FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia.

Mount Sinai Hospital/University Health Network, Toronto, Ontario, Canada.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.31). 04/2011; 66 Suppl 3:iii33-44.
Source: PubMed


Ceftaroline (active form of the prodrug ceftaroline fosamil) is a novel cephalosporin with activity against pathogens commonly associated with community-acquired pneumonia (CAP), including Streptococcus pneumoniae and Gram-negative pathogens. This randomized, double-blind, Phase III study evaluated the efficacy and safety of ceftaroline fosamil in treating patients with CAP. The primary objective was to determine non-inferiority [lower limit of 95% confidence interval (CI) ≥ -10%] of clinical cure rates achieved with ceftaroline fosamil compared with those achieved with ceftriaxone in the clinically evaluable (CE) and modified intent-to-treat efficacy (MITTE) populations.
Patients hospitalized in a non-intensive care unit setting with CAP of Pneumonia Outcomes Research Team (PORT) risk class III or IV requiring intravenous (iv) therapy were randomized (1:1) to receive 600 mg of ceftaroline fosamil iv every 12 h or 1 g of ceftriaxone iv every 24 h. Clinical cure, microbiological response, adverse events (AEs) and laboratory tests were assessed. FOCUS 2 registration number NCT00509106 (
The study enrolled 627 patients, 315 of whom received ceftaroline fosamil and 307 of whom received ceftriaxone. Patients in both treatment groups had comparable baseline characteristics. Clinical cure rates were as follows: CE population, 82.1% (193/235) for ceftaroline fosamil and 77.2% (166/215) for ceftriaxone [difference (95% CI), 4.9% (-2.5, 12.5)]; and MITTE population, 81.3% (235/289) for ceftaroline fosamil and 75.5% (206/273) for ceftriaxone [difference (95% CI), 5.9% (-1.0, 12.7)]. Clinical cure rates for CAP caused by S. pneumoniae in the microbiological MITTE (mMITTE) population were 83.3% (35/42) and 70.0% (28/40) for ceftaroline fosamil and ceftriaxone, respectively. Ceftaroline fosamil and ceftriaxone were well tolerated, with similar rates of AEs, serious AEs, deaths and discontinuations due to an AE. The most common AEs for ceftaroline fosamil-treated patients were diarrhoea, headache, hypokalaemia, insomnia and phlebitis, and the most common AEs for ceftriaxone-treated patients were diarrhoea, insomnia, phlebitis and hypertension.
Ceftaroline fosamil achieved high clinical cure and microbiological response rates in patients hospitalized with CAP of PORT risk class III or IV. Ceftaroline fosamil was well tolerated, with a safety profile that is similar to that of ceftriaxone and other cephalosporins. Ceftaroline fosamil is a promising agent for the treatment of CAP.

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    • "Cerexa (a wholly owned subsidiary of Forest Laboratories) was involved in the design, collection, analysis, interpretation of data, and decision to present these results. The FOCUS trials (NCT00621504 and NCT00509106) were global, double-blind, randomized, multicenter , multinational, noninferiority, phase III studies in patients hospitalized for moderate to severe CABP (Patient Outcomes Research Team [PORT] risk class III or IV) requiring intravenous (IV) antimicrobial therapy (File et al., 2010, 2011; Low et al., 2011). Prior to study initiation, all sites received approval from their institutional review board or independent ethics committee, and all patients provided written informed consent. "
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    ABSTRACT: Ceftaroline fosamil resulted in higher cure rates than ceftriaxone in patients with community-acquired bacterial pneumonia in 2 randomized trials (FOCUS 1 and FOCUS 2). The present analysis examines the subgroup of patients with Streptococcus pneumoniae infection to determine whether the apparent difference in cure rates persists after adjusting for potential covariates. We retrospectively pooled subjects with S. pneumoniae isolated at baseline in the original studies and employed logistic regression to evaluate the independent relationship between clinical cure and treatment with ceftaroline. Covariates evaluated included demographics, severity of illness, bacteremia, and pathogen characteristics. The final cohort included 139 subjects (69 ceftaroline, 70 ceftriaxone). Unadjusted cure rates were 85.5% and 68.6% (P = 0.009) in the ceftaroline and ceftriaxone groups, respectively. After logistic regression, ceftaroline remained associated with higher cure rates. Our findings indicate that ceftaroline may result in improved outcomes of S. pneumoniae pneumonia. Formal clinical trials are warranted to confirm this hypothesis.
    Full-text · Article · Jan 2013 · Diagnostic microbiology and infectious disease
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    ABSTRACT: Community-acquired pneumonia (CAP) is a serious condition associated with significant morbidity and potential long-term mortality. Although the majority of patients with CAP are treated as outpatients, the greatest proportion of pneumonia-related mortality and healthcare expenditure occurs among the patients who are hospitalized. There has been considerable interest in determining risk factors and severity criteria assessments to assist with site-of-care decisions. For both inpatients and outpatients, the most common pathogens associated with CAP include Streptococcus pneumoniae, Haemophilus influenzae, group A streptococci and Moraxella catarrhalis. Atypical pathogens, Gram-negative bacilli, methicillin-resistant Staphylococcus aureus (MRSA) and viruses are also recognized aetiological agents of CAP. Despite the availability of antimicrobial therapies, the recent emergence of drug-resistant pneumococcal and staphylococcal isolates has limited the effectiveness of currently available agents. Because early and rapid initiation of empirical antimicrobial treatment is critical for achieving a favourable outcome in CAP, newer agents with activity against drug-resistant strains of S. pneumoniae and MRSA are needed for the management of patients with CAP.
    Preview · Article · Apr 2011 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Ceftaroline fosamil, the prodrug of the active metabolite, ceftaroline, is a new, broad-spectrum cephalosporin recently approved in the USA for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP). Ceftaroline has potent in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae, as well as common Gram-negative organisms. The high affinity of ceftaroline for penicillin-binding proteins is responsible for the potent activity observed against clinically relevant pathogens. With respect to the treatment of CABP, the activity of ceftaroline against pathogens such as S. pneumoniae, S. aureus, Haemophilus influenzae and Moraxella catarrhalis demonstrates coverage across a broad range of pathogens typically encountered in clinical practice. Ceftaroline is also very active against common pathogens seen in ABSSSIs such as S. aureus (methicillin-susceptible S. aureus and methicillin-resistant S. aureus) and Streptococcus pyogenes. Ceftaroline exhibits a dose-proportional pharmacokinetic profile, similar to other renally excreted cephalosporins, and has a well-tolerated safety profile consistent with the cephalosporin class. Ceftaroline fosamil is compatible via Y-site administration with many other commonly administered parenteral drugs.
    Full-text · Article · Apr 2011 · Journal of Antimicrobial Chemotherapy
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