Aspergillus and Host-Pathogen Interaction: Focus on treatment-relevant aspects.

Background: Invasive aspergillosis (IA) remains a major cause of morbidity and mortality in immunocompromised individuals, with an expanding spectrum of at-risk populations, particularly in the intensive care settings. Despite advances in antifungal pharmacotherapy, treatment outcomes remain suboptimal, and the rise of antifungal resistance highlights the need for adjunctive therapy that leverage host immune mechanisms. The pathogenesis of IA is primarily driven by impaired or dysregulated immune responses to Aspergillus species, mainly Aspergillus fumigatus.

Association between allergic bronchopulmonary aspergillosis or Aspergillus sensitization and tuberculosis: A systematic review of 607 cases.

Introduction: Although allergic bronchopulmonary aspergillosis (ABPA) is classically described in asthma and cystic fibrosis, pulmonary tuberculosis (PTB) with post-tubercular lung disease (PTLD) has been reported as a likely predisposing factor. It, however, has not been reviewed systematically, which we aimed to achieve in the current systematic review.

Methods: We screened the available literature from PubMed, Embase, SCOPUS and Web of Science databases for studies reporting association between ABPA and PTB from the beginning of time to June 30, 2023 and collated the data on association of ABPA and tuberculosis.

Olorofim for the treatment of invasive fungal diseases in patients with few or no therapeutic options: a single-arm, open-label, phase 2b study.

Background: Only a small number of antifungal therapies for invasive fungal disease (IFD) are currently available, and many pathogens are resistant to one or more of these therapies. Olorofim, the first orotomide antifungal agent to be developed, is active against fungi that are resistant to registered therapies. It impairs fungal pyrimidine biosynthesis, leading to cell death.

A Global Analysis of Cases of Mucormycosis Recorded in the European Confederation of Medical Mycology / International Society for Human and Animal Mycology (ECMM / ISHAM) Zygomyco.net Registry from 2009 to 2022.

We analyzed mucormycosis data from the Zygomyco.net registry (2009-2022), encompassing cases from 16 countries. India, Russia and the Czech Republic provided the largest contributions.

Climate change: shifting boundaries of fungal disease in Europe and beyond.

Climate change is altering ecosystems worldwide. While shifting environmental conditions are complex, it has been hypothesised that the impact of climate change is directly leading to increases in fungal infections across the globe. Rising temperatures, changing precipitation patterns and extreme weather events are thought to be driving the adaptation of fungal pathogens to new climates, expanding their geographical range and posing a growing threat to human health and agriculture.

Diagnosis and treatment of invasive pulmonary aspergillosis in critically ill intensive care patients: executive summary of the German national guideline (AWMF 113-005).

Purpose: The executive summary of the guideline aims to provide the most relevant recommendations on the diagnosis and treatment of invasive pulmonary aspergillosis in critically ill patients in the intensive care unit.

Methods: The guideline's work included a systematic literature search, selection and assessment of the data relevant to the issues identified. Key questions included the areas of epidemiology, risk factors, diagnostics, and therapy.

Diagnosis and management of Candida endophthalmitis and chorioretinitis.

Background: Candida endophthalmitis (CE) and chorioretinitis are uncommon but potentially devastating complications of candidemia, associated with significant risks of vision loss and long-term morbidity. Effective management relies on timely diagnosis and targeted antifungal therapy. However, diagnostic and therapeutic approaches are hindered by inconsistent guidelines, limited evidence, and variations in clinical practice.

Antifungal pipeline: New tools for the treatment of mycoses.

Fungal infections are becoming an escalating public health challenge, particularly among immunocompromised individuals. The partially limited efficacy of current antifungal treatments, their potential adverse effects, and the increasing problem of resistance emphasize the need for new treatment options. Existing antifungal classes-allylamines, azoles, echinocandins, polyenes, and pyrimidine analogs-face challenges due to their similarity with human cells and rising resistance.

Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in cooperation with ISHAM and ASM.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals.

Rezafungin in special populations with candidaemia and/or invasive candidiasis.

Achieving and maintaining therapeutic drug exposures with antifungals can be challenging in special patient populations, such as those with organ dysfunction (liver or kidney) or obesity, or elderly patients, due to dose-exposure relationships and potential drug-drug interactions. Dose adjustments may be needed in these populations to maintain therapeutic efficacy and/or prevent toxicity. We reviewed specific dosing considerations for antifungals in special populations with candidaemia and/or invasive candidiasis, focusing on those relating to echinocandins (based on prescribing information), and then explored the utility of the second-generation echinocandin rezafungin in treating these populations (based on currently available data identified from a PubMed and congress abstract search).

Pulmonary Coinfection of and Species.

In this multicenter study of 387 patients who were immunocompromised, 4.5% with invasive pulmonary aspergillosis also had pneumonia. Predictors of coinfection included elevated β-D-glucan and prolonged corticosteroid use.

Posaconazole for Prevention of COVID-19-Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients: A European Multicentre Case-Control Study (POSACOVID).

Background: This study investigated the impact of posaconazole (POSA) prophylaxis in COVID-19 patients with acute respiratory failure receiving systemic corticosteroids on the risk for the development of COVID-19-associated pulmonary aspergillosis (CAPA).

Methods: The primary aim of this prospective, multicentre, case-control study was to assess whether application of POSA prophylaxis in mechanically ventilated COVID-19 patients reduces the risk for CAPA development. All consecutive patients from centre 1 (cases) who received POSA prophylaxis as standard-of-care were matched to one subject from centre 2 and centre 3 who did not receive any antifungal prophylaxis, using propensity score matching for the following variables: (i) age, (ii) sex, (iii) treatment with tocilizumab and (iv) time at risk.

Advancing Patient Advocacy in Mycology: Cultivating Collaboration in Education, Research, and Policy.

In the healthcare landscape, diseases such as cancer and HIV/AIDS have benefited from the patient's perspective. For fungal diseases, the patient voice remains absent in critical areas such as policy formulation, funding decisions, and research priorities. Patients affected by fungal disease, along with their caregivers and advocacy groups, possess invaluable insights into the challenges and unmet needs they face.

Comparative efficacy and safety of treatment regimens for Pneumocystis jirovecii pneumonia in people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.

Background: Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in people living with HIV (PWH) who have low CD4 counts. Despite its side effects, trimethoprim-sulfamethoxazole (TMP-SMX) is currently considered the primary treatment for PCP.

Objectives: The objectives of this study are to compare the efficacy (treatment failure and mortality) and tolerability (treatment change) of PCP treatment regimens with a frequentist network meta-analysis.

Climate Change and Medical Mycology.

This review explores how climate change influences fungal disease dynamics, focusing on emergence of new fungal pathogens, increased antifungal resistance, expanding geographic ranges of fungal pathogens, and heightened host susceptibility. Rising temperatures and altered precipitation patterns enhance fungal growth and resistance mechanisms, complicating treatment efforts. Climate-driven geographic shifts are expanding the range of diseases like Valley fever, histoplasmosis, and blastomycosis.

Mycobiome analyses of critically ill COVID-19 patients.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID-19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity and colonization. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality.

Nomenclature for human and animal fungal pathogens and diseases: a proposal for standardized terminology.

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status.

Serum antigen tests for the diagnosis of invasive aspergillosis: a retrospective comparison of five antigen assays and one beta-D-glucan assay.

Invasive aspergillosis (IA) is a life-threatening infection. Early and specific diagnosis is pivotal to ensure adequate therapy. Antigen testing from blood is a widespread and convenient diagnostic approach.

Diagnosing fungal infections in clinical practice: a narrative review.

Background: Invasive fungal infections (IFI) present a major medical challenge, with an estimated 6.5 million cases annually, resulting in 3.8 million deaths.

Insights from Three Pan-European Multicentre Studies on Invasive Candida Infections and Outlook to ECMM Candida IV.

Invasive candidiasis and candidemia remain a significant public health concern. The European Confederation of Medical Mycology (ECMM) conducted three pan-European multicentre studies from 1997 to 2022 to investigate various aspects of invasive Candida infections. These studies revealed shifting trends in Candida species distribution, with an increase of non-albicans Candida species as causative pathogens, increasing rates of antifungal resistance, and persistently high mortality rates.