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.
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.
Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, Ohio, USA. Filet@summahealth.org
Thomas M
TM
File
Donald E
DE
Low
Paul B
PB
Eckburg
George H
GH
Talbot
H David
HD
Friedland
Jon
J
Lee
Lily
L
Llorens
Ian
I
Critchley
Dirk
D
Thye
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000009:adverse effects*; D002511:Cephalosporins / Q000008:administration & dosage* / Q000009:adverse effects*; D017714:Community-Acquired Infections / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D016896:Treatment Outcome; D000097583:Ceftaroline
D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D002511:Cephalosporins; D000097583:Ceftaroline