Session Speaker 21st Lancefield International Symposium for Streptococci and Streptococcal Diseases 2022

Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia (#79)

Joseph H Kado 1 2 , Sam Salman 1 2 3 , Robert Hand 1 4 , Margaret O'Brien 5 6 , Anna Ralph 6 7 , Asha Bowen 1 2 8 , Madhu Page-Sharp 9 , Kevin Batty 9 , Veronica Dolman 2 , Joshua Francis 6 7 , Jonathan Carapetis 1 2 8 , Laurens Manning 1 2 10
  1. Telethon Kids Institute, Nedlands, WA, Australia
  2. Medical School, University of Western Australia, Crawley, WA, Australia
  3. Clinical Pharmacology and Toxicology Unit, PathWest, Perth, WA, Australia
  4. Royal Perth Hospital, Perth, WA, Australia
  5. Danila Dilba Health Service, Darwin, NT, Australia
  6. Menzies School of Health Research , Charles Darwin University, Darwin, NT, Australia
  7. Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT, Australia
  8. Perth Children's Hospital, Nedlands, WA, Australia
  9. Curtin Medical School, Curtin University, Bentley, WA, Australia
  10. Fiona Stanley Hospital, Murdoch, WA, Australia

Background:   Benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections which precede acute rheumatic fever (ARF). The paucity of pharmacokinetic (PK) data from children and adolescents from populations at the highest risk of ARF and rheumatic heart disease poses a challenge for determining the optimal dosing and frequency of injections and undermines efforts to develop improved regimens. 

Methods:         We conducted a 6-month longitudinal PK study of young people receiving BPG for secondary prophylaxis. Throat and  skin swabs were collected for microbiological culture along with dried blood spot (DBS) samples for penicillin concentrations. DBS were assayed using LC-MS/MS. Penicillin concentration datasets were analysed using non-linear mixed-effects modelling and simulations performed using published BMI-for-age and weight-for-age data.

Results:            Nineteen participants provided 75 throat swabs, 3 skin swabs and 216 penicillin samples. Throat cultures grew Group C and G streptococcus (GCGS). Despite no participant maintaining penicillin concentration >20ng/mL between doses, there were no Streptococcus pyogenes throat infections and no ARF. The median (range) observed duration >20 ng/ml for the low- and high BMI groups were 14.5 (11.0-24.25) and 15.0 (7.5-18.25) days, respectively.

Conclusion:     Few patients at highest risk of ARF/RHD receiving BPG for secondary prophylaxis maintain penicillin concentrations above the target of 20ng/mL beyond 2 weeks during each monthly dosing interval. These PK data suggest that some high-risk individuals may get inadequate protection from 4-weekly dosing. Future research should explore this gap in knowledge and  PK differences between different populations to inform future dosing schedules.