Benzathine penicillin G (BPG), delivered as an intramuscular (IM) injection every 3-4 weeks has been the cornerstone of secondary prophylaxis to prevent recurrent streptococcal infections and subsequent rheumatic fever for more than 70 years. Successful delivery of BPG is hampered by the pain and inconvenience of regular IM injections. In parallel, there have been limited efforts to improve the formulation of BPG and ensure sustainable access to high quality preparations for those who need it most.
Based on population pharmacokinetic (PK) studies conducted in diverse populations, most people receiving IM BPG do not sustain concentrations above the historically accepted target between injections. Inadvertent subcutaneous injections have favourable PK profiles and high-dose subcutaneous infusions of BPG (SCIP), which can be delivered every 10 weeks are feasible, cost effective and preferred among Maori and Pasifika young people in Phase-II trials of SCIP. When compared with IM delivery, SCIP provides better penicillin exposure at all plausible protective target concentrations, lower than the historically accepted target which has been informed by a recent human challenge trial.
To accompany recent developments with SCIP, the pipeline for a new formulation of BPG is promising with a number of novel preparations in pre-clinical animal studies. An improved formulation should be manufactured in a pre-filled syringe, be injectable through a 25G needle and be the smallest possible volume to minimise injection pain. Licensure will include subcutaneous delivery on the product insert. To ensure equitable global access, it should be stable at tropical temperatures and priced ethically.