Penicillin Prophylaxis in Sickle Cell Disease (PROPS)

BACKGROUND:

For over 20 years children with sickle cell anemia have been known to have an increased susceptibility to severe bacterial infection, particularly due to Streptococcus pneumoniae. Meningitis, pneumonia and septicemia due to this organism have been recognized as the major causes of death for these children, with children under three years of age being at highest risk. The annual incidence of pneumococcal septicemia among young children with sickle cell anemia appears to have remained remarkably constant over the last two decades at approximately 10 percent. This illness can often be fulminant, progressing from the onset of fever to death in less than 12 hours, with a case fatality rate ranging as high as 35 percent.

Penicillin prophylaxis has been advocated as a preventive measure against severe pneumococcal infections in children with sickle cell anemia. One study had shown that the risk of pneumococcal infection in these children could be reduced by the use of parenteral penicillin.

DESIGN NARRATIVE:

Phase I was a multi-center, randomized, double-blind, placebo-controlled trial. One hundred and five patients were assigned to the penicillin group and 110 to placebo. The primary endpoint was a documented severe infection due to S. pneumoniae. The secondary endpoint was a severe infection due to an organism other than S. pneumoniae.