Reducing the global burden of sepsis in infants and children: a clinical practice research agenda.

OBJECTIVE: Sepsis remains a predominant cause of mortality and morbidity in children in the developing and industrialized world. This review discusses a clinical practice research agenda to reduce this global burden.
DESIGN: Summary of the literature with analysis by experts.
RESULTS: Many interventions have been proven effective in decreasing sepsis. Heterologous immunization with attenuated Bacillus Camille Guerin vaccine reduces all-cause mortality, and specific immunizations further reduce morbidity and mortality from many specific microbes. Antepartum antibiotics reduce the prevalence of cerebral palsy and mortality in infants. Administration of antibiotics to neonates with signs of sepsis reduces all-cause mortality five-fold and can also reduce mortality in the big four killers of children: severe pneumonia, diarrhea, malaria, or measles. Immunonutrition with zinc and vitamin A can further reduce morbidity in diarrhea and pneumonia and reduce mortality in measles. First-hour rapid intravenous fluid resuscitation achieves 100% survival in dengue shock, and time-sensitive fluid resuscitation and inotropic support reduces mortality ten-fold in meningococcal septic shock. Multiple organ failure occurs when late or inadequate resuscitation results in systemic thrombosis or when infection is not eradicated because of immunosuppression or inadequate source control.
CONCLUSIONS: The global burden of sepsis can be reduced by 1) prevention with improved heterologous or specific vaccines and vitamin or mineral supplement programs; 2) early recognition and treatment with appropriate antibiotics, intravenous fluid resuscitation, and inotropic support in organized healthcare-delivery systems; and 3) development of new diagnostics and therapeutics that reduce systemic thrombosis, improve immune function, and kill resistant organisms.