Meningococcemia as a model for testing the hypothesis of antisepsis therapies

Objective: To critically review the advantages and disadvantages of pediatr ic meningococcemia as a model for testing antisepsis therapies. Data Sources: Research and review articles on the pathogenesis and treatmen t of human meningococcemia, as well as editorial commentaries discussing th e failure of clinical trials for adult sepsis or Systemic Inflammatory Resp onse Syndrome. Data from these sources are presented in the context of the author's experience as principal investigator in a large, randomized trial on children with invasive meningococcal disease. Study Selection and Data Extraction: Studies were selected to include aspec ts of epidemiology, pathophysiology, outcome prediction, and therapeutic tr ials. Data Synthesis: Compared with an adult sepsis population, meningococcemia i s a single disease, diagnosed clinically with high reliability. Patients ar e previously healthy, without underlying medical or surgical conditions. In contrast to sepsis trials, nearly all patients with meningococcal disease receive effective antibiotics. Finally, meningococcemia most closely resemb les animal models of endotoxin infusion, in which most antisepsis therapies have been highly effective. However, the meningococcal model carries major disadvantages, among them th at meningococcemia is rare and rapidly progressive and patients are widely dispersed geographically. In addition, a wide range of experimental therapi es is routinely provided in an attempt to preserve life or limbs. Conclusions: Meningococcemia is an ideal model of a rapidly progressive bac terial infection associated with marked endotoxemia. Problems with the mode l can be overcome by extensive pretrial logistic planning, as well as close coordination and cooperation with national regulatory agencies.