Publications by authors named "Schelenz S"

Background: Antifungal stewardship (AFS) is the judicious use of today's antifungal agents with the aim of improving patient outcomes and preserving their future effectiveness. Antifungal resistance (AFR) is increasing globally, with more patients at risk of Invasive Fungal Disease (IFD), highlighting the urgent need to standardize AFS practices in the UK. The aim of this position paper is to understand the current AFS landscape in the UK.

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Fungal infections are increasingly prevalent; however, antifungal stewardship attracts little funding or attention. Previous studies have shown that knowledge of guidelines and scientific evidence regarding antifungals is poor, leading to prescribing based on personal experiences and the inherent biases this entails. We carried out a retrospective study of inpatient antifungal usage at two major hospitals.

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In vitro screening of gallium-68(Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([Ga]Ga-ENT), considering different experimental factors.

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Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids.

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Introduction: Invasive fungal infections are a primary cause of morbidity and mortality in patients with haematological malignancies.

Case Presentation: We describe an unusual clinical and radiological presentation of invasive mucormycosis (IM) in a 69-year-old patient with relapsed acute myeloid leukaemia. The patient was diagnosed with disseminated IM with involvement of the central nervous system in an atypical location, lung, spleen, muscle, bone, and heart, after having completed induction and bridging chemotherapy to allogeneic haematopoietic stem cell transplant (HSCT).

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Gallium-68-labeled siderophores as radiotracers have gained interest for the development of infection-specific imaging diagnostics. Here, we report radiolabeling, screening, and pharmacokinetics (PK) of gallium-68-labeled schizokinen ([Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity.

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The emergent fungal pathogen is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries.

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Article Synopsis
  • CAPA, or COVID-19-associated pulmonary aspergillosis, occurs in patients with severe SARS-CoV-2 infections and has a high mortality rate of about 50%, complicated by azole resistance.
  • A genomic analysis of 21 CAPA isolates from four European countries revealed a 14.3% prevalence of azole resistance, all linked to known genetic mutations.
  • The findings suggest that monitoring for resistant strains and potentially updating antifungal treatment guidelines could improve patient outcomes among those suspected of having CAPA.
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Background: Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort.

Methods: From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs).

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Objectives: Pneumocystis pneumonia (PCP) is an opportunistic infection that causes significant morbidity and mortality in the immunocompromised population. This population is growing and diversifying, yet contemporary epidemiology is lacking. We investigated the population-level incidence of PCP over the past decade.

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  • Phosphodiesterase 3A gain-of-function mutations lead to hypertension and stroke, but surprisingly do not cause cardiac hypertrophy or heart failure in affected patients, suggesting a potential protective mechanism in the heart.* -
  • Researchers used CRISPR-Cas9 models and human stem cells to analyze the effects of these mutations, observing that new mutations could enhance enzyme activity and self-assembly while preserving normal heart structure despite high blood pressure.* -
  • In their experiments, cardiac responses in mutant models showed adaptive changes in calcium cycling and similarities in heart function to normal (wild-type) rats, indicating the mutations might lead to beneficial heart adaptations under certain conditions.*
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Background: ICUs are settings of high antifungal consumption. There are few data on prescribing practices in ICUs to guide antifungal stewardship implementation in this setting.

Methods: An antifungal therapy (AFT) service evaluation (15 May-19 November 2019) across ICUs at three London hospitals, evaluating consumption, prescribing rationale, post-prescription review, de-escalation and final invasive fungal infection (IFI) diagnostic classification.

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Pseudomonas aeruginosa is the most common pathogen infecting the lungs of people with cystic fibrosis (CF), causing both acute and chronic infections. Intrinsic and acquired antibiotic resistance, coupled with the physical barriers resulting from desiccated CF sputum, allow P. aeruginosa to colonize and persist in spite of antibiotic treatment.

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  • Infections from the fungal pathogen Aspergillus fumigatus are showing increasing resistance to standard azole antifungal treatments, yet there's limited knowledge on how patients acquire these drug-resistant strains from the environment.
  • A study analyzing 218 fungal isolates from the UK and Ireland revealed two main genetic groups (clades A and B), with most environmental resistance found in clade A and strong evidence of patients getting infections from environmental sources.
  • The research also identified genetic regions under positive selection that relate to azole resistance, highlighting the need for more understanding of how these fungi develop drug resistance, particularly in patients who are already vulnerable due to respiratory infections.
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  • Bronchiectasis is a common complication found in patients with primary antibody deficiency (PAD) syndromes, particularly common variable immune deficiency (CVID).
  • A study analyzed patients with CVID and specific antibody deficiency, revealing that the severity of bronchiectasis at diagnosis correlates with higher mortality rates.
  • Factors such as lower FEV (Forced Expiratory Volume), lung colonization, and a COPD diagnosis were also linked to increased mortality in these patients.
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Background is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.

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Background: The sudden increase in COVID-19 admissions in hospitals during the SARS-CoV-2 pandemic of 2020 led to onward transmissions among vulnerable inpatients.

Aims: This study was performed to evaluate the prevalence and clinical outcomes of healthcare-associated COVID-19 infections (HA-COVID-19) during the 2020 epidemic and study factors which may promote or correlate with its incidence and transmission in a Teaching Hospital NHS Trust in London, UK.

Methods: Electronic laboratory, patient and staff self-reported sickness records were interrogated from 1 March to 18 April 2020.

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Objectives: Antimicrobial resistance is a major threat to public health. New drugs such as Ceftazidime/avibactam have been developed for the treatment of Multi-Drug resistant (MDR) pathogens. Susceptibility can be variable and inappropriate use can add a financial strain on the National Health Service (NHS).

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