Regular antibiotics for preventing pneumococcal infection in young children with sickle cell disease

People with sickle cell disease (SCD) are especially prone to respiratory infections and blood poisoning. These infections are often caused by pneumococcal bacteria. Infections occur partly due to the spleen not working correctly, but also because damaged tissue and bone resulting from SCD can harbour bacteria. The highest risk of infection occurs in children under three years old, but the usual pneumococcal vaccines are of limited use in these patients. Therefore regular antibiotics are needed to prevent infection. As risk of infection decreases with age, there might be a time when preventative antibiotic treatment can be halted. Three trials with over 800 children are included in the review. All three trials showed a reduced rate of infection in children with sickle cell disease receiving penicillin preventatively. Two trials looked at whether treatment was effective. The third trial followed on from one of the early trials and looked at when it was safe to stop treatment. Adverse drug effects were rare and minor. However, there were problems with children keeping to the treatment schedule and with the development of antibiotic resistance. We conclude that penicillin given preventatively reduces the rate of pneumococcal infections in children with sickle cell disease under five years old. The risk of infection in older children is lower, and the follow-on trial did not show a significant increase in risk when regular penicillin was halted at five years old. Further research should look at how common and how clinically important resistant bacteria are.

Authors' conclusions: 

Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

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Background: 

This is an update of a Cochrane Review first published in 2002, and previously updated in 2012. People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population.

Objectives: 

To assess the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease.

Search strategy: 

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Date of the most recent search: 26 June 2014.

Selection criteria: 

All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug.

Data collection and analysis: 

Both authors independently extracted data and assessed trial quality.

Main results: 

Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with sickle cell disease (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five.

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