“Hurts less, lasts longer” experiences of young people receiving high-dose subcutaneous infusions of benzathine penicillin G to prevent rheumatic heart disease
Authors: Cooper Julie , Enkel Stephanie L , Moodley Dhevindri , Dobinson Hazel , Andersen Erik , Kado Joseph H , Barr Renae K , Salman Sam , Baker Michael G , Carapetis Jonathan R , Manning Laurens , Anderson Anneka , Bennett Julie 
Published: September 2023

Background

Four-weekly intramuscular (IM) benzathine penicillin G (BPG) injections to prevent acute rheumatic fever (ARF) progression have remained unchanged since 1955. A Phase-I trial in healthy volunteers demonstrated the safety and tolerability of high-doseSubCutaneous Infusions of BPG (SCIP) which resulted in a much longer effective penicillin exposure, and fewer injections. Here we describe the experiences of young people living with ARF participating in a Phase-II SCIP trial.

Methodology

Participants (n=20) attended a clinic in Wellington, New Zealand (NZ). After a physical examination, participants received 2% lignocaine followed by 13.8mL (6 vials) to 20.7mL (9 vials) of BPG (Bicillin-LA®; determined by weight), into the abdominal subcutaneous tissue. Semi-structured interviews and observations were taken during and after the infusion, as well as on days 28 and 70. All interviews were recorded, transcribed verbatim, and thematically analysed.

Principal Findings

Low levels of pain were reported on needle insertion, during and following the infusion. Some participants experienced discomfort and bruising on days one and two post dose; however, the pain was reported to be less severe than their usual IM BPG. Participants were ‘relieved’ to only need injections quarterly and the overwhelming majority preferred to continue with SCIP.

Conclusions

Participants preferred SCIP over their usual regimen, reporting less pain and a preference for the longer time gap between treatments. Recommending SCIP as standard of care for most patients needing long-term ARF/RHD prophylaxis has the potential to transform secondary prophylaxis of ARF/RHD in NZ and globally.

Synopsis

Acute rheumatic fever (ARF) is a preventable inflammatory disease that occurs as a delayed sequelae to group A streptococcus (GAS) infection. ARF and its complication rheumatic heart disease (RHD) have significant negative effects on health, often resulting in chronic illness and premature death. For 70 years, the only proven way to prevent ARF progression has been benzathine penicillin G (BPG), given as a monthly intramuscular (IM) injection for a minimum of 10 years. The effectiveness of this approach is limited by pain and the frequency of injection which leads to suboptimal adherence. There is an urgent need to improve penicillin formulations for all children living with ARF and RHD. Here we describe the experiences of 20 young people living with ARF participating in a Phase-II trial delivering high-doseSubCutaneous Infusions ofPenicillin (SCIP) in order to provide longer effective penicillin exposure, and therefore fewer injections. Participants in the trial overwhelmingly preferred high-dose SCIP over their usual monthly IM penicillin regimen, reporting less pain and a preference for the longer time gap (28 versus 70 days) between treatments. Reducing injection frequency from 13 to four-or-five per year, may improve adherence and reduce disease progression. Offering widespread SCIP to ARF/RHD patients to evaluate long-term adherence, preferences and disease progression has the potential to transform secondary prophylaxis of ARF/RHD both in New Zealand and globally.