Publications by authors named "Phoebe Williams"

Despite widespread adoption of "high-dose" glucocorticoid definitions across international immunisation guidelines (i.e., prednisone-equivalent dosing >20 mg/day, or >2 mg/kg/day in children), the rationale remains unclear.

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Background: International consensus definitions for invasive aspergillosis (IA) in research are rigorous, yet clinically significant cases are often excluded from clinical studies for not meeting proven/probable IA case definitions. To better understand reasons for the failure to meet criteria for proven/probable infection, we herein review 47 such cases for their clinical and microbiological characteristics and outcomes.

Methods: Data on 47 cases that did not meet consensus IA definitions but were deemed significant were derived from a retrospective, observational, multicenter survey of 382 presumed IA cases across Australasia, of which findings of 221 proven/probable infections were recently published.

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Article Synopsis
  • Rising rates of antimicrobial resistance (AMR) were noted in Staphylococcus aureus and Enterococcus spp. in Australia, with a significant number of blood stream infections (BSIs) occurring in children.
  • The Australian Group on Antimicrobial Resistance (AGAR) analyzed 2,091 S. aureus and 534 enterococcal BSIs over nine years, revealing key trends in community vs. hospital onset infections and varying resistance levels.
  • A shift in resistance profiles was observed, especially in Enterococcus faecium, prompting the need for detailed and age-stratified reporting of AMR data.
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Background: Gram-negative bloodstream infections are associated with significant morbidity and mortality in children. Increasing antimicrobial resistance (AMR) is reported globally, yet efforts to track pediatric AMR at a national level over time are lacking.

Methods: The Australian Group on Antimicrobial Resistance (AGAR) surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia.

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Background: Antimicrobial resistance increasingly impacts paediatric mortality, particularly in resource-constrained settings. We aimed to evaluate the susceptibility profiles of bacteria causing infections in children from the Western Pacific region.

Methods: We conducted a systematic review and meta-analysis of bacteria responsible for common infections in children.

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  • Sepsis is a major cause of neonatal deaths, especially in low- and lower-middle-income countries (LLMIC), and the rise in antimicrobial resistance is changing the bacteria causing this issue.
  • A systematic review of 48 studies showed that gram-negative bacteria are now the leading cause of early-onset sepsis (EOS) and late-onset sepsis (LOS) worldwide, with different predominant pathogens found in LLMICs compared to high-income countries.
  • The findings suggest that current definitions for EOS and LOS are outdated, leading to ineffective antibiotic treatments, and call for standardizing definitions to improve global understanding and management of neonatal sepsis.
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From 1 January 2020 to 31 December 2021, thirty-eight institutions across Australia submitted data to the Australian Group on Antimicrobial Resistance (AGAR) from patients aged < 18 years (AGAR-Kids). Over the two years, 1,679 isolates were reported from 1,611 patients. This AGAR-Kids report aims to describe the population of children and adolescents with bacteraemia reported to AGAR and the proportion of resistant isolates.

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  • Respiratory syncytial virus (RSV) is a major cause of serious respiratory infections in young children, leading to many hospitalizations, but recent treatments like nirsevimab show promise in preventing these issues.
  • Nirsevimab, a monoclonal antibody, offers protection for at least 5 months and has been shown to significantly reduce hospital stays due to RSV in clinical trials and real-world data, with effectiveness rates ranging from 62.1% to 90%.
  • Successful implementation strategies for nirsevimab include seasonal administration for infants and contingency plans for those born before RSV season; however, careful consideration of cost and logistics is necessary for widespread usage.
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Background: In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data.

Methods: Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome.

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Article Synopsis
  • - Children and neonates are particularly vulnerable to antimicrobial resistance, making the development of suitable antibacterial agents for their use critical due to the existing barriers in research and development.
  • - In late 2022, WHO launched the first Paediatric Drug Optimisation (PADO) exercise focused on antibiotics, which aimed to identify and prioritize antibiotics for research and development that can address serious bacterial infections in children, especially in high-burden regions.
  • - The Review discusses the processes and outcomes of the PADO exercise, outlines follow-up actions for implementation, and emphasizes the importance of collaboration in improving access to essential medicines for children globally.
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Background: Mediastinal infections due to nontuberculous mycobacteria remain an exceedingly rare entity. Most cases in the published literature do not include pediatric patients. Due to their clinical infrequency, poor response to antimicrobial therapy and often precarious anatomical location, the optimal management of these lesions can be challenging.

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Background: High levels of antimicrobial resistance (AMR) are propagating deaths due to neonatal and paediatric infections globally. This is of particular concern in Southeast Asia and the Pacific, where healthcare resources are constrained and access to newer agents to treat multidrug-resistant pathogens is limited.

Methods: To assess the coverage provided by commonly prescribed empiric antibiotic regimens for children in low- and middle-income countries in Southeast Asia and the Pacific, we built a weighted incidence syndromic combination antibiogram (WISCA), parameterised using data obtained from a systematic review of published literature incorporating WHO-defined SEARO and WPRO regions in Ovid MEDLINE, EMBASE, Global Health and PubMed.

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  • The 2022 RSV epidemic in Sydney resulted in a significant increase in infections among infants, leading to high hospitalization rates and greater health impacts across various demographics.
  • Researchers analyzed the genomic sequences of RSV from 264 infants and assessed the immune response in women of childbearing age to identify contributing factors for the surge.
  • Findings indicated that the rise in cases was not linked to a new RSV strain or immune system changes due to the COVID-19 pandemic, highlighting the need for ongoing surveillance and research to combat RSV outbreaks and improve treatment strategies.
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Complex natural product functionalizations generally involve the use of highly engineered reagents, catalysts, or enzymes to react exclusively at a desired site through lowering of a select transition state energy. In this communication, we report a new, complementary strategy in which all transition states representing undesirable sites in a complex ionophore substrate are simultaneously energetically increased through the chelation of a metal ion to the large fragment we wish to neutralize. In the case of an electrophilic, radical based fluorination reaction, charge repulsion (electric field effects), induced steric effects, and electron withdrawal provide the necessary deactivation and proof of principle to afford a highly desirable natural product derivative.

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Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice.

Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017-December 2020). Descriptive analyses were used to report patients' demographics, predisposing factors, mycological characteristics, diagnosis and management.

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Background: Ventilator-associated pneumonia (VAP) caries a morbidity and mortality risk in the preterm neonate, particularly in the context of rising global antimicrobial resistance driving infections due to multidrug-resistant Gram-negative bacteria. Cefiderocol, a siderophilic cephalosporin, has broad Gram-negative antimicrobial activity and central nervous system penetration and is used for the treatment of hospital-acquired pneumonia or VAP in adults. Scarce data exists on its use in neonates.

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Article Synopsis
  • A global increase in invasive pneumococcal disease (IPD) among children has been observed, particularly in Australia after COVID-19 restrictions were eased.
  • The analysis highlights severe health impacts from IPD, even in vaccinated children without prior health issues.
  • Notably, nearly 50% of IPD cases were caused by serotypes not included in the 13-valent pneumococcal conjugate vaccine.
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Background: Urinary tract infections (UTIs) due to MDR organisms are increasingly common. The lack of paediatric data on efficacious antibiotics makes UTI treatment particularly challenging. Data on the efficacy of fosfomycin use for UTI in children are variable.

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  • Pneumonia remains a leading cause of hospitalization and mortality in young children globally, complicating antibiotic usage by making it challenging to differentiate between bacterial and non-bacterial pneumonia.
  • Researchers developed a causal Bayesian network (BN) by combining expert knowledge and data to predict pathogens responsible for childhood pneumonia, through collaboration with multiple domain experts via workshops and surveys.
  • The resulting BN model demonstrated promising performance, achieving an area under the receiver operating characteristic curve of 0.8 for predicting bacterial pneumonia, with 88% sensitivity and 66% specificity, while allowing for explainable predictions across various clinical variables related to pneumonia.
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The reality of human induced climate change is no longer in doubt, but the concerted global action required to address this existential crisis remains inexcusably inert. Together with climate change, biodiversity collapse is increasingly driving the emergence and spread of infectious diseases, the consequences of which are inequitable globally. Climate change is regressive in its nature, with those least responsible for destroying planetary health at greatest risk of suffering the direct and indirect health consequences.

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Infections remain a leading cause of death in neonates. The sparse antibiotic development pipeline and challenges in conducting neonatal research have resulted in few effective antibiotics being adequately studied to treat multidrug-resistant (MDR) infections in neonates, despite the increasing global mortality burden caused by antimicrobial resistance. Of 40 antibiotics approved for use in adults since 2000, only four have included dosing information for neonates in their labelling.

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The global spread of human monkeypox disease, a zoonotic infection related to smallpox and endemic to West and Central Africa, presents serious challenges for health systems. As of July 2022, 14 533 cases have been reported world-wide, leading to designation as a Public Health Emergency of International Concern. Monkeypox disease is spread from animals to humans through infected lesions or fluids; human-human transmission occurs through fomites, droplets or direct contact.

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