Sickle cell disease: penicillin prophylaxis reduced severe streptococcus pneumoniae infection in young children.

Clinical bottom line (level 1b)

  1. Children under three years old with sickle cell anaemia who were given penicillin V, were less likely to get a severe streptococcus pneumoniae infection than those given vitamin C alone (NNT = 9 at 15 months) .
  2. There was no clear difference in other infections or deaths from pneumococcal septicaemia between the two groups.
Gaston et al: New England Journal of Medicine 1986; 314 (25): 1593-1599
Expires February 2003

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: twelve centres, USA

215 patients (aged range 3 to 36 months; mean 18, 50% male) sickle cell anaemia- SS haemoglobin pattern on electrophoresis and varying amounts of foetal haemoglobin

Excluded if
  • >3 years old
  • on long-term antibiotics/transfusion therapy
  • known penicillin allergy
  • signs or symptoms of infection


    • Control Group: (n = 105, 105 analysed): 50 mg vitamin C twice daily, crushed with food
    Experimental Group: (n = , analysed): 125 mg tablet penicillin V twice daily, crushed with food

    100% followed for 15 months

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    severe streptococcus pneumoniae infection 15 months 13
    (12.4%)    		 2
    (1.82%)    		 85.0%
    (36.0% to 97.0%)    		 10.6%
    (3.79% to 17.3%)    		 9
    (6 to 26)
    other infection (H. influenzae, E. coli) 15 months 4
    (3.81%)    		 2
    (1.82%)    		 52.0%
    (-155% to 91.0%)    		 1.99%
    (-2.44% to 6.42%)    		 50
    (NNT = 16 to infinity;
    NNH = 41 to infinity)
    deaths from pneumococcal septicaemia 15 months 4
    (3.81%)    		 1
    (0.91%)    		 76.0%
    (-110% to 97.0%)    		 2.90%
    (-1.17% to 6.97%)    		 34
    (NNT = 14 to infinity;
    NNH = 86 to infinity)

  • No allergic reactions were noted.

    • Comments

    1. Should these result apply now we have good pneumococcal vaccines?
    2. Compliance was assessed by pill counts at three monthly visits.
    3. The trial was terminated eight months early due to the number of episodes of pneumococcal septicaemia.
    4. Many professional bodies have emphasized the need for antibiotic prophylaxis and pneumococcal vaccine in children with sickle cell anaemia until the age of 5 years.

    Citation

    1. Gaston MH, Verter JI, Wood SG, et al: Prophylaxis with oral penicillin in children with sickle cell anemia: a randomised trial. New England Journal of Medicine 1986; 314 (25): 1593-1599
    Contributor: Chris Ball and Clare Wotton, February 2000
    Reviewer: Mona Nabulsi

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