Paediatric penicillins - getting the dose right

Welcome to the Australian Prescriber Podcast. Australian Prescriber, independent, peer-reviewed and free.

I'm Dhineli Perera, your host for this episode. It's a pleasure to be speaking to Dr Brendan McMullan.

Brendan is a paediatric infectious diseases specialist and microbiologist working at Sydney Children's Hospital. Brendan and Mona write about the best prescribing practices for penicillins in children. Brendan, welcome to the program.

Thanks very much Dhineli.

Okay, so Brendan, let's start with the critical take-home message from your article, which is where should health professionals look for up-to-date dosing advice for penicillins in children?

Thanks Dhineli. There are several good sources for up-to-date advice. So as we mentioned in the article, Therapeutic Guidelines has up-to-date and evidence-based advice, and there are other sources such as the Australian Medicines Handbook for children. Many children's hospitals also have advice on their websites with antibiotic recommendations for a whole range of conditions.

Okay, great. So they would be your go-to references. I guess, what is the issue with using product information? So that's information from the manufacturers. Why are these sources of information not your go-to?

Yeah. Good question. So product information is obviously important, but recommendations in the product information may only include indications and doses that were approved by the Therapeutic Goods Administration at registration, and since most oral penicillin products in Australia have been used for more than 20 years now and a generally off patient, up-to-date dosing information may not be included in the product information, particularly for children.

Right. And why are these sources of info not updated?

So generally the update only occurs with new indications, and so there's very little appetite for updating this for commonly used well-established drugs like penicillins.

Right. Okay. So I think most listeners would be aware that common self-limiting infections and viral infections in children don't require antibiotics. However, your article mentions that bacterial infections requiring drainage or other physical treatment also fit into this group. Could you tell us more about this?

Yeah, that's right. So often skin abscesses and boils only require drainage and or local treatment to heal. Antibiotics are not needed for most cases. For some dental infections, for example, as well, the most important thing is timely dental treatment. So for these sorts of infections, the key is removing the physical source of the infection. So draining the puss or removing the infected tooth, and that's often enough to let the body's immune system do the rest of the job.

Right. So you don't need a course to mop up the bacteria that might be remaining?

Yeah, that's right. For most cases, that's the situation. For more detailed advice, doctors are able to make a decision as to whether antibiotics are also indicated and they can get further advice from Therapeutic Guidelines Antibiotic as well as speaking with a microbiologist or an infectious diseases physician, if needed.

And I think my understanding is that a lot of the time boils and things like that, the supply or the ability of the antibiotic to actually reach the side of infection is quite difficult, is that correct?

Yeah, that can definitely be a case with abscesses. So antibiotics in general only reliably reach places with a blood supply. So sometimes in the centre of a boil or an abscess, an antibiotic has limited ability to penetrate, whereas physically removing it by draining the boil can do the job. We do sometimes use antibiotics in conjunction with boils, for example, if there's associated cellulitis, we would sometimes use antibiotics as part of a decolonisation process. So there are instances where antibiotics are used, but in many cases, antibiotics are not required.

Right. Okay. Your article touches on the pharmacokinetics of children and how it differs to that of adults, especially in children less than two. Can you tell us a bit more about these differences?

Sure. So paediatricians like me and other child health providers really often say that children are not little adults. And we say that in this case, because when it comes to handling drugs, this is true for a number of reasons, so for example, infants in particular have a higher proportion of body water and that affects drug distribution. We also mentioned gastric acid in the article and how this changes during childhood, but liver and kidney function and metabolism also changes through infancy and childhood and this affects drug metabolism. So for this reason, we need to consider age when we're prescribing drugs for children.

Okay. As we enter winter, understanding the role of penicillins in community acquired pneumonia is important. Can you tell us when it is appropriate to prescribe amoxicillin alone versus amoxicillin clavulanic acid for this indication. I'm suspecting that it's a pretty commonly prescribed choice between both of them. So how do you prescribers decide?

Yeah. This question comes up quite a bit in my practice. So as we've mentioned, quite a lot of pneumonia and infections in children are due to viruses and supportive care rather than antibiotics is required. But in terms of bacterial pneumonia in children, the organism which causes a big majority of cases is Streptococcus pneumoniae, which is otherwise known as pneumococcus. Now amoxicillin with clavulanic acid offers no additional benefit over amoxicillin alone for treating infections due to this organism. In fact, amoxicillin with clavulanic acid may be less effective if, because of the way it's given, a lower dose of the amoxicillin component is actually prescribed.

So you could actually be doing harm by choosing amoxicillin clavulanic acid over amoxicillin alone?

Yeah. So theoretically, yes, if you were giving a lower amoxicillin dose, but an additional harm might be the fact that the clavulanic acid component does tend to cause additional gastrointestinal side effects in some children compared with amoxicillin alone.

And why is dosing based on age not always appropriate? I think you mentioned earlier that we have to consider age and not treat children as mini adults, but sometimes age isn't enough either.

Good question. So yes, absolutely. So age is important as we've discussed, but knowing their age on its own is not enough and this is especially when dosing, age-based dosing is based on broad age categories, for example, six to 12 years or 10 to 15 years. And the reason for that is principally there's a risk of under or overdosing. And this is especially at the extremes or the margins of those age bands. And we discussed this a bit in the article, but using the child's weight to help calculate the dose essentially enables us to avoid this error. So we always weigh children when they're admitted to hospital and that's one of the big reasons for this.

And in your article, Brendan, you run through a few examples of discrepancies between doses recommended in the product info versus Therapeutic Guidelines. Can you tell us about any that you see commonly cause an issue in practice?

Yeah, so the doses we give there are commonly under dosing, using the product information as opposed to up-to-date guidelines and I work mainly in hospitals, so this affects what I see rather than in the community, but across the board calculation errors are common in kids. So for this reason, it's good to have methods in place to double check doses, and so prescribers can do this and pharmacists are also great at this.

I do sometimes see children prescribed antibiotics in the community who need to come in to hospital who have been underdosed as we discussed in the article, or given doses, which aren't quite right, because someone's had to guess the weight and hasn't got it quite right, so for this reason, if you can, weighing children is a really important strategy to avoid this error.

Yeah. And I think the NPS actually had a great little video a few years ago about how to weigh children that may not be cooperative to stand on the scales and for the listeners out there that have that issue, it's just a matter of getting an adult to hold the child and then weighing the adult and the difference would be the weight of the child. And I think that's an issue that some parents often have that they don't really know, or they don't have a reliable way estimate at hand and when they're at home, they can do that nice and quickly and easily.

Absolutely. I've used that method in the past.

Yeah. Yeah, definitely. And finally, Brendan, with the issue of pack sizes and volumes, what do prescribers need to do to ensure adequate supply of the antibiotic is available to the patient?

Yeah. Good question. So for liquids, especially if you're prescribing a higher dose than is listed in the product information, if the product information's dosing is lower than what we'd recommend according to up-to-date guidelines, it's important that prescribers consider the product based on the volume that will be dispensed and select one that's suitable for the patient, so that also means you need to consider the duration. So how long is the child going to need to take this antibiotic?

It's not just taking a guess.

Yeah, exactly. You actually need to do the calculation. And there are ways to make that easier. Pharmacists will often get in contact with prescribers if there's something wrong with the dose or what's been prescribed can't be dispensed, but it's better to get it right at the beginning at the point of prescribing.

So some medicines given to children are tablets that can be crushed, but penicillins are often given as capsules. And so there are also a number of ways these can be opened for children and mixed with certain things so that they can take them easily depending on the situation. And there's lots of good online sources for information about that, you've mentioned NPS has great advice on a range of things, the SHPA, The Society of Hospital Pharmacists of Australia, has some really good advice on that, which is appropriate for children, but also for older people who can't swallow capsules, for example people who have feeding tubes and things like that.

Mm-hmm (affirmative).

So, there's a lot of really good information online. But if in doubt, I always suggest discussing with a pharmacist and for tricky issues regarding children, children's hospitals also have specialist pharmacists who can help point people in the right direction.

Mm-hmm (affirmative). Excellent. Okay. Well that's unfortunately all the time we've got for this episode, thanks so much for joining us today, Brendan.

Thanks very much for having me, Dhineli.

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The views of the hosts and guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Dhineli Perera and thanks for joining us on the Australian Prescriber Podcast.