Penicillin doses may need to be increased as youngsters are getting heavier, The Daily Telegraph has reported. The newspaper said that dosing guidelines for penicillin and related antibiotics have not changed for almost 50 years, and are mostly based on children's ages rather than their weight.
This story is based on a review that examined how recommended doses of penicillin drugs have changed over the last 60 years. The review said that adult guidelines have been revised several times but that children’s penicillin guidelines have not been updated since the late 1950s. This means that doses are too low for today’s children. Currently, the British National Formulary for Children recommends different doses of penicillins depending on the individual drug and the condition being treated. For example, sometimes a dose recommendation is given by weight (such as amoxicillin for the treatment of ear infection), but in other cases the dose may be decided using age ranges (such as amoxicillin for the treatment of urinary tract infection). Prescription guidelines may also vary slightly from the dosing information provided by the manufacturer.
The review’s authors call for an evidence-based re-evaluation of the guidelines, to ensure that the most effective doses are given. The current review suggests that dosing guidelines provide ineffective levels of the medication, which could have consequences for both effective treatment and antibiotic resistance. Any review of clinical guidelines will need to consider both the most appropriate doses for children and instructions that prescribers can follow easily.
Where did the story come from?
The study was carried out by researchers from the University of London, King’s College London, the University of Athens, the University of Hong Kong and Boots the Chemist.
The study was published in the peer-reviewed British Medical Journal.
The media covered this study appropriately, with the BBC providing commentary on both the pros and cons of any change in dosing guidelines. However, while many newspapers concentrated on the childhood obesity angle, the review focussed on the lack of evidence for the initial guidelines and the lack of periodic review of these dosing guidelines. The review mentioned changes in children’s weight over the years (due to both obesity and changes in growth patterns), and that these should be accounted for when reviewing the guidelines in future.
What kind of research was this?
This narrative review looked at the dosing guidelines for children’s penicillin over the past 60 years. Penicillins are a large group of antibiotics that all work in a similar way and are used in the treatment of a wide range of infections. In addition to the two drugs named penicillin (penicillins G and V), the group includes many widely used related drugs, including amoxicillin and flucloxacillin.
Narrative reviews such as this can serve as springboards for important policy discussions, but on their own do not provide sufficient evidence for making policy changes.
Antibiotics are widely prescribed, for both children and adults, but setting the right dose is important. Under-dosing may not kill enough of the bacteria causing an infection, leading to the need for retreatment, the development of antibiotic resistance and an increase in the risk of severe complications. Giving a larger dose than necessary carries a risk of toxicity. With penicillins, such risks include, in rare cases, salt and water imbalance in the body or brain inflammation. Therefore, it is important that the proper dose is taken.
What did the research involve?
The researchers conducted a historical review of the scientific literature and UK pharmaceutical guidelines. They reviewed the evidence base for initial dosing guidelines drawn up in the 1950s, and examined how these guidelines have changed over the years. Next, using the dosing guidelines and recent demographic data, the researchers calculated the amount of penicillin today’s children receive, and compared these figures to the recommended doses.
What were the basic results?
The authors found that initial penicillin dosing guidelines were based on the child’s weight, but that these quickly gave way to dosing based on age. In 1963, the British Medical Journal published a general recommendation that age bands be used to determine antibiotic dose, regardless of the type of drug or the disease being treated. These recommendations have not changed since they were first published nearly 50 years ago.
British National Formulary (BNF) dosing guidelines for children’s penicillin V (phenoxymethylpenicillin), published in the early 1960s, have not changed either. The BNF lists the following age-based doses, which are usually prescribed four times a day:
- a maximum adult dose of 1,000mg
- 500mg for 12 to 18 years old
- 250mg for 6 to 12 years old
- 125mg for 1 to 5 years olds
- 62.5mg for under 1 year old
These guidelines are based on the following weight assumptions:
- 30kg for 10-year-olds
- 18kg for 5-year-olds
- 13kg for 2-year-olds
- 10kg for those under 1 year old
Recent UK survey data suggest that the average 5-year-old weighs 21kg, not the 18kg assumed in 1963, while the average 10-year-old weighs 37kg rather than the 30kg estimated at the time. The authors calculate that in practice, a 10-year-old who weighs 40kg receives 18mg of penicillin for each kg of weight a day, instead of the recommended 40-90mg/kg/day.
How did the researchers interpret the results?
The authors said that they “were surprised at the lack of recent evidence to support the BNF’s current dosing recommendations for such commonly used drugs as oral penicillins”. They said that under-dosing can lead to the need for retreatment, increase the risk of severe complications and encourage antibiotic resistance.
This was a narrative review of an important area of medicine: the appropriate prescription of antibiotics for children. The authors’ call for an evidence-based update of prescribing guidelines appears to be well founded, particularly as dosing guidelines for adult penicillin and related antibiotics have been updated several times over the last 50 years. During this time, adult doses have increased substantially. The authors say it is time for the same type of review to be applied to children’s dosage guidelines, and this would be likely to support increasing the doses given to children.
While this narrative review has highlighted the evidence behind the current guidelines for prescribing penicillins to children, and suggested ways these can be updated and improved, it is not intended to set new guidelines on dosage. Updating and standardising the clinical guidelines or prescribing formularies on child penicillins is likely to need to look at a wider range of evidence, and include considerations of the over-prescribing of antibiotics as well as antibiotic resistance.
Antibiotic resistance is of increasing concern all over the world, and arises in part due to inappropriate use of the drugs, as well as doses that are too low. Using penicillin in situations where it will be ineffective at knocking out target bacteria will provide them with an opportunity to adapt to the drug. This can lead to strains of bacteria evolving that do not respond to standard antibiotics.
Currently, the British National Formulary for Children recommends different doses of penicillins depending on the individual drug and the condition being treated. For example, for some conditions it gives a dose recommendation by weight, such as 40mg/kg of amoxicillin for an ear infection. However, for others it is by age group. For example, doses of amoxicillin for a urinary tract infection are given by the age categories 1-12 months, 1-5 years and 5-18 years. The manufacturer’s dosing information accompanying branded preparations may also be slightly different. The dosing regimen for penicillin V from the 1960s was based on the idea that a big child is half an adult, a small child is half a big child, and an infant is half a small child. Such recommendations would be unlikely to pass the evidence-based scrutiny of the current appraisal process for new drugs, but have become accepted and unquestioned since they were inherited from a time when the approval process was less robust.
The review points out that a similar policy discussion recently occurred regarding the use of children’s anti-retroviral (anti-HIV) medication. This discussion resulted in the overhaul of prescribing guidelines for these drugs, and the standardisation of practice across Europe. The authors suggest that a similar discussion is now needed for children’s penicillins, and that updated and standardised guidelines will ensure that the most effective dose is provided, reducing the need for repeat treatment and lowering the risk of antibiotic resistance.