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.
Author(s): File TM Jr, Low DE, Eckburg PB, Talbot GH, Friedland HD, Lee J, Llorens L,
Critchley I, Thye D.
Affiliation(s): Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown,
Ohio, USA. Filet@summahealth.org
Publication date & source: 2010, Clin Infect Dis. , 51(12):1395-405
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.
Erratum in
Clin Infect Dis. 2011 Apr 1;52(7):967.
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