S3 E1 Use of antibiotics in children

In this first episode of season 3, former RCPA President, Dr Lawrie Bott, and Paediatric Infectious Diseases Specialist and Microbiologist, Dr Brendan McMullan, discuss the use of antibiotics in children and what impact a recent global shortage of antibiotics has had in Australia. 

Transcript

00:00:00:22 - 00:00:16:18

Voiceover

Welcome to the Pathologists Cut podcast. This RCPA podcast explores the broad medical specialty of pathology and the critical role pathologists play in medicine and healthcare.

00:00:16:20 - 00:00:51:10

Dr Lawrie Bott

Hello and welcome to the RCPA’s Pathologists Cut podcast series. Today we will be talking to Dr Brendan McMullan about the use of antibiotics in children and what impacts recent global shortage of antibiotics has had in Australia. Dr McMullan is a paediatric infectious diseases specialist and microbiologist working at Sydney Children's Hospital, Randwick, and a senior research fellow in the Faculty of Medicine and Health in the discipline of paediatrics at University of New South Wales.

00:00:51:12 - 00:01:09:03

Dr Lawrie Bott

His research focuses on treatment of infections and improving antibiotic use in children. This includes research involving special groups such as immunocompromised children and newborns. Thank you for joining us today, Brendan.

00:01:09:05 - 00:01:11:14

Dr Brendan McMullan

Thanks very much, Lawrie, for having me.

00:01:11:16 - 00:01:32:05

Dr Lawrie Bott

Brendan, a report by the Australian Commission on Safety and Quality in Health Care found that the highest rate of antibiotic dispensing for people under the age of 65 was in children aged 2 to 4 years. That statistic might be surprising to some people. Can you explain this finding?

00:01:32:07 - 00:02:12:04

Dr Brendan McMullan

Yes. Thanks for asking, Lawrie. It’s a good point. And it may be surprising to people, given that children are a smaller proportion of the population, that we have so much antibiotic prescribing in that group. But to explain this further, children are a special group. They’re not just little adults and they are new to the world and encountering viruses and bacteria for the first time, which means that on average they get many more infections during the first few years of life than comparable groups of the population do until you get to older age groups.

00:02:12:06 - 00:02:55:21

Dr Brendan McMullan

So because children get infections more often, they are also prescribed medications to treat those infections more often. And principally, that includes antibiotics, especially for things like upper respiratory tract infections and otitis media. Some of these antibiotics are, in fact, unnecessary for what turn out to be viral infections. But some of these antibiotics are very important for bacterial infections, such as Group A streptococcus infections, Staphylococcus aureus infections and other infections that affect children.

00:02:55:23 - 00:03:00:05

Dr Lawrie Bott

Brendan, what are the main issues around the use of antibiotics in children?

00:03:00:07 - 00:03:31:24

Dr Brendan McMullan

Yes. Well, points to consider when prescribing antibiotics to children are that their body size is different from adults. And that means that the amount of antibiotics we give them is going to be proportionately reduced. We actually dose antibiotics for most children based on age or weight or sometimes age or weight bands. And so that’s complexity compared to prescribing for adult where often a single dose will be prescribed.

00:03:32:01 - 00:04:08:21

Dr Brendan McMullan

In addition, drug metabolism and toxicities do change during the lifespan, and that’s especially concentrated in that first few months of life, which affects the prescribing doses and the safety of medications in that age group. And, really importantly, swallowing and the formulation really do affect how well children are able to take antibiotics. So medicines often have to be prescribed in a liquid form or a form that can be made into something that a child can swallow rather than a tablet or a capsule.

00:04:08:23 - 00:04:35:01

Dr Brendan McMullan

And it has to be palatable. So if a medicine tastes awful, it’s going to be very hard to persuade that toddler to keep taking it even for a relatively short course of antibiotics. So those are just some of the considerations. Apart from that, as I mentioned, viral illnesses are common in this age group, and it can be hard sometimes to distinguish a viral from a bacterial illness, at least initially.

00:04:35:04 - 00:05:12:23

Dr Brendan McMullan

So general practitioners and paediatricians, however, are really good at working through that with the help of parents and carers. But it’s something that you need some experience and you learn with time. And the spectrum of organisms does also change a little bit across the age group, especially once again in those youngest months of life. So, the types of organisms causing infections in newborns like Group B streptococcus and sometimes severe E coli infections is not necessarily going to be very common once you get to a three-year-old or a 10-year-old.

00:05:13:00 - 00:05:25:14

Dr Lawrie Bott

So, Brendan, immunocompromised children are clearly such a challenge. That’s an area of your interest. Have you got any specific comments on that group of children?

00:05:25:16 - 00:05:58:12

Dr Brendan McMullan

Yeah, absolutely. So, children can be immunocompromised from different ways. So I really a key group within that population are children who are being treated for malignancy or cancer with chemotherapy. And those children are often looked after by specialised services who often work at tertiary children’s hospitals, although that may well be part of a shared care team with general practitioners or paediatricians from other hospitals and in primary care.

00:05:58:14 - 00:06:30:20

Dr Brendan McMullan

And these children may well be prescribed oral antibiotic therapy or antifungal therapy as prophylaxis. So, once again, we face the same issues with drug metabolism, toxicity, dosing based on age and weight, swallowing and formulation issues. But, also, this group of children may well need intravenous medicines. So not just their chemotherapy, but sometimes intravenous antibiotics or even antifungals when they have fever and neutropenia.

00:06:30:20 - 00:06:55:23

Dr Brendan McMullan

And, of course, the response to infection can be different and difficult to distinguish in a child compared to an adult. So, a two-year-old is not going to be able to localise and describe their symptoms in the same way that a 25-year-old or even a 12-year-old will be able to do. But, in addition to that, increasingly, as in adult medicine, we are seeing new groups of immunocompromised children.

00:06:55:23 - 00:07:28:22

Dr Brendan McMullan

So, children treated with immunosuppressive agents for autoimmune and rheumatological conditions is one group. Children with what are called inborn errors of immunity or primary immune deficiency is another group, and even we could consider the relative immunosuppression of the newborn infant who lacks that adaptive immunity, having never encountered these pathogens before. Apart from the offset that they get from placental transfer from their mother.

00:07:28:24 - 00:08:04:01

Dr Brendan McMullan

So, all of these things impact what we do with antibiotic therapy. And, I think once again, these are the kinds of things that influence the differences in prescribing amounts. So that 2 to 4 age group in the Australian Commission’s AURA [Antimicrobial Use and Resistance in Australia] 2021 report that has the highest group of PBS dispensed antibiotics in the community apart from the over 65 adults, That’s the group where children are often going to day care, interacting with other kids, getting viral infections and getting secondary bacterial infections.

00:08:04:03 - 00:08:31:11

Dr Brendan McMullan

They’ve no longer got the benefit of those placental antibodies and breastfeeding antibodies for the most part from their parents. They’re mixing with lots of other children. And it’s in that group that we see these frequent viral illnesses and sometimes antibiotic illnesses. And I think the big challenge is that that’s also a group that usually needs a liquid formulation or a crushed tablet formulation.

00:08:31:17 - 00:08:40:06

Dr Brendan McMullan

And we’ve seen shortages of those recently, partly contributed to by what’s been happening with Group A strep infections.

00:08:40:08 - 00:08:48:04

Dr Lawrie Bott

Is there any difference in the approach to the in-patient compared to the community infections?

00:08:48:06 - 00:09:19:21

Dr Brendan McMullan

Yeah, absolutely. So, for children who are unwell enough to receive in-patient care for a paediatric patient, we usually need to consider the child very explicitly in the context of their family and care community. So, it is usual for a caregiver, such as a parent, to stay with the child. The parent may be unwell themselves in some cases, but hopefully they’re well and able to deliver that additional care and support to the child.

00:09:19:23 - 00:09:42:14

Dr Brendan McMullan

So, we have to consider for children who need that in-patient care that the child is unable to sort of consent and understand things in the same way as an adult does. So, we have to involve the parent in that, and we have to have issues such as establishing intravenous access, sometimes for delivering antibiotics, fluids and other supportive things.

00:09:42:14 - 00:10:08:13

Dr Brendan McMullan

And that’s on average more difficult to obtain and maintain that intravenous access to the children compared to adults, which in some regards prompts us to really consider very early whether we can achieve a safe intravenous to oral antibiotics switch, for example, in children treated with infections. So that’s an area of research I’m very involved with, as are a number of my colleagues.

00:10:08:13 - 00:10:25:23

Dr Brendan McMullan

And I would say in paediatric medicine, in some ways we have set the benchmark for adult medicine in terms of opportunities for reviewing whether we can safely switch to oral antibiotics and then potentially transfer these children to complete their therapy at home.

00:10:26:00 - 00:10:39:18

Dr Lawrie Bott

Thanks, Brendan. Just going further into the community situation, is there a threshold in determining the need for antibiotics at all? Typically, it may be at the heart of it a viral infection.

00:10:39:20 - 00:11:16:18

Dr Brendan McMullan

Yeah. I think that’s a great question. So, yes, I think every opportunity where a child is seen by a healthcare provider with a suspected infection that is an opportunity to consider does this child have a viral or potentially a bacterial infection and do they need antibiotics now or in the future if they continue to deteriorate? So, there are a number of tools that can assist with those decision-making processes for GPs, primary care providers and others who see children.

00:11:16:20 - 00:11:57:01

Dr Brendan McMullan

So, for example, the Therapeutic Guidelines – Antibiotic [Therapeutic Guidelines – Antibiotic Prescribing in Primary Care], which are used as national guidelines in Australia and, potentially in some other places overseas, have a lot of good information to help GPs and other doctors who see children make a decision for children presenting with common conditions such as upper respiratory tract infections, fever and potential otitis media about whether or not that child needs an antibiotic now and what sort of antibiotic that should be, what the dose should be, etc. And part of that sometimes for these really common conditions involves a shared care process.

00:11:57:03 - 00:12:25:08

Dr Brendan McMullan

So that may be discussing what to expect with the parents and coming up with a plan for some children about not starting an antibiotic now, but giving a prescription with a plan to start that later if certain conditions are met, such as ongoing fever, deterioration, etc., with some with some safety messaging around that. But also considering that children who are at higher risk and need to start those antibiotics right now.

00:12:25:08 - 00:12:56:08

Dr Brendan McMullan

So, for example, certain of our First Nations children in communities that have higher rates of Group A streptococcal infection and rheumatic fever need to start those antibiotics directed against Group A strep if they’ve got a compatible illness straightaway and they need to be appropriately followed up for that. Certain children with features of severe disease or who are very young who present with otitis media are more likely to need to start antibiotics straightaway. 

00:12:56:08 - 00:13:21:16

Dr Brendan McMullan

And, for children with sore throats, there are some clinical criteria that can help GPs and other care providers stratify whether or not this particular sore throat is more likely to be viral or more likely to be bacterial. So, all of those things can help. But, I think, you know, the key thing is that this should be done in consultation with the parents and caregivers providing that extra education and support.

00:13:21:18 - 00:13:34:00

Dr Brendan McMullan

And, in terms of support to GPs and other care providers, look, there are always paediatricians and paediatric infection specialists who can provide additional advice as needed.

00:13:34:02 - 00:13:42:01

Dr Lawrie Bott

Brendan, there’s been a recent global shortage of antibiotics. What’s that meant for Australian children?

00:13:42:03 - 00:14:24:16

Dr Brendan McMullan

So, we have found a number of changes in the epidemiology of both viral and bacterial infections, especially in the period since the COVID pandemic. And, in particular, we’ve seen large increases in Group A strep infections in many parts of the world, including parts of Australia. So, that is certainly the case in New South Wales and Victoria – there’s been a large increase in Group A strep infections. Whereas in some parts of Australia, like the Northern Territory, they’ve sadly had very high rates of Group A strep infections, particularly in First Nations communities even preceding this.

00:14:24:18 - 00:14:52:00

Dr Brendan McMullan

But coinciding with this group of Group A strep infections and other infections, we’ve had a shortage of some of the most important oral antibiotics we use to treat these. So, antibiotics affected by the shortage include cephalexin, amoxicillin, phenoxymethylpenicillin (otherwise known as penicillin v), amoxicillin clavulanate (otherwise known as Augmentin) and trimethoprim sulfamethoxazole, something that is otherwise known as Bactrim or Septrin.

00:14:52:02 - 00:15:26:19

Dr Brendan McMullan

So those are really some of the most common antibiotics used to treat common infections in children. And when they've been all short to various degrees at the same time, it’s actually been quite a challenge to provide treatment for these children. And so the states, including, for example, New South Wales where I work, have used our Clinical Excellence Commission to kind of try and reach out to GPs and pharmacies and hospitals and share information and provide advice about how to manage those shortages.

00:15:26:24 - 00:16:02:15

Dr Brendan McMullan

And one of the things we can do, I think a bit more in Australia, is use information on tablets that can be safely crushed or capsules that can be opened and dispersed and mixed with something suitable for children. There’s a nice kind of information available in the Australian Medicines Handbook and available on various other venues with the ‘Don't Rush to Crush’ moniker, which gives people – prescribers – advice on which medicines can and can't be crushed or dispersed, made into a liquid or a more palatable formulation for children.

00:16:02:21 - 00:16:50:05

Dr Brendan McMullan

So we can certainly use that information to provide children with some of these antibiotics when the existing syrup formulations are out of stock. And pharmacists are a great source of knowledge about that. So GPs and other healthcare providers can talk with hospital pharmacists or potentially community pharmacists about available options there. It’s still not a perfect solution because one of the great things about syrup is it’s easy to provide an age-appropriate dose, whereas with tablets you may have a little bit of a calculation to do or possibly some wastage in terms of crushing the tablet, but at least we have some options there and sometimes we have to substitute one drug for another or obtain overseas stock.

00:16:50:05 - 00:16:59:19

Dr Brendan McMullan

And so that has been possible for a number of antibiotics using what’s called the SAS scheme.

00:16:59:21 - 00:17:05:16

Dr Lawrie Bott

What have the supply chain issues been in terms of a shortage, a global shortage?

00:17:05:18 - 00:17:42:02

Dr Brendan McMullan

So there have been supply chain issues. So, unfortunately, antibiotics are not made in a distributed fashion locally or internationally as much as we would like. And supply chain issues in one country can very much affect another country. The Therapeutic Goods Administration licenses particular types of these medicines. And so sometimes the same biologic product may not be a registered product in Australia if it’s produced by another country and made elsewhere.

00:17:42:02 - 00:18:10:06

Dr Brendan McMullan

So provision may have to be made for registering that product or bringing it in via an SAS scheme. But so, for example, in the UK, they had been dealing with quite a lot of problems with Group A strep as we’ve also seen it in Australia. And because that meant that they needed to use a lot of these first line antibiotics locally in the UK, it was less available to export to other places who also needed it like Australia.

00:18:10:11 - 00:18:39:02

Dr Brendan McMullan

So we are affected unfortunately by those global supply chains and right now we’re not in a position to manufacturer all of these antibiotics ourselves, although I think that is one of the important options to consider in terms of moving forward considering local capacity and supply chains. That’s obviously a question bigger than me. That’s something that needs to be considered really at a national and state level.

00:18:39:02 - 00:18:43:02

Dr Brendan McMullan

But I think that it is a really important issue to address.

00:18:43:04 - 00:18:58:24

Dr Lawrie Bott

Yes. So that was my next question. I was going to ask whether, in fact, there was a way to avoid this significant dependence we have on global supply. Is this an issue that’s being considered by other groups at the moment?

00:18:59:01 - 00:19:28:22

Dr Brendan McMullan

Well, look, to my knowledge, I think it’s certainly front of mind. It’s not just antibiotics, obviously, although these are really important drugs. But I think the pandemic and what happened to international travel also affected international supply. So I think it is front of mind for those dealing with drug regulation to consider supply chains and mechanisms for distributed production or potentially local production of antibiotics.

00:19:28:22 - 00:19:45:15

Dr Brendan McMullan

But, like I said, these are these are big picture comments that are above my above my pay grade, but certainly worth talking about the impact that we have seen in the community for prescribers and pharmacies and for children and families.

00:19:45:17 - 00:20:00:00

Dr Lawrie Bott

So, Brendan, antibiotic resistance is such an important and challenging area and it’s obviously a growing public health threat. Can you explain more about antibiotic resistance and what needs to be done?

00:20:00:02 - 00:20:37:18

Dr Brendan McMullan

Yeah, antibiotic resistance is really one of the crucial – I think it’s not too much of an exaggeration to say – existential crises of our time. So we rely on antibiotics, effective antibiotics to basically safely conduct, you know, much of modern medicine. So we need effective antibiotics to deliver safe maternity care, neonatal care, surgery, intensive care, chemotherapy and transplant. You know, many, many areas and antimicrobial resistance absolutely threatens that.

00:20:37:23 - 00:21:15:18

Dr Brendan McMullan

And it is just getting worse. So, it’s unfortunately a predictable consequence of use of antimicrobials. To some extent, it’s unavoidable because these bacteria and other organisms will evolutionarily compete with each other and try to find ways around anything we do to control them. So, this, you know, explains the phenomenon of antimicrobial resistance. Some parts of the world face major challenges with antimicrobial resistance in their routine parts of their hospital and community care.

00:21:15:18 - 00:21:46:07

Dr Brendan McMullan

So, for example, not having effective drugs to treat the majority of their neonatal infections or for people in intensive care. In Australia, we have been in some ways relatively better status from a global perspective in terms of the amount and severity of antimicrobial resistance. But, even here, we are facing increasing challenges. So, as a couple of examples, Gram-negative resistance.

00:21:46:07 - 00:22:26:18

Dr Brendan McMullan

So, extended spectrum beta lactamase produces, among E coli and other Gram negatives are increasing both in hospitals and in the community, and we’re now seeing even more worrying resistance on the rise, such as carbapenemase-producing Enterobacterales or CPE, sometimes called CRE [carbapenem-resistant Enterobacteriaceae]. These are resistant to our sort of last line antibiotics, and although we do have usually antimicrobials available to treat those, they are often more toxic or more difficult to use or less available.

00:22:26:20 - 00:23:08:05

Dr Brendan McMullan

And so they may be started later in the person’s infection, obviously allowing that infection to progress before effective therapy is started. So, it’s a really big problem. And, Australia also, even among Gram positives, Australia has some of the highest rates of vancomycin resistant Enterococcus faecium in the world as well. So, we are seeing increasing resistance on all fronts and I think, you know, pathologists can provide a really important role, you know, microbiologists and other doctors by ensuring that there is that combination of diagnostic stewardship and antimicrobial stewardship.

00:23:08:05 - 00:23:36:15

Dr Brendan McMullan

So, you know, collecting the right test at the right time, providing those results in a timely and appropriate manner, cascade reporting of antimicrobials that are sensible and in line with the Royal College of Pathologists of Australasia guidelines. So, for example, you know, for a standard ampicillin or susceptible E coli not reporting that last line antibiotic results as part of your routine results when you see that susceptible E coli come up in that community urine sample.

00:23:36:15 - 00:23:59:13

Dr Brendan McMullan

And I know that is a lot of work right now. So, the RCPA has already done some standardisation about antibiogram reporting for hospitals, for example. And I know there’s some ongoing work to sort of ensure that those kind of quality control measures that really help with limiting resistance are undertaken.

00:23:59:13 - 00:24:26:14

Dr Brendan McMullan

This is a distributed responsibility that everyone wants to treat the infection in front of them, but at the same time we need to ensure that we’re treating that with the most targeted therapy that’s appropriate at the time, avoiding that broad spectrum, unnecessary therapy or therapy of an extended duration, if that’s unnecessary, because those are those are two important things that potentially contribute to antimicrobial resistance.

00:24:26:16 - 00:24:45:15

Dr Lawrie Bott

Yes. I mean, as you mentioned, it’s evolution at work or at play and our future is dependent on staying ahead of the bugs. Okay. So back to children and what needs to be done differently regarding antibiotic use in children?

00:24:45:17 - 00:25:19:11

Dr Brendan McMullan

Yeah. So, I think some of this is really going back to basics and, you know, education, communication, review. So, I think we, as practitioners, and the public need to educate ourselves about common infections in children, about viruses and bacteria, and about what’s needed if we’re giving them antibiotics in terms of body size and dosing, swallowing and formulation, appropriate sort of clinical progression and review.

00:25:19:13 - 00:25:50:17

Dr Brendan McMullan

And, if we find ourselves in a position where we’re not sure what to do, you know, phone a friend or seek advice from an appropriate person who has the knowledge or expertise to provide that advice. I think we need to communicate with each other – that’s pathologists, that’s prescribers, that’s members of the public – in terms of providing appropriate antimicrobial advice for the infection of interest, taking into account paediatric considerations.

00:25:50:19 - 00:26:20:11

Dr Brendan McMullan

So, for example, finding a Group B strep result in a newborn has a very different significance from finding that in a 12-year-old or a 25-year-old, potentially. And I think those of us who provide care to children need to sort of understand the sort of common infections and common progression of illness or at least be working in partnership with people who do that. Children, as I said, get lots of infections, especially in the first few years of life.

00:26:20:13 - 00:26:42:07

Dr Brendan McMullan

The nice thing is they generally respond to them very well, so they will get sick and it’s very unpleasant for them and their caregivers. If you’ve ever had to look after a toddler who is unwell, but for the most part, you know, with appropriate supportive care and with additional therapy, if needed, they will bounce back and be healthy and happy again.

00:26:42:09 - 00:27:04:15

Dr Lawrie Bott

So, this is an area of such great importance and of great interest. Antibiotics is clearly a key area in now health, whatever age you are. Thank you for helping us understand it. We’ve been talking to Brendan McMullan on the Pathologists Cut. Thank you for talking with us today, Brendan.

00:27:04:17 - 00:27:06:08

Dr Brendan McMullan

Thanks very much, Lawrie.

00:27:06:10 - 00:27:17:16

Voiceover

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