Antimicrobials
Antimicrobials, which include antibiotics, antivirals, antifungals and antiparasitic medications, are the most frequently prescribed medications in children.
Unfortunately, there is clear inequity in access to effective antimicrobial treatment in children compared with adults. This leads to worse clinical outcomes (morbidity) and death (mortality) from infection, with ineffective treatment also driving antibiotic resistance.
To tackle these issues, our antimicrobial research aims to facilitate interdisciplinary collaborations to:
- Conduct rigorous clinical trials of therapeutics in children
- Improve the safety, efficacy and accessibility of treatment using pharmacometrics
- Utilise genomics and digital health to personalise medication use for children
- Collect data on off-label medication use in children to inform future safer prescribing practices
Group Leaders
Group Members
Our projects
Clinical Drug Trials
BEST Trial
The BEST Trial aims to determine whether treatment of bone and joint infections in children with oral antibiotics alone is just as effective as treatment with intravenous antibiotics followed by an oral antibiotic course.
Read more...ITCHY- Ivermectin Therapy in CHildren under 5 Years of age
A multicentre, open-label prospective pharmacokinetic study in Laos PDR aims to determine in young children (aged two to five years and weighing between 10 to 15 kilograms) if an ivermectin dose of 3 mg achieves comparable drug exposure to the recommended dose in older children. We will also determine whether this dose is safe and effective for the treatment of scabies infection in this age group.
SNAP – Staphylococcus aureus Network Adaptive Platform trial (SNAP)
A multicentre, open-label randomised adaptive trial that aims to identify the effect of a range of clinical interventions on all-cause 90-day mortality in patients with Staphylococcus aureus bloodstream infection (SAB).
FosUTI – FOSfomycin Versus Standard of Care in Children with Antibiotic-Resistant Urinary Tract Infections
A multi-centre non-inferiority, pragmatic, adaptive trial to evaluate the safety, tolerability, efficacy and pharmacokinetics of oral fosfomycin in children with antibiotic-resistant urinary tract infections.
ID-MAGIC – Individualised Dose optiMisAtion of Ganciclovir in Immunocompromised Children
A randomised, unblinded, adaptive trial of optimised antiviral dosing for cytomegalovirus (CMV) viraemia in immunocompromised children that aims to determine if individualised dosing of IV ganciclovir is superior to standard IV ganciclovir dosing in reducing the time of virological response.
Pharmacokinetic (PK) and Pharmacodynamic (PD) audit and observational studies
O-SNAP – Optimising antibiotic dosing in the Staphylococcus aureus Network Adaptive Platform trial
A multi-centre pharmacokinetic-pharmacodynamic (PKPD) sub-study embedded in the SNAP trial aims to compare the difference in treatment success at day 90, between patients receiving treatment with a β-lactam antibiotic for methicillin-sensitive S. aureus bacteraemia who have achieved a conventional PKPD target, versus those that have not achieved the PKPD target.
Optimising antibiotic dosing children with bacteremia
A prospective observational study that aims to determine the pharmacodynamic target of commonly used antibiotics in children with bacteraemia due to Staphylococcus aureus, Streptococcus pneumoniae, E. coli, Group A Streptococcus or Pseudomonas aeruginosa.
Determining antimicrobial pharmacokinetics and pharmacodynamics in young infants
A prospective observational study that aims to determine the pharmacokinetics and pharmacodynamics of antimicrobials in young infants aged zero to 120 days admitted to the neonatal intensive care unit at The Royal Children's Hospital.
Advancing the evidence base for off-label medications in children
A multicentre prospective audit that aims to determine dosing regimens used as well as the safety and efficacy of off-label medications in children up to 18 years of age admitted to the participating paediatric hospitals. This study will also determine the population PK of off-label medications used in children aged up to 18 years.
ATOMIC – Alternative therapeutic drug monitoring and dose optimisation in immunosuppressed paediatric patients
A prospective observational cohort study that aims to determine in paediatric oncology and bone marrow transplant patients the pharmacokinetics of antifungals and immunosuppressants.
VANC APP – Assessing Precise dosing and Prompt drug monitoring to improve the attainment of target concentrations
A multisite prospective cohort study to determine the proportion of young infants achieving target trough vancomycin concentrations at the first steady-state level when using a model-based dosing regimen and the proportion of those when model-based dosing is used followed by therapeutic drug monitoring (TDM) and dose adjustment after the first dose.
DOSE CF Kids – opportunistic pharmacokinetic-pharmacodynamic sub-study of the BEAT CF Pulmonary Exacerbations Cohort
Prospective PKPD study nested in the BEAT CF (Bayesian Evidence Adaptive Treatment of Cystic Fibrosis) trial which aims to characterise the PKPD of intravenous antibiotics used for the treatment of pulmonary exacerbations in children with cystic fibrosis. This will inform optimal antibiotic dosing.
Research studies on adverse drug reactions
A Stratified Automated Allergy Assessment Risk Tool (SMAART) embedded in the electronic medical record to de-label children with antibiotic allergies
A multicentre prospective audit of a clinical decision support intervention – an automated tool built in the hospital Electronic Medical Record (EMR) – to improve the risk stratification, assessment, and de-labelling of children with an antibiotic allergy label.
Network projects
Australasian Kids Dose Consortium
A network of paediatric clinician researchers from tertiary hospitals across Australia and New Zealand was established to serve as a dedicated platform for the research of therapeutics for the most common diseases of childhood. This consortium will bolster the capacity and capability to rapidly implement paediatric trials of therapeutics in the face of emerging health threats.
Funding
- National Health and Medical Research Council (NHMRC)
- Medical Research Future Fund (MRFF)
- Thrasher Research Fund
- HCF Research Foundation
- Australasian Society of Infectious Diseases
- Avant Foundation Doctor in Training Research Scholarship
Collaborations
- Australasian Kids Dose Consortium
- Burnet Institute
- Certara
- Christchurch Hospital, New Zealand
- Fudan University, China
- Great Ormond Street Institute of Child Health, United Kingdom
- John Hunter Hospital
- Australasian Kids Dose Consortium
- Kidzfirst at Middlemore, New Zealand
- Lao Tropical and Public Health Institute
- Menzies School of Health Research
- Monash Children’s Hospital
- Monash University
- Pathology Queensland
- Perth Children’s Hospital
- The Royal Children’s Hospital
- Royal Darwin Hospital
- Royal Hobart Hospital
- Shenzhen Children’s Hospital, China
- South Australian Health and Medical Research Institute
- Starship Children’s Hospital, New Zealand
- Sydney Children’s Hospital, Randwick
- Sydney School of Public Health
- The Children’s Hospital at Westmead
- The Peter Doherty Institute For Infection and Immunity
- Telethon Kids Institute
- University of Auckland
- University of Melbourne
- University of Newcastle
- University of Otago
- University of Sydney
- University of Queensland
- Victorian Infectious Diseases Service
- Queensland Children’s Hospital
- Women’s and Children’s Hospital
Gwee A, Cranswick N, McMullan B, et al. Continuous Versus Intermittent Vancomycin Infusions in Infants: A Randomized Controlled trial. PEDIATRICS. 2019;143(2):e20182179. DOI:10.1542/peds.2018-2179
Wilkins AL, Lai T, Zhu X,..Gwee A. Individualized vancomycin dosing in infants: prospective evaluation of an online dose calculator. INT J ANTIMICROB AGENTS. 2023;61(3):106728. DOI:10.1016/j.ijantimicag.2023.106728
Gwee A, Autmizguine J, Curtis N, Duffull SB. Twice- and Thrice-daily Cephalexin Dosing for Staphylococcus aureus Infections in Children. Pediatr Infect Dis J. 2020 Jun;39(6):519-522. DOI:10.1097/INF.0000000000002646
Gwee A, Duffull SB, Daley AJ, et al. Identifying a therapeutic target for vancomycin against staphylococci in young infants. J ANTIMICROB CHEMOTHER. 2022;77(3):704-710. DOI:10.1093/jac/dkab469
Gwee A, Duffull S, Zhu X, Tong SYC, Cranswick N, McWhinney B, Ungerer J, Francis J, Steer AC. Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. PLoS Negl Trop Dis. 2020 Dec 7;14(12):e0008886. DOI:10.1371/journal.pntd.0008886