Question

• Are older children with sickle cell anemia as vulnerable as younger children for the development of pneumococcal bacteremia in the absence of penicillin prophylaxis and can penicillin prophylaxis be discontinued for these patients?

Clinical Bottom Lines

1. After 5 years of age, children with sickle cell anemia who have not had prior pneumococcal infection or surgical splenectomy and are receiving comprehensive care have a low risk of developing pneumococcal bacteremia or meningitis regardless of the use of prophylactic penicillin.

Summary of Key Evidence

1. Eligible subjects included children with hemoglobin SS or hemoglobin S b°-thalassemia¹
2. All patients received prophylactic penicillin for at least 2 years before their 5th birthday
3. All patients received 23-valent pneumococcal vaccine between 2-3 years of age and at the time of study entry
4. Patients received either PCN VK (250 mg BID) or identical placebo tablet. 200 patient were in each study arm
5. Follow up averaged 3 years per child
6. Assumptions: (based on PROPS I data)
• 12% receiving placebo would have pneumococcal bacteremia or meningitis
• PCN prophylaxis would reduce incidence by 67%
• 4% of PCN group would have an infection
7. Results:
8. 1% in PCN group developed infection vs. 2% in placebo
9. None of the children died of infectious causes
10. Non-study antibiotic usage (for otitis, etc.) was equivalent
11. Those children who developed infection had very small increases in IgG titers to pneumococcus

Additional Comments

• The above data would suggest that PCN prophylaxis could be stopped at 5 years of age in children without a history of pneumococcal infection or surgical splenectomy.  However, it is difficult to determine whether the lack of difference in the two study groups was due to natural resistance to pneumococcal infection after this age or due to efficacy of the pneumococcal vaccine. The assumptions of disease prevalence was based on the PROPS I data which may not apply in this population since all had received pneumococcal vaccination prior to study entry.
• Potential justification for cessation of PCN prophylaxis after 5 years of age include patient convenience, drug costs (though low for PCN VK), and the possibility of emergence of more PCN-resistant pneumococcal strains.
• If prophylactic antibiotic use were discontinued, it is imperative that these children receive continuing comprehensive care and are routinely screened for bacteremia with all febrile illnesses.

Citation

1. Faletta JM, et al. Discontinuing penicillin prophylaxis in children with sickle cell anemia, J. Pediatrics 127: 685-690, 1995.

CAT Author: Dennis W. Kim, MD

CAT Appraisers: John G. Frohna, MD

Date appraised: November 18, 1999