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).
From the *Cerexa, Inc, Oakland, CA; and †Forest Research Institute, Inc, Jersey City, NJ.
Correspondence to: Paul B. Eckburg, MD, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Dr, Grant S-101D, Stanford, CA 94305. E-mail: email@example.com.
Cerexa, Inc, is a wholly owned subsidiary of Forest Laboratories, Inc, New York, NY.
This work was supported by Cerexa, Inc. Funding for editorial assistance was provided by Forest Laboratories, Inc. Cerexa, Inc, and Forest Laboratories, Inc, were involved in the design of the study; collection, analysis, and interpretation of data; and decision to present these results. Cerexa, Inc, conducted the study, prepared the statistical analysis plan (SAP), and performed the analyses. The authors retained full control of the article content and its conclusions.
Author contributions: Dr Eckburg was the medical monitor and was involved with study design and data interpretation and serves as the guarantor of the entire manuscript. Drs Friedland and Eckburg contributed to the SAP; analysis of study data; and writing, editing, and approval of internal study reports. Drs Witherell and Laudano outlined the content of the manuscript and wrote the first draft. Dr Llorens and Mr Smith were involved with the design of the SAP, interpretation of the study data, and verification of study information. Dr Thye played a primary role in study design; design of the SAP; supervision of study conduct; training and oversight of clinical operations staff; analysis of data; and writing, editing, and approval of internal study reports. All listed individuals contributed to the preparation and approval of this article.
Sandra L. Ruhl, RN (Cerexa, Inc), and John A. Romankiewicz, PharmD (Scientific Therapeutics Information, Inc, Springfield, NJ), provided medical writing and editorial assistance on this article.
Drs Friedland and Llorens, and Mr Smith are employees of Cerexa, Inc; Drs Eckburg, Witherell, and Thye were employees of Cerexa, Inc, and Dr Laudano was an employee of Forest Research Institute, Inc, at the time the work and analyses were performed. Drs Eckburg, Friedland, Llorens, Witherell, and Thye, and Mr Smith, hold stock/stock options in Forest Laboratories, Inc.
Trial registration: ClinicalTrials.gov identifiers: NCT00621504 for FOCUS 1 and NCT00509106 for FOCUS 2.