title: A pharmacokinetic/pharmacodynamic analysis of ceftaroline prophylaxis in patients with external ventricular drains.
abstract: BACKGROUND
  Ceftaroline is a broad-spectrum cephalosporin antibiotic with activity against drug-resistant bacteria, including strains of methicillin-resistant Staphylococcus aureus (MRSA), and may be useful to prevent and treat ventriculostomy-related infections (VRIs). The purpose of this study was to analyze the pharmacokinetics and pharmacodynamics of prophylactic ceftaroline in neurosurgical patients with an external ventricular drain (EVD).
  
  
  METHODS
  Adult patients in the neurosurgical intensive care unit with an EVD were given prolonged prophylaxis with ceftaroline. Serum and cerebral spinal fluid (CSF) were obtained simultaneously at 2, 6, and 12 h after initiation of the fourth dose of ceftaroline and concentrations were measured by a liquid chromatography tandem mass spectrometry assay. Time-kill curves against isolates of coagulase-negative S. aureus, methicillin-sensitive S. aureus, MRSA, and Streptococcus pneumoniae were determined in serum and CSF at each collection time point.
  
  
  RESULTS
  A total of five patients with a mean age of 63 y and mean weight of 83 kg were enrolled. The mean CSF:serum penetration ratios of ceftaroline were 0.005 (0.5%), 0.021 (2.1%), and 0.043 (4.3%) at 2, 6, and 12 h, respectively. The mean ceftaroline exposure ratio area under the curve (AUC)csf/AUCserum) was 0.011 (1.1%). Bactericidal activity at each collection time point was observed against each strain of staphylococci from serum samples and a penicillin-sensitive strain of S. pneumoniae from CSF samples.
  
  
  CONCLUSIONS
  This investigation suggests that ceftaroline could have clinical utility for the prevention of VRIs in patients with EVDs.
authors.affiliation: 1 Department of Medicine, Michigan State University , East Lansing, Michigan.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Stein
authors.forename: Fadi
authors.initials: F
authors.lastname: Yasin
authors.forename: Curtis
authors.initials: C
authors.lastname: Smith
authors.forename: Amy
authors.initials: A
authors.lastname: Scharmen
authors.forename: Daniel
authors.initials: D
authors.lastname: Havlichek
authors.forename: Charles
authors.initials: C
authors.lastname: Bill
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis / Q000706:statistics & numerical data*; D002511:Cephalosporins / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004322:Drainage / Q000009:adverse effects / Q000295:instrumentation*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D013210:Staphylococcus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097583:Ceftaroline