Ceftolozane/tazobactam disrupts Pseudomonas aeruginosa biofilms under static and dynamic conditions.

Background: Pseudomonas aeruginosa biofilms limit the efficacy of currently available antibacterial therapies and pose significant clinical challenges. Pseudomonal biofilms are complicated further when other markers of persistence such as mucoid and hypermutable phenotypes are present. There is currently a paucity of data regarding the activity of the newer β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam against P.

Changes in isolation guidelines for CPE patients results in only mild reduction in required hospital beds.

Background: Carbapenemase-producing Enterobacterales (CPE) are an emerging public health concern globally as they are resistant to a broad spectrum of antibiotics. Colonisation with CPE typically requires patients to be managed under 'contact precautions', which creates additional physical bed demands in healthcare facilities.

Methods: This study examined the potential impact of revised isolation guidelines introduced in late 2023 in Victoria, Australia, that relaxed the requirement for indefinite isolation of CPE-colonised patients in contact precautions, based on admission of CPE-diagnosed cases prior to the guideline change.

A Multimodal Spectroscopic Approach Combining Mid-infrared and Near-infrared for Discriminating Gram-positive and Gram-negative Bacteria.

The rapid and accurate identification of pathogenic bacteria is crucial for combating the growing threat of antibiotic resistance, nosocomial infections, and food safety concerns. This study presents a novel and comprehensive comparison of two vibrational spectroscopic techniques - attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and a low-cost miniature near-infrared (NIR) spectrometer - for distinguishing Gram-positive and Gram-negative bacterial samples grown using the same stock media solution. This is the first report of NIR spectroscopy being applied to differentiate Gram-positive and Gram-negative bacteria, as well as the first direct comparison of ATR-FTIR and NIR for the combined multimodal analysis of clinical bacterial isolates.

Environmental microbiome, human fungal pathogens, and antimicrobial resistance.

Traditionally, antifungal resistance (AFR) has received much less attention compared with bacterial resistance to antibiotics. However, global changes, pandemics, and emerging new fungal infections have highlighted global health consequences of AFR. The recent report of the World Health Organisation (WHO) has identified fungal priority pathogens, and recognised AFR among the greatest global health threats.

Fatty Acid Uptake in and the Landscape of Its Infectious Niches.

is consistently ranked among the most problematic multidrug-resistant bacterial pathogens in healthcare systems. Developing novel treatments requires a better understanding of its interaction with the host environment. Although bacteria can synthesize fatty acids, emerging findings suggest a potential preference for their acquisition from the host.

Predicting drug resistance using artificial intelligence and clinical MALDI-TOF mass spectra.

Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is widely used in clinical microbiology laboratories for bacterial identification but its use for detection of antimicrobial resistance (AMR) remains limited. Here, we used MALDI-TOF MS with artificial intelligence (AI) approaches to successfully predict AMR in , a priority pathogen with complex AMR mechanisms. The highest performance was achieved for modern β-lactam/β-lactamase inhibitor drugs, namely, ceftazidime/avibactam and ceftolozane/tazobactam.

Carbapenemase-producing enterobacterales colonisation status does not lead to more frequent admissions: a linked patient study.

Background: Hospitals in any given region can be considered as part of a network, where facilities are connected to one another - and hospital pathogens potentially spread - through the movement of patients between them. We sought to describe the hospital admission patterns of patients known to be colonised with carbapenemase-producing Enterobacterales (CPE), and compare them with CPE-negative patient cohorts, matched on comorbidity information.

Methods: We performed a linkage study in Victoria, Australia, including datasets with notifiable diseases (CPE notifications) and hospital admissions (admission dates and diagnostic codes) for the period 2011 to 2020.

The effect of opting-in versus opting-out forming on the rate of reported variants of questionable significance in prenatal microarray.

Objective: To examine the effect of patient-selected opt-in versus opt-out option on the rate of reported variants of uncertain clinical significance (VOUS) and high-frequency low-penetrant (HFLP) findings in prenatal microarray testing.

Methods: A standard microarray consent form in Israel includes a requirement to note patient choice to be or not to be informed about the presence of VOUS and HFLP variants. The original form was designed as an opting-out method, in which the women had to actively mark if they did not want to be informed about questionable findings.

A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution.

To fully understand how the human brain works, knowledge of its structure at high resolution is needed. Presented here is a computationally intensive reconstruction of the ultrastructure of a cubic millimeter of human temporal cortex that was surgically removed to gain access to an underlying epileptic focus. It contains about 57,000 cells, about 230 millimeters of blood vessels, and about 150 million synapses and comprises 1.

Lactate metabolism promotes in vivo fitness during Acinetobacter baumannii infection.

Acinetobacter baumannii is one of the most prevalent causes of nosocomial infections worldwide. However, a paucity of information exists regarding the connection between metabolic capacity and in vivo bacterial fitness. Elevated lactate is a key marker of severe sepsis.

Seeing is believing: Correlating optoelectronic functionality with atomic scale imaging of single semiconductor nanocrystals.

A unique on-chip method for the direct correlation of optical properties, with atomic-scale chemical-structural characteristics for a single quantum dot (QD), is developed and utilized in various examples. This is based on performing single QD optical characterization on a modified glass substrate, followed by the extraction of the relevant region of interest by focused-ion-beam-scanning electron microscope processing into a lamella for high resolution scanning transmission electron microscopy (STEM) characterization with atomic scale resolution. The direct correlation of the optical response under an electric field with STEM analysis of the same particle allows addressing several single particle phenomena: first, the direct correlation of single QD photoluminescence (PL) polarization and its response to the external field with the QD crystal lattice alignment, so far inferred indirectly; second, the identification of unique yet rare few-QD assemblies, correlated directly with their special spectroscopic optical characteristics, serving as a guide for future designed assemblies; and third, the study on the effect of metal island growth on the PL behavior of hybrid semiconductor-metal nanoparticles, with relevance for their possible functionality in photocatalysis.

Multi-Locus Microsatellite Typing of Colonising and Invasive Isolates from Patients Post Lung Transplantation and with Chronic Lung Disease.

can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of infection, but little is known about the contribution of different strains to the development of different phenotypes and CLAD.

Genomic investigation of multispecies and multivariant outbreak reveals key role of horizontal plasmid transmission.

Objectives: New Delhi metallo-β-lactamases (NDMs) are major contributors to the spread of carbapenem resistance globally. In Australia, NDMs were previously associated with international travel, but from 2019 we noted increasing incidence of NDM-positive clinical isolates. We investigated the clinical and genomic epidemiology of NDM carriage at a tertiary-care Australian hospital from 2016 to 2021.

Clinical and economic impact of ventricular assist device infections: a real-world claims analysis.

Background: VAD therapy has revolutionized the treatment of end-stage heart failure, but infections remain an important complication. The objective of this study was to characterize the clinical and economic impacts of VAD-specific infections.

Methods: A retrospective analysis of a United States claims database identified members ≥ 18 years with a claim for a VAD implant procedure, at least 6 months of pre-implant baseline data, and 12 months of follow-up between 1 June 2016 and 31 December 2019.

Implementation Strategies Addressing Stakeholder-Perceived Barriers and Enablers to the Establishment of a Beta-Lactam Antibiotic Therapeutic Drug Monitoring Program: A Qualitative Analysis.

Background: Therapeutic drug monitoring (TDM) of beta-lactam antibiotics (beta-lactams) is increasingly recommended for optimizing antibiotic exposure in intensive care patients with sepsis. However, limited data are available on the implementation of beta-lactam TDM in complex health care settings. Theory-based approaches were used to systematically explore barriers and enablers perceived by key stakeholders in the implementation of beta-lactam TDM in the intensive care unit.

PmxPred: A data-driven approach for the identification of active polymyxin analogues against gram-negative bacteria.

The multidrug-resistant Gram-negative bacteria has evolved into a worldwide threat to human health; over recent decades, polymyxins have re-emerged in clinical practice due to their high activity against multidrug-resistant bacteria. Nevertheless, the nephrotoxicity and neurotoxicity of polymyxins seriously hinder their practical use in the clinic. Based on the quantitative structure-activity relationship (QSAR), analogue design is an efficient strategy for discovering biologically active compounds with fewer adverse effects.

Virulence attributes of successful methicillin-resistant lineages.

Methicillin-resistant (MRSA) is a leading cause of severe and often fatal infections. MRSA epidemics have occurred in waves, whereby a previously successful lineage has been replaced by a more fit and better adapted lineage. Selection pressures in both hospital and community settings are not uniform across the globe, which has resulted in geographically distinct epidemiology.

causes recurrent vulvovaginal candidiasis by forming morphologically disparate biofilms on the human vaginal epithelium.

Background: Recurrent vulvovaginal candidiasis (RVVC) is a recalcitrant medical condition that affects many women of reproductive age. The importance of biofilm formation by in RVVC has been recently questioned. This study aimed to elucidate the fundamental growth modes of in the vagina of patients with RVVC or sporadic vulvovaginal candidiasis (VVC) and to assess their roles in the persistence of RVVC.

EHR-QC: A streamlined pipeline for automated electronic health records standardisation and preprocessing to predict clinical outcomes.

The adoption of electronic health records (EHRs) has created opportunities to analyse historical data for predicting clinical outcomes and improving patient care. However, non-standardised data representations and anomalies pose major challenges to the use of EHRs in digital health research. To address these challenges, we have developed EHR-QC, a tool comprising two modules: the data standardisation module and the preprocessing module.

A genomic survey of isolates from hospitalized patients in Melbourne, Australia.

There has been a decrease in healthcare-associated infection in Australia, but an increase in the genetic diversity of infecting strains, and an increase in community-associated cases. Here, we studied the genetic relatedness of isolated from patients at a major hospital in Melbourne, Australia. Diverse ribotypes were detected, including those associated with community and environmental sources.