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28 March 2022

There are many challenges associated with antibiotic resistance; understanding the optimal use of antibiotics for children is one of the most poignant. The overuse and misuse of antibiotics is steadily contributing to antimicrobial resistance which in turn is making these drugs increasingly ineffective.

Various types of oral penicillin contribute to 5 out of the 8 million prescriptions for oral antibiotics given to children in England every year. The most common reasons for prescriptions among children are an ear infection or symptoms including sore throat and cough.

This current research, led by Professor Paul Long, which took place between 2011-2020, has shown that age-band dosing guidelines have not been changed since 1963. Additionally, there was a huge variation in prescribing practices, with many children not receiving the optimal doses.

When aiming to eliminate bacteria that is causing an infection, the antibiotic concentration where the infection is happening in a patient, e.g., the inner ear, needs to be maintained above the minimum inhibitory concentration (MIC) for the bacteria causing the infection. Penicillins work in a time-dependent mechanism to kill bacteria: the longer the time that the antibiotic concentration in the infected tissue is above the MIC, the greater the killing effect of the antibiotic. In the event of antibiotic underdosing, the antibiotic concentration does not surpass the MIC or only attains the MIC for a short period of time. Therefore, the antibiotic activity is reduced. This leaves the bacteria exposed to non-lethal antibiotic doses, fuelling antibiotic resistance by allowing bacteria to mutate and evolve rather than being killed.

The team of researchers in this study undertook an extensive search of the literature and relevant historical formularies dating back to the first world war. They uncovered evidence of the age band regime and revealed that the current UK dosing schedule was based on a principle of halving adult oral penicillin doses for older children and simply halving for younger children and infants. This entire principle is arbitrary and has remained unchallenged since its introduction in 1963. Essentially, a 10-year-old child who weighs 30kg would, with this reasoning, receive 25mg per day which is a very low dose.

To investigate this further, the team reviewed data collected by GP practises from 2011-12, finding that there was a wide variation in the dosing of penicillin for children but also, that 55% of children were being underdosed. The situation was even worse in higher age bands, and it became clear that fluctuations in the weight of young people as well as a general increase in obesity need to be considered when setting these dosage limits.

This situation could be down to learned behaviour of GPs – prescribing a certain dose and seeing the children get better.

Professor Paul Long

The data used in this study formed part of a review of UK paediatric antibiotic dosing guidelines, led by a consortium for improving children’s antibiotic prescribing (from King’s, UCL and Imperial) which was then used as evidence by the Joint Formulary Committee to support changes to the UK prescribing guidelines in 2014. As a result of the recommendations from this committee, the UK’s prescribing guidelines were updated later that year and rolled out across the NHS. Today the guidelines have been adopted by approximately 40 countries worldwide.

Raising awareness is one thing – but changing behaviour and practice, as Professor Long’s research has done, paves the way for better patient outcomes across the world.

Professor Dame Sally Davies, ex-Chief Medical Officer
HealthTechnology & Science

In this story

Paul Long

Professor in Pharmacognosy