Meningococcemia as a model for testing the hypothesis of antisepsis therapies.

Abstract

To critically review the advantages and disadvantages of pediatric meningococcemia as a model for testing antisepsis therapies. Research and review articles on the pathogenesis and treatment of human meningococcemia, as well as editorial commentaries discussing the failure of clinical trials for adult sepsis or Systemic Inflammatory Response 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. Studies were selected to include aspects of epidemiology, pathophysiology, outcome prediction, and therapeutic trials. Compared with an adult sepsis population, meningococcemia is a single disease, diagnosed clinically with high reliability. Patients are 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 resembles animal models of endotoxin infusion, in which most antisepsis therapies have been highly effective. However, the meningococcal model carries major disadvantages, among them that meningococcemia is rare and rapidly progressive and patients are widely dispersed geographically. In addition, a wide range of experimental therapies is routinely provided in an attempt to preserve life or limbs. Meningococcemia is an ideal model of a rapidly progressive bacterial infection associated with marked endotoxemia. Problems with the model can be overcome by extensive pretrial logistic planning, as well as close coordination and cooperation with national regulatory agencies.