Sickle cell disease: penicillin prophylaxis in children older than five was not clearly necessary.

Clinical bottom line (level 1b-)

  1. Children aged at least five years old with sickle cell disease who were given continuing penicillin prophylaxis, had no clear difference in infection than those whose penicillin was stopped, but there was a trend towards more infection without penicillin.
  2. There was no clear difference in adverse effects between penicillin and placebo.
Falletta et al: Journal of Pediatrics 1995; 127 (5): 685-690
Expires February 2003

The study

Double-blinded ?concealed randomised trial without intention-to-treat
Setting: 18 centres, USA

400 patients (aged mean 5 years, 53% male) children with sickle cell disease aged more than 5, and had been on penicillin prophylaxis for at least 2 years before their fifth birthday. They also had to have received 23-valent pneumococcal vaccination aged 2 to 3 and a repeat one since.

Excluded if
  • history of documented bacteraemia or meningitis by streptococcus pneumoniae or haemophilus influenzae b
  • penicillin allergy
  • splenectomy
  • on long-term transfusion programme


    • Control Group: (n = 103, 103 analysed): placebo
    Experimental Group: (n = 115, 115 analysed): penicillin 125 mg po twice daily
    If a child had febrile illness (temperature >38 ° C) then blood cultures were taken. If the child had been started on antibiotics, the study drug was discontinued until the course was finished.
    100% followed for 3 years
    Outcome notes:
    • adverse effects : nausea, vomiting or both

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    streptococcus pneumoniae systemic infection 3 years 4
    (3.88%)    		 2
    (1.74%)    		 55.0%
    (-139% to 92.0%)    		 2.14%
    (-2.29% to 6.57%)    		 47
    (NNT = 15 to infinity;
    NNH = 44 to infinity)
    systemic infection from other organism 3 years 3
    (2.91%)    		 2
    (1.74%)    		 40.0%
    (-250% to 90.0%)    		 1.17%
    (-2.86% to 5.21%)    		 85
    (NNT = 19 to infinity;
    NNH = 35 to infinity)
    adverse effects 3 years 1
    (0.97%)    		 2
    (1.74%)    		 -79.0%
    (-1850% to 84.0%)    		 -0.77%
    (-3.82% to 2.28%)    		 -130
    (NNT = 44 to infinity;
    NNH = 26 to infinity)

  • Four children died (two in each group), but none of these were due to infection.

    • Comments

    1. Note the exclusion of children with previous illness or splenectomy.
    2. Better pneumococcal vaccines may make penicillin prophylaxis unnecessary.
    3. Also note concerns re: the worldwide increase in the prevalence of penicillin - resistant pneumococci.

    Citation

    1. Falletta JM, Woods GM, Verter JI, et al: Discontinuing penicillin prophylaxis in children with sickle cell anemia. Journal of Pediatrics 1995; 127 (5): 685-690
    Search Terms: sickle in Cochrane
    Contributor: Chris Ball and Clare Wotton, February 2000
    Reviewer: Sudha Chaudhari

    Clinical Question.
    Patient sickle cell disease
    Intervention or Exposure penicillin
    Comparison placebo
    Outcome infection