International Network of Antibiotic Allergy Nations (iNAAN): Protocol for a type 2 hybrid effectiveness-implementation multicentre prospective cohort and target trial emulation study evaluating penicillin allergy delabeling via direct oral challenge.

Background: Penicillin allergies are reported in 1 in 10 hospitalised patients globally and are associated with inferior patient and health service outcomes. However, more than 95% of low-risk penicillin allergies can be removed by direct oral challenge (DOC).

Objective: The International Network of Antibiotic Allergy Nations (iNAAN) aims to evaluate the utility of an audit and feedback (A&F) and education implementation strategy to increase the adoption of penicillin DOC in patients with a low-risk penicillin allergy, while concurrently assessing the impact of penicillin DOC on antibiotic prescribing and health service outcomes.

Antibiotic therapy for severe bacterial infections.

Background: Early antibiotic therapy for patients with severe infections is essential to improve outcomes. Conversely, use of overly broad antibiotic therapy for susceptible pathogens or unnecessary antibiotics in patients without bacterial infections is associated with adverse life-threatening events and superinfections. Antibiotics-induced changes in the human microbiota alter both immune and metabolic systems.

Implementation of outpatient parenteral antimicrobial therapy program in the contemporary health care system: A narrative review of the evidence.

Outpatient parenteral antimicrobial therapy (OPAT) program has become an established clinical practice globally, though its implementation varies across jurisdictions. This review explores the implementation of OPAT within contemporary healthcare systems. OPAT services are organised centrally or decentrally within healthcare systems or integrated into hospital-at-home programs.

Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease, and current pharmacological therapies are directed toward the management of electrical manifestations. To date, none address the underlying pathophysiology of this progressive condition. We evaluated the therapeutic efficacy of Tideglusib (TD) in Ank2 cardio-selective-knockout and homozygous desmoglein-2 mutant ACM mouse models.

Continuous or extended vs intermittent infusions of beta-lactam antibiotics in ICU patients with pneumonia: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) of intensive care unit (ICU) patients with pneumonia was conducted to compare the clinical outcomes of beta-lactam antibiotics when administered by prolonged infusion vs intermittent infusion. The systematic search was conducted in Medline (via PubMed), CINAHL, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov.

Development of blood culture time-to-positivity as a pharmacodynamic indicator for monitoring antibiotic therapy against MDR Gram-negative bacteria.

Objectives: We investigated the use of time-to-positivity (Tpos), a readily available parameter measured from automated blood culture incubators, as a surrogate marker for serum antimicrobial activity during antibiotic treatment against ESBL- and carbapenemase-producing Klebsiella pneumoniae.

Methods: Banked human serum spiked with clinically representative concentrations of different antibiotics was injected into aerobic blood culture bottles containing 1 × 104 mL inoculum of K. pneumoniae isolates.

Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy.

Purpose: Optimal dosing of meropenem and piperacillin/tazobactam in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to variable pharmacokinetics. We aimed to develop generalisable optimised dosing recommendations for these antibiotics.

Methods: Prospective, multinational pharmacokinetic study including patients requiring various forms of RRT.

The contribution of truncating variants to human cardiomyopathy.

Background: Genetic diagnosis has become increasingly important to guide clinical decision making for patients with dilated cardiomyopathy (DCM). Disease-causing (P/LP) missense variants in the gene cause a highly penetrant arrhythmogenic dilated cardiomyopathy (DCM), but the role of truncating variants ( ) is unclear.

Objective: Assess the contribution of to DCM.

Spectroscopic Characterization and Differentiation of SARS-CoV-2 Virus-like Particles.

Virus-like particles (VLPs) are recombinant, noninfectious, self-assembled structures that are made up of the viral structural proteins that mimic the morphology of viruses but lack genomic material. VLPs have been used to develop vaccines against viruses and cancer, leading to a surge of industry interest in exploring VLP vaccines. There are strict quality controls as a part of downstream processing in the production of nonreplicating VLPs.

The changing epidemiology of species in Asia Pacific and evidence for optimizing antifungal dosing in challenging clinical scenarios.

Introduction: The global burden of invasive fungal infections (IFIs) is increasing, with the threat of disease exacerbated by the emergence of antifungal resistance. While antifungals remain the mainstay for the treatment of IFIs, there is a growing recognition of the many patient variables, particularly in challenging situations (e.g.

Pharmacological Research Agenda on Adult Extracorporeal Membrane Oxygenation Using the Delphi Method: A Position Article of the Extracorporeal Membrane Oxygenation Pharmacology Network.

Objectives: Extracorporeal membrane oxygenation (ECMO) is a critical intervention for patients with severe cardiac or respiratory failure. However, pharmacological management for ECMO-supported patients presents unique challenges due to alterations in drug pharmacokinetics and pharmacodynamics induced by the ECMO circuit and underlying critical illness. This position paper identifies key research priorities in ECMO pharmacology using a structured Delphi consensus process and provides a focused review of current evidence and knowledge gaps to inform future research and clinical practice.

Marginal cytokine modulation by Schistosoma mansoni soluble egg antigen in SARS-CoV-2-infected K18-hACE2 mice.

Herein, we explore the potential influence of Schistosoma mansoni Sambon, 1907 soluble egg antigen (SmSEA) on the immunopathology of COVID-19 in K18-hACE2 mice infected with an Omicron BA.5 isolate of SARS-CoV-2. SmSEA treatment was delivered in a single dose by intraperitoneal injection, shortly after intrapulmonary inoculation of SARS-CoV-2.

Cause and effect? A review of the impact of antibiotics on the gut microbiome in patients undergoing hematopoietic stem cell transplantation.

Introduction: Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk of infection due to immunosuppression, prompting routine use of prophylactic and broad-spectrum antibiotics for treatment. However, emerging evidence suggests that gut microbiome disruption (dysbiosis), partly caused by antibiotic use, is associated with poorer transplant outcomes, including graft-versus-host disease (GVHD), infection, and mortality.

Areas Covered: This narrative review discusses antibiotic use to prevent and treat febrile neutropenia in allo-HSCT recipients, including effectiveness, impacts on microbiome and GVHD, antimicrobial resistance and infection (CDI).

Seasonal variation of trifluoroacetic acid (TFA) in Antarctic ice cores analysed by direct injection non-suppressed ion chromatography-mass spectrometry (nsIC-MS).

This study presents the first record of trifluoroacetic acid (TFA) in Antarctic ice cores, offering valuable data on TFA and its precursors' long-range atmospheric transport and deposition in remote polar regions. TFA is an ultra-short chain perfluoroalkyl acid (PFAA) that has gained attention due to its environmental persistence, stability, and mobility. It is primarily formed as an end product of atmospheric degradation of halogenated refrigerants and blowing agents, particularly hydrofluorocarbons (HFCs) and unsaturated HFCs (u-HFCs).

A global survey of diagnostic practices in prosthetic joint infections.

Prosthetic joint infections (PJIs) lead to significant morbidity, mortality and healthcare costs. A timely and accurate microbiological diagnosis is crucial for administering appropriate antimicrobial therapy. Periprosthetic tissue cultures are considered the 'gold standard' for microbiologically diagnosing PJIs.

Optimization of antimicrobial therapy in critically ill patients, What Clinicians and Searchers Must Know.

Effective sepsis treatment requires not only the timely administration of appropriate antimicrobials but also precise dosing to maximize patient survival in intensive care units (ICUs). However, the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics in critically ill patients differ significantly from those in the general population. Understanding these pathophysiological changes is essential for optimizing antibiotic therapy.

Current practices in outpatient parenteral antimicrobial therapy programmes: an international multi-centre survey.

Objectives: This study aimed to assess the current international practices of outpatient parenteral antimicrobial therapy (OPAT).

Methods: A multi-site cross-sectional study was conducted, using REDCap platform for survey distribution and data collection. Data analysis was performed in SPSS version 29.

The pharmacokinetics of antibiotics in patients with obesity: a systematic review and consensus guidelines for dose adjustments.

Obesity can cause physiological changes resulting in antibiotic pharmacokinetic alterations and suboptimal drug exposures. This systematic review aimed to summarise the available evidence on this topic and provide guidance for dose adjustment of antibiotics in adult (age ≥18 years) patients with obesity (BMI >30 kg/m). We searched PubMed, Embase, and CENTRAL databases to find relevant studies published between database inception and Dec 30, 2023.

Flecainide for the Treatment of Andersen-Tawil Syndrome.

Background: Andersen-Tawil syndrome type 1 (ATS1) is a rare arrhythmogenic disorder resulting from loss-of-function mutations in KCNJ2. Although the use of flecainide has been proposed to treat and prevent life-threatening arrhythmic events in ATS1, it has only been tested in small case series with limited follow-up. We performed a multicenter cohort study to determine the impact of flecainide on ATS.

Evaluation of the stability of tigecycline in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy.

Background: Tigecycline is increasingly being considered in outpatient parenteral antimicrobial therapy (OPAT) programmes given its spectrum of activity; however, stability data are lacking, necessitating further study.

Objective: To assess tigecycline stability in elastomeric infusers under OPAT conditions, following the UK Yellow Cover Document (YCD) stability testing guidelines.

Methods: Tigecycline was reconstituted with normal saline in Leventon Dosi-Fuser and Baxter-LV10 infusers at doses of 50, 100 and 200 mg in 240 mL.

Population pharmacokinetics of intravenous fosfomycin: dose optimization for critically ill patients with and without kidney replacement therapy.

We investigated the pharmacokinetics (PK) of intravenous fosfomycin in critically ill patients undergoing different types of kidney replacement therapy (KRT) to identify optimized dosing regimens for patient care. Four prospective, observational studies contributed data of critically ill patients with prolonged-intermittent KRT (PIKRT, =18), continuous KRT (CKRT, =15), or without KRT (=12) for population PK analysis. Subsequently, licensed daily dosages (12-24 g), varying estimated glomerular filtration rates (eGFR, 0-120 mL/min/1.

Population Pharmacokinetic Modelling of Remdesivir and Its Metabolite GS-441524 in Hospitalised Patients with COVID-19.

Background And Objectives: There are limited data testing whether the licensed dose of remdesivir and its active metabolite GS-441524 achieve target concentrations in hospitalised patients with confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of coronavirus disease-2019 (COVID-19). The objectives of this study were to describe the population pharmacokinetics of remdesivir and GS-441524 in hospitalised patients treated for COVID-19 and develop a model to inform dose optimisation in clinical use.

Methods: This was a prospective, open-labelled, multi-centre, observational study in four Australian hospitals in adults with confirmed SARS-CoV-2 infection.

Correction of posaconazole concentrations for hypoalbuminemia.

Background: Posaconazole is an example of a highly protein-bound drug (>98%) in which therapeutic drug monitoring (TDM) is commonplace. Total drug concentration is typically measured, and in the setting of hypoalbuminemia, total concentrations are lower despite no anticipated change in unbound concentration. Data support that unbound posaconazole concentration is responsible for antifungal activity and, in theory, is responsible for adverse effects that are dose-related.

A Systematic Review of Pharmacokinetic Studies of Colistin and Polymyxin B in Adult Populations.

Background And Objective: The pharmacokinetics of polymyxins are highly variable and conventional dosing regimens may likely lead to sub-optimal exposures and outcomes, particularly in critically ill patients with multi-drug-resistant infections. The aim of this systematic review is to describe the published pharmacokinetic data and to investigate variables that have been shown to affect the pharmacokinetics of colistimethate sodium, colistin, and polymyxin B in adult populations.

Methods: Sixty studies were identified.

The FUSION Study: compatibility of antibiotics with commonly used medication infusions in a paediatric intensive care unit.

Objectives: Beta-lactams and vancomycin often require extended or continuous infusion strategies for antibiotic optimisation in the paediatric intensive care unit (PICU). Simultaneous administration of multiple drugs through a single lumen via a Y-site connector is utilised with uncertainty due to limited intravenous access and the common need for sedative-analgesic infusions in critical illness. The compatibility data supporting antibiotics and sedative-analgesics co-administration is lacking.