Day 4 Clinical Response of Ceftaroline Fosamil Versus Ceftriaxone for Community-Acquired Bacterial Pneumonia

Abstract

In Brief Background Ceftaroline (active metabolite of ceftaroline fosamil) was efficacious in 2 phase 3 community-acquired pneumonia (CAP) trials (FOCUS 1 and 2) using clinical cure rates at the test-of-cure visit. Recent US Food and Drug Administration guidelines for design of noninferiority CAP trials recommend evaluation of clinical response at 72 to 96 hours after initiating therapy (day 4) rather than traditional test of cure. The day 4 end point may be more clinically relevant with respect to hospital discharge and oral stepdown therapy. Methods A retrospective integrated analysis of the FOCUS trials was conducted in 309 adult patients with moderate to severe CAP and at least 1 proven typical bacterial pathogen at baseline. Patients received intravenous ceftaroline fosamil (600 mg) every 12 hours or ceftriaxone (1 g) every 24 hours for 5 to 7 days. Clinical response at day 4 included normalization of signs (fever, white blood cell count, blood pressure, respiratory rate) and improvement in respiratory symptoms (cough, dyspnea, sputum production, chest pain). Results Day 4 clinical response rates were 69.5% (107/154) for ceftaroline and 59.4% (92/155) for ceftriaxone (difference 10.1%; 95% confidence interval, −0.6% to 20.6%). In individual studies, absolute treatment differences of 14.1% (FOCUS 1) and 6.8% (FOCUS 2) favoring ceftaroline were observed. Clinical response rates at day 4 associated with the most common pathogens, Streptococcus pneumoniae (ceftaroline, 54/74 [73.0%]; ceftriaxone, 42/75 [56.0%]) and Staphylococcus aureus (ceftaroline, 14/24 [58.3%]; ceftriaxone, 17/31 [54.8%]), were numerically higher for ceftaroline. Conclusions Ceftaroline appears to provide clinical benefit over ceftriaxone at day 4 for treatment of community-acquired bacterial pneumonia. Ceftaroline was previously shown noninferior to ceftriaxone in clinical cure rate at the traditional test-of-cure visit in two pivotal Phase 3CABP trials (FOCUS 1 and FOCUS 2); however, clinical response at day 4 among subjects with a proven pathogen may be a more appropriate endpoint for such FDA registration trials. In this analysis from the FOCUS trials, ceftaroline had a nurmerically higher clinical response rate than ceftriaxone at day 4 (69.5% vs. 59.4%, respectively).