title: Ceftaroline fosamil versus ceftriaxone for the treatment of community-acquired pneumonia: individual patient data meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  We conducted a meta-analysis of clinical trials of adults hospitalized with pneumonia outcomes research team (PORT) risk class 3-4 community-acquired pneumonia (CAP) receiving ceftaroline fosamil versus ceftriaxone.
  
  
  METHODS
  Three Phase III trials (clinicaltrials.gov registration numbers NCT00621504, NCT00509106 and NCT01371838) including 1916 hospitalized patients with CAP randomized 1:1 to empirical ceftaroline fosamil (600 mg every 12 h) or ceftriaxone (1-2 g every 24 h) for 5-7 days were included in the meta-analysis. Primary outcome was clinical response at the test-of-cure visit (8-15 days after end of treatment) in the PORT risk class 3-4 modified ITT (MITT) and clinically evaluable (CE) populations. Data were tested for heterogeneity (χ(2) test) and, if not significant, results were pooled and OR and 95% CI constructed. A logistic regression analysis assessed factors impacting cure rate and treatment interactions.
  
  
  RESULTS
  Clinical cure rates in each trial consistently favoured ceftaroline fosamil versus ceftriaxone, with no evidence of heterogeneity. In the meta-analysis, ceftaroline fosamil was superior to ceftriaxone in the MITT (OR: 1.66; 95% CI 1.34, 2.06; P < 0.001) and CE (OR: 1.65; 95% CI 1.26, 2.16; P < 0.001) populations. Results were consistent across various patient- and disease-related factors including patients' age and PORT score. Prior antimicrobial use within 96 h of starting study treatment was associated with diminished differences in cure rates between treatments.
  
  
  CONCLUSIONS
  Ceftaroline fosamil was superior to ceftriaxone for empirical treatment of adults hospitalized with CAP. Receipt of prior antimicrobial therapy appeared to diminish the observed treatment effect.
authors.affiliation: AstraZeneca Research & Development, Biometrics & Information Sciences, Parklands, Alderley Park, Macclesfield, SK10 4TG, UK maria.taboada@astrazeneca.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Taboada
authors.affiliation: AstraZeneca, 1800 Concord Pike, Wilmington, DE 19803, USA.
authors.forename: David
authors.initials: D
authors.lastname: Melnick
authors.affiliation: AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Iaconis
authors.affiliation: AstraZeneca China, 1168 Nan Jing Xi Road, Shanghai, 200041, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Respiratory Diseases, 1st Affiliate Hospital of Respiratory Disease, Guangzhou Medical University, 151 Yan Jiang Road, Guangzhou, 501120, P.R. China.
authors.forename: Nan Shan
authors.initials: NS
authors.lastname: Zhong
authors.affiliation: Northeast Ohio Medical University, Rootstown, OH 44272, USA Summa Health System, Akron, OH 44304, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: File
authors.affiliation: Cerexa Inc., 2100 Franklin St, Oakland, CA 94612, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Llorens
authors.affiliation: Cerexa Inc., 2100 Franklin St, Oakland, CA 94612, USA.
authors.forename: H David
authors.initials: HD
authors.lastname: Friedland
authors.affiliation: AstraZeneca Research & Development, Biometrics & Information Sciences, Parklands, Alderley Park, Macclesfield, SK10 4TG, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wilson
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy*; D006801:Humans; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D002511:Cephalosporins; D000097583:Ceftaroline