FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia.
ABSTRACT 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 (http://clinicaltrials.gov/ct2/show/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.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram-negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community-acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted.12/2013; 2(2):95-110. DOI:10.1007/s40121-013-0010-x
[Show abstract] [Hide abstract]
ABSTRACT: Gram-positive bacteria to include methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), and enterococci, to include vancomycin-resistant enterococci (VRE), display a remarkable array of resistance and virulence factors, which have contributed to their prominent role in infections of the critically ill. Over the last three decades infections with these pathogens has increased as has their overall resistance to available antimicrobial agents. This has led to the development of a number of new antibiotics for the treatment of Gram-positive bacteria. At present, it is important that clinicians recognize the changing resistance patterns and epidemiology of Gram-positive bacteria as these factors may impact patient outcomes. The increasing range of these pathogens, such as the emergence of community-associated MRSA clones, emphasizes that all specialties of physicians treating infections should have a good understanding of the infections caused by Gram-positive bacteria in their area of practice. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has traditionally been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for alternative agents demonstrating efficacy in this role. Similarly, the expansion of VRE as a pathogen in the ICU setting has required the development of agents targeting this important pathogen.BMC Infectious Diseases 01/2014; 14(1):92. DOI:10.1186/1471-2334-14-92 · 2.56 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Ceftaroline fosamil (ceftaroline hereafter) is the latest addition to the armamentarium for the treatment of patients with community-acquired pneumonia (CAP). It is currently approved by the Food and Drug Administration (FDA) for community-acquired bacterial pneumonia (CABP), which is a recent FDA indication that centers on individuals with documented bacterial pneumonias that arise in the community setting. The purpose of this review is to summarize and discuss the major findings from the Phase III CAP clinical trials as well as the clinical experience with ceftaroline among patients with CAP in the “Ceftaroline Assessment Program and Teflaro® Utilization Registry” (CAPTURE). In its two Phase III CAP trials, ceftaroline was compared to ceftriaxone among adults with radiographically confirmed CAP requiring hospitalization who were classified as Pneumonia Outcomes Research Team (PORT) risk class III or IV. Among patients with CAP, clinical success at test of cure was 84.3% vs 77.7% (difference 6.6%, 95% confidence interval [CI]: 1.6–11.8%) in those treated with ceftaroline and ceftriaxone, respectively, across the two Phase III clinical trials. Among patients with a culture-confirmed CABP, day 4 response rates were numerically higher, albeit non-significant, among patients that received ceftaroline vs. ceftriaxone (69.5% for ceftaroline vs. 59.4% for ceftriaxone, difference 10.1%, 95% CI, −0.6% to 20.6%). The efficacy of ceftaroline is supported by real-world observational data from CAPTURE for patients with both CAP and CABP. In addition, the CAPTURE program afforded an opportunity to assess the outcomes of patients who were excluded or limited in the original Phase III trials in a non-comparative fashion. These underrepresented patient populations with CAP included: patients that received prior antibiotics, patients in the ICU, patients with severe renal dysfunction, and those with methicillin-resistant Staphylococcus aureus (MRSA) isolated from respiratory or blood culture. As CAPTURE is a retrospective, non-comparator convenience sample registry, all the findings need to be interpreted with caution. Electronic supplementary material The online version of this article (doi:10.1007/s40121-014-0036-8) contains supplementary material, which is available to authorized users.09/2014; 3(2). DOI:10.1007/s40121-014-0036-8