Antimicrobial Resistance in Enterobacterales, Acinetobacter spp. and Pseudomonas aeruginosa Isolates From Bloodstream Infections in Australian Children, 2013-2021.

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.

Australian Group on Antimicrobial Resistance surveillance outcome programs - bloodstream infections and antimicrobial resistance patterns from patients less than 18 years of age, January 2020 - December 2021.

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.

Safety and tolerability of bronchoscopic and nebulised administration of bacteriophage.

Introduction: Pseudomonas aeruginosa is an organism well known for causing significant morbidity and mortality in people living with chronic lung conditions such as cystic fibrosis. We describe the safety, tolerability, and potential efficacy of bronchoscopic and nebulised bacteriophage administration, offering insights into a potential breakthrough for the treatment of chronic infections particularly in children and adolescents.

Method: A 12-year-old female (F12) and a 17-year-old male (M17), both diagnosed with cystic fibrosis and chronic P.

Using a human colonoid-derived monolayer to study bacteriophage translocation.

Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation , we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment .

Host transcriptomics and machine learning for secondary bacterial infections in patients with COVID-19: a prospective, observational cohort study.

Background: Viral respiratory tract infections are frequently complicated by secondary bacterial infections. This study aimed to use machine learning to predict the risk of bacterial superinfection in SARS-CoV-2-positive individuals.

Methods: In this prospective, multicentre, observational cohort study done in nine centres in six countries (Australia, Indonesia, Singapore, Italy, Czechia, and France) blood samples and RNA sequencing were used to develop a robust model of predicting secondary bacterial infections in the respiratory tract of patients with COVID-19.

Phage Therapy in Korea: A Prescribers' Survey of Attitudes Amongst Korean Infectious Diseases Specialists Towards Phage Therapy.

Background: Concerns about the rise in antimicrobial resistance have led to renewed interest in phage therapy worldwide, but perceptions among relevant medical professionals in Korea remain largely unknown.

Materials And Methods: We conducted a semi-quantitative online survey to evaluate the Korean infectious disease specialists' perception of phage therapy.

Results: We sent out the link to the questionnaire to 380 subjects and received 91 replies, with 90/91 respondents identifying as Korean infectious diseases specialists or trainees.

Australian Group on Antimicrobial Resistance (AGAR) Australian Gram-negative Surveillance Outcome Program (GnSOP) Bloodstream Infection Annual Report 2022.

The Australian Group on Antimicrobial Resistance (AGAR) performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric gram-negative pathogens. The 2022 survey was the tenth year to focus on blood stream infections caused by Enterobacterales, and the eighth year where Pseudomonas aeruginosa and Acinetobacter species were included. Fifty-five hospitals Australia-wide participated in 2022.

Quantifying the Economic and Clinical Value of Reducing Antimicrobial Resistance in Gram-negative Pathogens Causing Hospital-Acquired Infections in Australia.

Introduction: Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making.

Translating phage therapy into the clinic: Recent accomplishments but continuing challenges.

Phage therapy is a medical form of biological control of bacterial infections, one that uses naturally occurring viruses, called bacteriophages or phages, as antibacterial agents. Pioneered over 100 years ago, phage therapy nonetheless is currently experiencing a resurgence in interest, with growing numbers of clinical case studies being published. This renewed enthusiasm is due in large part to phage therapy holding promise for providing safe and effective cures for bacterial infections that traditional antibiotics acting alone have been unable to clear.

A Streamlined Approach for Fluorescence Labelling of Low-Copy-Number Plasmids for Determination of Conjugation Frequency by Flow Cytometry.

Bacterial conjugation plays a major role in the dissemination of antibiotic resistance and virulence traits through horizontal transfer of plasmids. Robust measurement of conjugation frequency of plasmids between bacterial strains and species is therefore important for understanding the transfer dynamics and epidemiology of conjugative plasmids. In this study, we present a streamlined experimental approach for fluorescence labelling of low-copy-number conjugative plasmids that allows plasmid transfer frequency during filter mating to be measured by flow cytometry.

The evolution and international spread of extensively drug resistant Shigella sonnei.

Shigella sonnei causes shigellosis, a severe gastrointestinal illness that is sexually transmissible among men who have sex with men (MSM). Multidrug resistance in S. sonnei is common including against World Health Organisation recommended treatment options, azithromycin, and ciprofloxacin.

Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria.

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20-40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection.

Pathway and Network Analyses Identify Growth Factor Signaling and MMP9 as Potential Mediators of Mitochondrial Dysfunction in Severe COVID-19.

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes.

Blood transcriptome responses in patients correlate with severity of COVID-19 disease.

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected individuals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state.

Pharmacokinetics/pharmacodynamics of phage therapy: a major hurdle to clinical translation.

Background: The increasing emergence of antimicrobial resistance worldwide has led to renewed interest in phage therapy. Unlike antibiotics, the lack of pharmacokinetics/pharmacodynamics (PK/PD) information represents a major challenge for phage therapy. As therapeutic phages are biological entities with the ability to self-replicate in the presence of susceptible bacteria, their PK/PD is far more complicated than that of antibiotics.

transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study.

Purpose: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients.

Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial.

Introduction: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.

Methods And Analysis: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia's Therapeutic Goods Administration Special Access Scheme.

Chest CT in COVID-19 patients: A clinical need.

Introduction: The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has resulted in a global healthcare crisis. The provision of computed tomography (CT) imaging services by radiology departments for COVID-19 patients poses multiple challenges. Consequently, it is important to explore the clinical need and indications for thoracic CT and whether they subsequently alter patient management.