Children most at risk from antibiotic shortages

Global shortages of antibiotics are disproportionately affecting Australian children, write Tony Lai, Amanda Gwee, Brendan McMullan and Asha Bowen.

Antibiotics are among the most prescribed medications for Australian children.

A report by the Australian Commission on Safety and Quality in Health Care found that the highest rate of antibiotic dispensing for people under 65 years of age was to children aged two to four years.

However, several antibiotics have become increasingly difficult to obtain in recent months due to global shortages, namely supply chain and manufacturing issues exacerbated by the coronavirus 2019 (COVID-19) pandemic, according to the Therapeutic Goods Administration.

Compared with adults, these shortages disproportionately affect Australian children.

Which medications are difficult to obtain?

More recently, post-pandemic changes in disease epidemiology have led to increased group A Streptococcus (GAS) infections (eg, tonsillitis and scarlet fever) across the world.

As a result, the World Health Organization has recommended “continued close analysis of the epidemiological situation” across Europe.

This has further increased the demand for antibiotics.

Countries that manufacture antibiotics used for GAS infections have implemented export bans, resulting in many hospitals and pharmacies in Australia struggling to keep up with the increased demand.

Antibiotics affected by the shortage include cefalexin, amoxicillin, phenoxymethylpenicillin, amoxicillin–clavulanate and trimethoprim–sulfamethoxazole.

These shortages mainly affect the palatable syrup formulations that young children require for ease of administration.

Syrup formulations have far fewer brand substitutions available than tablets, hence the reason that restrictions further disadvantage children (here).

As a result, parents and health care providers find it challenging to access antibiotics needed to treat common childhood bacterial infections (eg, ear, urinary tract, skin and respiratory tract infections).

Moreover, the lack of timely and appropriate treatment for infections may lead to serious consequences (here and here).

Possible strategies

One strategy for managing antibiotic shortages is substituting the recommended first line antibiotic with an alternative antibiotic.

However, the evidence basis for this may be limited for some indications.

Potential disadvantages of this approach are the risk of additional side effects, lack of approval for that indication resulting in higher medication costs, absence of pharmacokinetic data to inform appropriate dosing, and different concentrations of formulations, which may contribute to the incorrect dispensing or administration of medications to children (here and here).

This can result in side effects from overdosing or lack of efficacy from underdosing.

Alternative antibiotics may also not be available in age-appropriate formulations (eg, an oral solution or suspension).

Although tablets can often, but not always, be crushed or capsules opened and mixed with food or drink (eg, apple purée), the result may be unpalatable, as the drug is very bitter and this taste is difficult to mask.

This may lead to unpredictable delivery of the correct dose or difficulties completing the treatment course (here).

In a worst-case scenario, where child-friendly oral formulations are unavailable, children may require admission to the hospital for intravenous antibiotics, putting pressure on already busy hospital departments.

The need for closer collaboration

Amid global shortages of antibiotics, real-time guidance for health care prescribers is needed on which antibiotics are currently available in community pharmacies, what is out of stock, and what the best available substitution is.

We argue that paediatricians, pharmacies, and the Australian Government need to work together to provide this updated guidance in real-time across the country.

The mechanisms for this beyond the children’s hospitals do not currently exist but are urgently needed.

Appropriately resourced committees should be assembled to provide real-time guidance for prescribers and dispensers of antibiotics for children across the country.

Digital innovations to address this would aid in delivering and communicating this information.

For example, the ability to interact digitally with prescribers to enable antibiotic substitution in real-time at the point of dispensing needs to be considered.

This will minimise the risk to children with an infection who cannot access the correct antibiotic type, formulation or dose.

Importantly, this will reduce the burden on families increasingly having to contact several pharmacies to source an appropriate antibiotic for their child.

Although local compounding of medications to improve palatability is an innovation that is expanding across Australia, compounding antibiotics at community pharmacies from tablets into liquids is cost prohibitive for most families, is not covered under the health care card benefits scheme for low income families, and is often not accessible in rural or resource-poor settings (here).

The need for the KIDS-DOSE Consortium

Clearly, further research and action are needed to ensure all children have access to age-appropriate, affordable antibiotic formulations with sufficient dosing and safety data.

Therefore, we have established the Australasian KIDS-DOSE Consortium, a network of paediatricians and pharmacists from 11 hospitals across Australia and New Zealand whose primary research agenda is to generate high quality evidence to ensure equity of access to antimicrobials in children so that all children can receive safe, effective treatment for their infections.

The Consortium will:

• collaborate to lead dedicated paediatric drug trials of novel and emerging therapeutics;
• collect dosing, pharmacokinetic and safety data on the off-label use of medications in children to inform safer future prescribing practices;
• advocate for equitable access to medications in children; and
• support translation of new evidence into clinical practice.

It is promising to see policies to address vulnerabilities in the international supply chain, such as the Australian Government’s $15 billion National Reconstruction Fund, but priority should be placed on antibiotics.

There is an over-reliance on only a few pharmaceutical wholesalers in Australia, and hospital formularies are restricted to contracted antibiotics brands.

We look forward to seeing the role of new GAS vaccines in decreasing the incidence of GAS infections and associated antibiotic use that will reduce demand.

Lastly, the community and health care providers should continue to raise awareness of antimicrobial resistance and the importance of responsible antibiotic use.

Tony Lai is an Antimicrobial Stewardship Pharmacist at Westmead Children’s Hospital in Sydney.

Associate Professor Amanda Gwee is a General Paediatrician, Infectious Diseases Physician and Clinical Pharmacologist at the Royal Children’s Hospital Melbourne; and Leader of the Antimicrobials Group at Murdoch Children’s Research Institute.

Dr Brendan McMullan is a Paediatric Infectious Diseases Physician and Microbiologist at Sydney Children’s Hospital, Randwick.

Associate Professor Asha Bowen is the Head of Skin Health at the Wesfarmers Centre of Vaccines and Infectious Diseases based at Telethon Kids Institute.

On behalf of the KIDS-DOSE Consortium.

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated. 

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