Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease

Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors, contribute to persons with SCD being particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person-years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review which was first published in 2002, and previously updated, most recently in 2017.  OBJECTIVES: To compare the effects of antibiotic prophylaxis against pneumococcus in children with SCD receiving antibiotic prophylaxis compared to those without in relation to: 1. incidence of Streptococcus pneumoniae infection; 2. mortality (as reported in the included studies); 3. drug-related adverse events (as reported in the included studies) to the individual and the community; 4. the impact of discontinuing at various ages on incidence of infection and mortality.

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 also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform (not in 2020 given access issues relating to Covid-19 pandemic). Additionally, we carried out hand searching of relevant journals and abstract books of conference proceedings. Date of the most recent search: 25 January 2021.

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

The standard methodological procedures expected by Cochrane were used. Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the certainty of the evidence.

Six trials were identified by the searches, of which three trials were eligible for inclusion. A total of 880 children, who were between three months to five years of age at randomization were included. The included studies were conducted in centres in the USA and in Kingston, Jamaica. In trials that investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-certainty evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-certainty evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five years. Overall, the certainty of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias).

The evidence examined was determined to be of low certainty and suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.