title: Ceftaroline fosamil: a cephalosporin with activity against methicillin-resistant Staphylococcus aureus.
abstract: BACKGROUND
  Ceftaroline is a cephalosporin with expanded gram-positive activity recently approved for clinical uses by the US Food and Drug Administration.
  
  
  OBJECTIVE
  This article provides an overview of the in vitro and in vivo activities, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of ceftaroline.
  
  
  METHODS
  Relevant information was identified through a search of PubMed (1990-April 2011), EMBASE (1990-April 2011), International Pharmaceutical Abstracts (1970-April 2011), and Google Scholar using the key words ceftaroline, PPI-0903, PPI-0903M, T-91825, and TAK-599. A review of the reference lists of identified articles, a search of the US Food and Drug Administration Web site, and posters and abstracts from scientific meetings yielded additional publications.
  
  
  RESULTS
  In vitro, ceftaroline exhibits activity against most aerobic gram-positive isolates, common aerobic gram-negative respiratory pathogens, and some gram-positive anaerobes. The MIC range for most Staphylococcus aureus isolates, including vancomycin-resistant strains was between ≤0.008 and 4 μg/mL. In Phase III studies (CANVAS 1 and CANVAS 2), ceftaroline was found to be noninferior to vancomycin + aztreonam for the treatment of complicated skin and skin-structure infections, with a clinical cure rate of 91.6% among clinically evaluable patients (ceftaroline versus vancomycin + aztreonam: difference, -1.1; 95% CI, -4.2 to 2.0; P = NS). Ceftaroline's efficacy has also been assessed for the treatment of community-acquired pneumonia in 2 Phase III studies (FOCUS 1 and FOCUS 2) and was equivalent to ceftriaxone, with cure rates of 84.3% and 77.7%, respectively, among clinically evaluable patients in the combined analysis (ceftaroline versus ceftriaxone: difference, 6.7; 95% CI, 1.6 to 11.8). The recommended dosage for patients 18 years and older is 600 mg IV every 12 hours. Dosage adjustment is necessary in patients with renal impairment (creatinine clearance ≤50 mL/min). The pharmacokinetic properties of ceftaroline in patients with hepatic impairments are currently unavailable. Ceftaroline appeared to be well tolerated generally. The most frequently (>3%) reported adverse events were nausea, headaches, diarrhea, pruritus, rash, and insomnia; all were usually mild to moderate, self-limiting, and of little clinical significance.
  
  
  CONCLUSIONS
  Ceftaroline is a cephalosporin with broad gram-positive activity, including Methicillin-resistant S aureus and vancomycin-resistant S aureus. Its gram-negative activity includes common respiratory pathogens and members of the Enterobacteriaceae. Clinical trials have reported that ceftaroline was noninferior to ceftriaxone, and vancomycin + aztreonam for the treatment of community-acquired pneumonia and complicated skin and skin-structure infections, respectively.
authors.affiliation: Pharmacy Service, James J. Peters Veterans Affairs Medical Center, 130 West Kingsbridge Road (119), Bronx, NY 10468, USA. Henry.Poon@VA.gov
authors.forename: Henry
authors.initials: H
authors.lastname: Poon
authors.forename: Mei H
authors.initials: MH
authors.lastname: Chang
authors.forename: Horatio B
authors.initials: HB
authors.lastname: Fung
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097583:Ceftaroline