title: Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies.
abstract: BACKGROUND
  We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF/MEN/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials provides an opportunity for improving the characterization of outcomes.
  
  
  METHODS
  A retrospective analysis of placebo-controlled, open-label, and compassionate-use trials was conducted. Adult patients received infusions of either DrotAA or placebo. All pediatric patients (<18 years old) received DrotAA. 189 adult and 121 pediatric patients presented with PF/MEN/MD.
  
  
  RESULTS
  Fewer adult patients with PF/MEN/MD met cardiovascular (68.3% versus 78.8%) or respiratory (57.8% versus 80.5%) organ dysfunction entry criteria than those without. DrotAA-treated adult patients with PF/MEN/MD (n = 163) had an observed 28-day mortality rate of 19.0%, a 28-day serious bleeding event (SBE) rate of 6.1%, and an intracranial hemorrhage (ICH) rate of 4.3%. Six of the seven ICHs occurred in patients with MEN (three of whom were more than 65 years old with a history of hypertension). DrotAA-treated adult patients without PF/MEN/MD (n = 3,088) had an observed 28-day mortality rate of 25.5%, a 28-day SBE rate of 5.8%, and an ICH rate of 1.0%. In contrast, a greater number of pediatric patients with PF/MEN/MD met the cardiovascular organ dysfunction entry criterion (93.5% versus 82.5%) than those without. DrotAA-treated PF/MEN/MD pediatric patients (n = 119) had a 14-day mortality rate of 10.1%, an SBE rate of 5.9%, and an ICH rate of 2.5%. DrotAA-treated pediatric patients without PF/MEN/MD (n = 142) had a 14-day mortality rate of 14.1%, an SBE rate of 9.2%, and an ICH rate of 3.5%.
  
  
  CONCLUSIONS
  DrotAA-treated adult patients with severe sepsis presenting with PF/MEN/MD had a similar SBE rate, a lower observed 28-day mortality rate, and a higher observed rate of ICH than DrotAA-treated patients without PF/MEN/MD. DrotAA-treated pediatric patients with severe sepsis with PF/MEN/MD may differ from adults, because all three outcome rates (SBE, mortality, and ICH) were lower in pediatric patients with PF/MEN/MD.
authors.affiliation: Department of Intensive Care, University of Brussels, Erasme Hospital, Brussels, Belgium. jlvincen@ulb.ac.be
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Simon
authors.initials: S
authors.lastname: Nadel
authors.forename: Demetrios J
authors.initials: DJ
authors.lastname: Kutsogiannis
authors.forename: R T Noel
authors.initials: RT
authors.lastname: Gibney
authors.forename: S Betty
authors.initials: SB
authors.lastname: Yan
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Wyss
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey
authors.forename: Carol L
authors.initials: CL
authors.lastname: Mitchell
authors.forename: Samiha
authors.initials: S
authors.lastname: Sarwat
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Shinall
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Janes
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D006801:Humans; D011695:IgA Vasculitis / Q000453:epidemiology*; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D008297:Male; D016920:Meningitis, Bacterial / Q000453:epidemiology*; D008589:Meningococcal Infections / Q000453:epidemiology*; D008875:Middle Aged; D016017:Odds Ratio; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000453:epidemiology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated