No Demonstrable Benefit of Penicillin in a Vaccinated Population of Children with Sickle Cell Disorder

UK and many National guidelines advise on the use of prophylactic antibiotics, immunisation and patient education to minimise the risk of severe infections by encapsulated organisms in patients with Sickle Cell Disorder. The UK vaccination schedule for sickle cell anaemia patients includes Pneumococcal, Meningococcal and Haemophilus influenzae type B (Hib) immunisation. Prophylactic Penicillin V is recommended as additional protection against Streptococcus pneumoniae (S.pneumoniae).

In light of the findings in the papers by Oligbu et al, 2017, and Martin et al 2018, we aimed to retrospectively compare compliance with prophylactic Penicillin V against infection rates by S.pneumoniae,Neisseria meningitidis (N.meningitidis) and Hib . We hypothesised that the incidence of infections with IPD and other encapsulated organisms would be greater in patients who were not adherent with Penicillin V. Patients were considered compliant with prophylactic Penicillin V if 75% or more of their urine samples gave positive results.

The study population consisted of 52 Sickle Cell patients, ranging from age 3 to 20years.

Three patients were excluded as no urine samples had been collected from them in the 5 year period. Of the remaining 49 patients only 9 patients (18%) were had good adherence with Penicillin V over a 5 year period.

100% of patients received prevenar vaccination (PCV-7 or PCV 13).

73% received additional pneumovax.

We retrospectively reviewed microbiology culture reports over a five year period. All microbiology reports were reviewed from the period, with the virulent encapsulated organisms of S.pneumoniae,N.meningitidis and Hib recorded, alongside any other bacterial infections.

No patients had microbiological evidence of infection by virulent encapsulated bacteria. Six patients had cultures positive for other organisms: two Staphylococcus aureus positive sputum cultures, one Salmonella positive stool culture, two urine cultures positive for Escherichia coli, and one skin wound swab positive for Streptococcus pyogenes.

Of the 6 organisms identified, 3 occurred in patients compliant with Penicillin V, and 3 occurred in patients who were non-compliant. Patients compliant with Penicillin V formed a small cohort (n=9), resulting in an apparently high incidence of infection (33%). In the non-compliant cohort (n=40), 8% had shown infection. Analysis by Fisher's Exact Test confirmed no significant difference in the incidence of infection between the two groups (p= 0.06).

In a sickle cell disorder population where 82% of the patients were not 100% compliant with prophylactic Penicillin V, no significant encapsulated bacteria (S.pneumoniae,N.meningitidis or Hib) were cultured in a 5 year period in our cohort. Non-compliance with prophylactic Penicillin V was not associated with an increased incidence of infections by encapsulated organisms.

The UK study (Oligbu et al) on IPD was performed in the PCV13 era and states a 49x increased risk of developing IPD and a 5x increase in mortality in children with sickle cell compared to their peers. However, most IPD cases were due to non-vaccine serotypes. A similar study from the US (Martin et al) found deaths only in the PCV7 cohort, it does not state if the patients were vaccinated with pneumovax 23.

In conclusion 82% of children did not adhere to penicillin. We have not demonstrated any benefit in adhering to prophylactic penicillin. Adherence is poor and alternative approaches of standby antibiotics should be considered. We suggest focusing on vaccination as a preventative strategy is of more benefit. Martin OO, Moquist KL, Hennessy,JM, Nelson SC. Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era. Pediatr Blood Cancer. 2018;65:e26713. https://doi.org/10.1002/pbc.26713

Oligbu G, Collins S , Streetly A, Dick, M, Ladhany, S. Risk of invasive pneumococcal disease in children with sickle cell disease in England: National observational cohort study, 2010 - 2015. Arch Dis Child 2017;102(Suppl1):A4-A4