.8% and 78.4%, respectively; and for the CE population with obesity 89.2% and 88.5% respectively. Microbiological eradication of MRSA was found at the TOC visit in 94.4% and 80.0%, respectively of the elderly CE population; in 82.4% and 68.8%, respectively of the diabetic CE population; and in 82.4% and 68.8%, respectively of the CE population with peripheral vascular disease [23].…”

“…In the attempt to better decipher the efficacy of ceftaroline among the more severe patients, separate subgroup analysis of all three phase III trials have been published for patients with bacteremia [22] and comorbidities [23]. In total, 46 patients allocated to ceftaroline and 39 patients allocated to comparator treatment had secondary bacteremia; their clinical cure rate was 80.4% and 84.6%, respectively.…”

Comprehensive guidance for antibiotic dosing in obese adults: 2022 update

“…Adequacy of ceftaroline 600 mg every 12 h was further corroborated by clinical success in 281/315 (89.2%) obese patients (BMI ≥30 kg/m 2 ) treated with ceftaroline for diabetic foot infections and complicated SSTI from retrospective registry data and subset analysis of phase III clinical trials. 53 More data are needed regarding use of more intensive dosing regimens, for example, 600 mg every 8 h, used by some for deep-seated, serious MRSA infections.…”

Skin and soft tissue diseases and their treatment in society

“…These organisms are all susceptible to penicillin or ampicillin, which should be administered in high doses. [20] Etiology Acute interstitial myositis caused by anaerobic streptococcal myonecrosis resembles subacute clostridial gas gangrene in terms of clinical presentation. Three to four days after an accident, edoema and a large amount of seropurulent exudate are the first symptoms to appear.…”