Less penicillin needed to treat Strep A infection than we thought

It turns out the concentration of penicillin required to fend off Strep A infection is less than half the amount used in treatment protocols delivered to patients for the past 75 years, according to a novel human challenge study.

The Controlled Human Infection for Penicillin Against Streptococcus (CHIPS) Trial — led by researchers at the Wesfarmers Centre of Vaccines and Infectious Diseases, based at The Kids Research Institute Australia — saw participants purposely infected with Streptococcus pyogenes (Strep A). Responsible for painful sore throats, acute rheumatic fever (ARF) and rheumatic heart disease (RHD), Strep A can also lead to life-threatening kidney disease, sepsis and heart failure.

Patients diagnosed with RHD are required to endure painful intramuscular benzathine penicillin G injections once a month over a 10-year period to avoid further infections. Lead researcher Laurens Manning, Head of Strep A & ARF Therapeutics research at the Wesfarmers Centre, explained that researchers decided back in the 1950s that 20 nanograms of penicillin per millilitre should be the target concentration in the bloodstream for long-acting penicillin — but this assumption was never actually tested.

“It’s never been known exactly how much penicillin prevents sore throats — the most common symptom of a Strep A infection,” said Manning, who is also an associate professor at The University of Western Australia’s Medical School.

“The ‘20’ figure became the golden number to adhere to … but injections delivered into the muscle at that concentration are extremely painful, which makes sticking to the monthly schedule very challenging, and many patients do not receive all their required treatments.”

The new study saw 60 participants infected with a well-studied, safe strain of Strep A, with Manning explaining that the researchers “were able to use cutting-edge science to evaluate patient responses to various levels of penicillin, at super fine margins, to determine the minimum effective penicillin exposure”. Their results, published in the journal The Lancet Microbe, showed that just 8.1 nanograms of penicillin per millilitre were required to prevent infection.

“Now that we have a clear target, we can accelerate development of new, long-acting injections, ideally into the skin rather than the muscle, that are considerably less painful and can be given at three-month intervals instead of monthly,” Manning said.

“This outcome is very exciting as it underpins everything we have been working on in this space — with these advances in delivery methods and efficiency, we hope to see longer-acting injections embedded in Australia’s national guidelines within the next few years and, in turn, see a dramatic rise in patients receiving the critical treatment they need to prevent potentially deadly rheumatic fever recurrence.”

Image credit: The Kids Research Institute Australia.