Literature DB >> 21067350

Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia.

Thomas M File1, Donald E Low, Paul B Eckburg, George H Talbot, H David Friedland, Jon Lee, Lily Llorens, Ian Critchley, Dirk Thye.   

Abstract

BACKGROUND: Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin with bactericidal activity against pathogens causing community-acquired pneumonia (CAP), including Streptococcus pneumoniae. Ceftaroline was evaluated for the treatment of CAP in 2 randomized, double-blind, multicenter trials: Ceftaroline Community Acquired Pneumonia Trial versus Ceftriaxone in Hospitalized Patients (FOCUS) 1 and FOCUS 2.
METHODS: Patients hospitalized (but not admitted to an intensive care unit) with Pneumonia Outcomes Research Team risk class III or IV CAP requiring intravenous therapy were randomized to ceftaroline 600 mg every 12 h or ceftriaxone 1 g every 24 h for 5-7 days. Patients in FOCUS 1 received 2 doses of oral clarithromycin 500 mg every 12 h on day 1.
RESULTS: In the individual trials, clinical cure rates in the clinically evaluable (CE) population for ceftaroline versus ceftriaxone were as follows: FOCUS 1, 86.6% vs 78.2% (difference, 8.4%; 95% confidence interval [CI], 1.4%-15.4%); FOCUS 2, 82.1% vs 77.2% (difference, 4.9%; 95% CI, -2.5% to 12.5%). In the integrated analysis, 614 patients received ceftaroline and 614 received ceftriaxone. Of the CE patients treated with ceftaroline, 84.3% achieved clinical cure, compared with 77.7% of ceftriaxone-treated patients (difference, 6.7%; 95% CI, 1.6%-11.8%). Clinical cure rates in the modified intent-to-treat efficacy population were 82.6% versus 76.6% for ceftaroline and ceftriaxone (difference, 6.0%; 95% CI, 1.4%-10.7%). Ceftaroline and ceftriaxone were well tolerated; rates of adverse events, serious adverse events, deaths, and premature discontinuations caused by an adverse event were similar in both treatment arms.
CONCLUSIONS: Ceftaroline was noninferior to ceftriaxone in the individual trials. In this integrated analysis, clinical cure rates for the ceftaroline group were numerically higher than those for the ceftriaxone group. Ceftaroline was well tolerated, with a safety profile similar to that of ceftriaxone.

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Year:  2010        PMID: 21067350     DOI: 10.1086/657313

Source DB:  PubMed          Journal:  Clin Infect Dis        ISSN: 1058-4838            Impact factor:   9.079


  57 in total

Review 1.  Colonization, pathogenicity, host susceptibility, and therapeutics for Staphylococcus aureus: what is the clinical relevance?

Authors:  Steven Y C Tong; Luke F Chen; Vance G Fowler
Journal:  Semin Immunopathol       Date:  2011-12-11       Impact factor: 9.623

Review 2.  Ceftaroline fosamil in the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.

Authors:  Thomas P Lodise; Donald E Low
Journal:  Drugs       Date:  2012-07-30       Impact factor: 9.546

3.  Penetration of Ceftaroline into the Epithelial Lining Fluid of Healthy Adult Subjects.

Authors:  Todd A Riccobene; Richard Pushkin; Alena Jandourek; William Knebel; Tatiana Khariton
Journal:  Antimicrob Agents Chemother       Date:  2016-09-23       Impact factor: 5.191

Review 4.  Development of novel antibacterial drugs to combat multiple resistant organisms.

Authors:  Matteo Bassetti; Elda Righi
Journal:  Langenbecks Arch Surg       Date:  2015-02-11       Impact factor: 3.445

5.  Ceftaroline activity against bacterial pathogens frequently isolated in U.S. medical centers: results from five years of the AWARE surveillance program.

Authors:  Helio S Sader; Robert K Flamm; Jennifer M Streit; David J Farrell; Ronald N Jones
Journal:  Antimicrob Agents Chemother       Date:  2015-02-02       Impact factor: 5.191

Review 6.  Update in pulmonary infections 2010.

Authors:  Richard G Wunderink; Grant W Waterer
Journal:  Am J Respir Crit Care Med       Date:  2011-07-15       Impact factor: 21.405

7.  Assessment of time to clinical response, a proxy for discharge readiness, among hospitalized patients with community-acquired pneumonia who received either ceftaroline fosamil or ceftriaxone in two phase III FOCUS trials.

Authors:  Thomas P Lodise; Antonio R Anzueto; David J Weber; Andrew F Shorr; Min Yang; Alexander Smith; Qi Zhao; Xingyue Huang; Thomas M File
Journal:  Antimicrob Agents Chemother       Date:  2014-12-08       Impact factor: 5.191

8.  The biomarkers consortium.

Authors:  David Wholley
Journal:  Nat Rev Drug Discov       Date:  2014-11       Impact factor: 84.694

Review 9.  South African guideline for the management of community-acquired pneumonia in adults.

Authors:  Tom H Boyles; Adrian Brink; Greg L Calligaro; Cheryl Cohen; Keertan Dheda; Gary Maartens; Guy A Richards; Richard van Zyl Smit; Clifford Smith; Sean Wasserman; Andrew C Whitelaw; Charles Feldman
Journal:  J Thorac Dis       Date:  2017-06       Impact factor: 2.895

Review 10.  Antimicrobial Therapy in Community-Acquired Pneumonia in Children.

Authors:  Samriti Gupta; Rakesh Lodha; S K Kabra
Journal:  Curr Infect Dis Rep       Date:  2018-09-20       Impact factor: 3.725

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