Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading DOI Creative Commons
Johannes Boyer, Simon Feys,

Isabella Zsifkovits

et al.

Mycopathologia, Journal Year: 2023, Volume and Issue: 188(5), P. 667 - 681

Published: April 26, 2023

Abstract Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients hence vulnerable hosts increases, which is paralleled by emergence rise IA cases. Increased frequencies azole-resistant strains are reported from six continents, presenting new challenge for therapeutic management. Treatment options currently consist three classes antifungals (azoles, polyenes, echinocandins) with distinctive advantages shortcomings. Especially settings difficult to treat IA, comprising drug tolerance/resistance, limiting drug–drug interactions, and/or severe underlying organ dysfunction, novel approaches urgently needed. Promising drugs late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix Gwt1 enzyme ibrexafungerp triterpenoid), opelconazole (an azole optimized inhalation) rezafungin echinocandin long half-life time). Further, insights pathophysiology yielding immunotherapy as potential add-on therapy. Current investigations show encouraging results, so far mostly preclinical settings. In this review we discuss current strategies, give an outlook on possible pharmaceutical options, and, lastly, provide overview ongoing research IA.

Language: Английский

Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management DOI
George R. Thompson, Jeffrey D. Jenks, John W. Baddley

et al.

Clinical Microbiology Reviews, Journal Year: 2023, Volume and Issue: 36(3)

Published: July 13, 2023

Fungal endocarditis accounts for 1% to 3% of all infective cases, is associated with high morbidity and mortality (>70%), presents numerous challenges during clinical care. Candida spp. are the most common causes fungal endocarditis, implicated in over 50% followed by Aspergillus Histoplasma Important risk factors include prosthetic valves, prior heart surgery, injection drug use.

Language: Английский

Citations

43
The changing epidemiology of fungal infections DOI Creative Commons
Cornelia Lass‐Flörl, Stephan Steixner

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 94, P. 101215 - 101215

Published: Oct. 5, 2023

Invasive fungal diseases are common complications in critically ill patients and those with significant underlying imbalanced immune systems. Fungal co-, and/or super-infections emerging have become a rising concern within the last few years. In Europe, cases of candidiasis aspergillosis dominate, followed by mucormycosis India. Epidemiological studies show an increasing trend incidence all three entities. Parallel to this, shift pathogens is observed. More non-albicans Candida infections cryptic species on rise; may cover intrinsic resistance azoles other antifungal drugs. The recent COVID-19 pandemic led significantly invasive among hospitalized patients.

Language: Английский

Citations

43
Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease DOI
Martin Hoenigl, Amir Arastehfar, Maiken Cavling Arendrup

et al.

Clinical Microbiology Reviews, Journal Year: 2024, Volume and Issue: 37(2)

Published: April 11, 2024

SUMMARYFungal infections are on the rise, driven by a growing population at risk and climate change. Currently available antifungals include only five classes, their utility efficacy in antifungal treatment limited one or more of innate acquired resistance some fungi, poor penetration into "sequestered" sites, agent-specific side effect which require frequent patient reassessment monitoring. Agents with novel mechanisms, favorable pharmacokinetic (PK) profiles including good oral bioavailability, fungicidal mechanism(s) urgently needed. Here, we provide comprehensive review agents, both improved known mechanisms actions new currently clinical development for treating invasive yeast, mold (filamentous fungi),

Language: Английский

Citations

34
Risk factors for COVID-19-associated pulmonary aspergillosis: a systematic review and meta-analysis DOI
Francesca Gioia, Laura N. Walti, Ani Orchanian‐Cheff

et al.

The Lancet Respiratory Medicine, Journal Year: 2024, Volume and Issue: 12(3), P. 207 - 216

Published: Jan. 4, 2024

Language: Английский

Citations

25
New treatment options for critically important WHO fungal priority pathogens DOI Creative Commons
Lisa Kriegl, Matthias Egger, Johannes Boyer

et al.

Clinical Microbiology and Infection, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

BackgroundYet often overlooked in public health discourse, fungal infections pose a crucialglobal disease burden associated with annual mortality rates approximately equal to tuberculosis and HIV. In response, the World Health Organization (WHO) published its first global priority list of pathogens 2022 assigning Aspergillus fumigatus, Candida albicans, auris, Cryptococcus neoformans critical group.ObjectivesThis review provides succinct insights on novel antifungals development, aiming contribute valuable information perspectives focus recent clinical findings new treatment approaches for members WHO pathogen list.SourcesPubMed literature search using "Aspergillus fumigatus," "Cryptococcus neoformans," "Candida auris," albicans," along names antifungal substances, including "fosmanogepix", "ibrexafungerp", "opelconazole", "oteseconazole", "MAT2203", "olorofim", "rezafungin" was conducted.ContentForeach pathogen, current issues data from trials are covered. The remarkable development three therapeutics recently receiving Food Drug Administration (FDA) approval (ibrexafungerp -June 2021, oteseconazole -April 2022, rezafungin -March 2023) is outlined, two more exciting namely olorofim fosmanogepix expecting within next years. Ibrexafungerp, have additionally been granted orphan drug status by European Medicines Agency (EMA) Europe -November -July -January 2024).ImplicationsWhile limited number targets emergence resistance posed challenges treatment, drugs such as ibrexafungerp, rezafungin, fosmanogepix, or shown promising efficacy. These not only provide alternative options invasive but also alleviate outpatient settings. More data, implementation stewardship programs, surveillance, utilization agriculture necessary prevent ensure safety efficacy these agents.

Language: Английский

Citations

19
Fungal impacts on Earth’s ecosystems DOI
Nicola T. Case, Sarah J. Gurr, Matthew C. Fisher

et al.

Nature, Journal Year: 2025, Volume and Issue: 638(8049), P. 49 - 57

Published: Feb. 5, 2025

Language: Английский

Citations

4
Editorial: The World Health Organization (WHO) Fungal Priority Pathogens List in Response to Emerging Fungal Pathogens During the COVID-19 Pandemic DOI

Dinah V. Parums

Medical Science Monitor, Journal Year: 2022, Volume and Issue: 28

Published: Dec. 1, 2022

The COVID-19 pandemic, climate change, increased resistance to antifungal drugs, and an number of immunocompromised patients have driven a recent global surge in pathogenic fungal infections, including aspergillosis, candidiasis, mucormycosis. On 25 October 2022, the World Health Organization (WHO) released list 19 priority pathogens identified as having greatest threat public health. WHO Fungal Priority Pathogens List represents first response identify prioritize their impact on health consider unmet research development needs. has grouped into those critical, high, medium priority. This Editorial aims highlight importance identifying prioritizing emerging factors driving changing patterns infection.

Language: Английский

Citations

61
Pathogenicity and virulence of Aspergillus fumigatus DOI Creative Commons
Kayleigh Earle, Clara Valero, Daniel P. Conn

et al.

Virulence, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 8, 2023

Pulmonary infections caused by the mould pathogen Aspergillus fumigatus are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral bacterial pulmonary recognised risks factors for development aspergillosis. In this review, we will summarise our current knowledge mechanistic basis aspergillosis with focus on emerging at-risk populations.

Language: Английский

Citations

41
Immunity to fungi in the lung DOI Creative Commons
Lena J. Heung,

Darin L. Wiesner,

Keyi Wang

et al.

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 66, P. 101728 - 101728

Published: Feb. 24, 2023

Language: Английский

Citations

40
Environmental reservoirs of the drug-resistant pathogenic yeast Candida auris DOI Creative Commons
Ayorinde B. Akinbobola, Ryan Kean, Syed Manzoor Ahmed Hanifi

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(4), P. e1011268 - e1011268

Published: April 13, 2023

Candia auris is an emerging human pathogenic yeast; yet, despite phenotypic attributes and genomic evidence suggesting that it probably emerged from a natural reservoir, we know nothing about the environmental phase of its life cycle transmission pathways associated with it. The thermotolerant characteristics C. have been hypothesised to be adaptation increasing temperatures due global warming (which may facilitated ability tolerate mammalian thermal barrier considered protective strategy for humans against colonisation by fungi potential). Thus, first fungus as result climate change. In addition, release antifungal chemicals, such azoles, into environment (from both pharmaceutical agricultural sources) likely responsible enrichment resistant strains auris; however, survival dissemination in poorly understood. this paper, critically review possible through which can introduced evaluate influence persistence environments. Identifying potential niches reservoirs understanding emergence backdrop change pollution will crucial development effective epidemiological management responses.

Language: Английский

Citations

38