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Future Microbiology Nov 2023Fungal infections are a serious problem affecting many people worldwide, creating critical economic and medical consequences. Fungi are ubiquitous and can cause invasive... (Review)
Review
Fungal infections are a serious problem affecting many people worldwide, creating critical economic and medical consequences. Fungi are ubiquitous and can cause invasive diseases in individuals mostly living in developing countries or with weakened immune systems, and antifungal drugs currently available have important limitations in tolerability and efficacy. In an effort to counteract the high morbidity and mortality rates associated with invasive fungal infections, various approaches are being utilized to discover and develop new antifungal agents. This review discusses the challenges posed by fungal infections, outlines different methods for developing antifungal drugs and reports on the status of drugs currently in clinical trials, which offer hope for combating this serious global problem.
Topics: Humans; Antifungal Agents; Mycoses; Invasive Fungal Infections; Fungi
PubMed: 37750748
DOI: 10.2217/fmb-2022-0269 -
Frontiers in Cellular and Infection... 2024Mucormycosis is still regarded a rare fungal infection, but the high incidences of COVID-associated cases in India and other countries have shown its potential threat to... (Review)
Review
Mucormycosis is still regarded a rare fungal infection, but the high incidences of COVID-associated cases in India and other countries have shown its potential threat to large patient cohorts. In addition, infections by these fast-growing fungi are often fatal and cause disfigurement, badly affecting patients' lives. In advancing our understanding of pathogenicity factors involved in this disease, to enhance the diagnostic toolset and to evaluate novel treatment regimes, animal models are indispensable. As ethical and practical considerations typically favor the use of alternative model systems, this review provides an overview of alternative animal models employed for mucormycosis and discusses advantages and limitations of the respective model.
Topics: Animals; Humans; Mucormycosis; Mycoses; Fungi; Disease Models, Animal; India
PubMed: 38362495
DOI: 10.3389/fcimb.2024.1343834 -
The Lancet. Child & Adolescent Health Jun 2024
Topics: Child; Humans; Mycoses
PubMed: 38648807
DOI: 10.1016/S2352-4642(24)00056-7 -
Intensive Care Medicine Apr 2024The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host...
PURPOSE
The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs).
METHODS
After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method.
RESULTS
Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.
Topics: Adult; Humans; Consensus; Invasive Fungal Infections; Aspergillosis; Candidiasis, Invasive; Intensive Care Units
PubMed: 38512399
DOI: 10.1007/s00134-024-07341-7 -
Seminars in Respiratory and Critical... Feb 2024As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge... (Review)
Review
As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge of the diagnostic possibilities and especially their limitations is extremely important. In this review, we aim to reflect critically on the available microbiological diagnostic modalities for diagnosis of pulmonary aspergillosis and formulate some future prospects. Timely start of adequate antifungal treatment leads to a better patient outcome, but overuse of antifungals should be avoided. Current diagnostic possibilities are expanding, and are mainly driven by enzyme immunoassays and lateral flow device tests for the detection of antigens. Most of these tests are directed towards similar antigens, but new antibodies towards different targets are under development. For chronic forms of pulmonary aspergillosis, anti- IgG antibodies and precipitins remain the cornerstone. More studies on the possibilities and limitations of molecular testing including targeting resistance markers are ongoing. Also, metagenomic next-generation sequencing is expanding our future possibilities. It remains important to combine different test results and interpret them in the appropriate clinical context to improve performance. Test performances may differ according to the patient population and test results may be influenced by timing, the tested matrix, and prophylactic and empiric antifungal therapy. Despite the increasing armamentarium, a simple blood or urine test for the diagnosis of aspergillosis in all patient populations at-risk is still lacking. Research on diagnostic tools is broadening from a pathogen focus on biomarkers related to the patient and its immune system.
Topics: Humans; Antifungal Agents; Aspergillus; Aspergillosis; Pulmonary Aspergillosis; Lung; Pneumonia; Antibodies
PubMed: 38228164
DOI: 10.1055/s-0043-1776777 -
Clinical Microbiology Reviews Mar 2024Over recent decades, the global burden of fungal disease has expanded dramatically. It is estimated that fungal disease kills approximately 1.5 million individuals... (Review)
Review
Over recent decades, the global burden of fungal disease has expanded dramatically. It is estimated that fungal disease kills approximately 1.5 million individuals annually; however, the true worldwide burden of fungal infection is thought to be higher due to existing gaps in diagnostics and clinical understanding of mycotic disease. The development of resistance to antifungals across diverse pathogenic fungal genera is an increasingly common and devastating phenomenon due to the dearth of available antifungal classes. These factors necessitate a coordinated response by researchers, clinicians, public health agencies, and the pharmaceutical industry to develop new antifungal strategies, as the burden of fungal disease continues to grow. This review provides a comprehensive overview of the new antifungal therapeutics currently in clinical trials, highlighting their spectra of activity and progress toward clinical implementation. We also profile up-and-coming intracellular proteins and pathways primed for the development of novel antifungals targeting their activity. Ultimately, we aim to emphasize the importance of increased investment into antifungal therapeutics in the current continually evolving landscape of infectious disease.
Topics: Humans; Antifungal Agents; Mycoses; Drug Resistance, Fungal
PubMed: 38294218
DOI: 10.1128/cmr.00142-23 -
Chest Nov 2023Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality.
BACKGROUND
Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality.
RESEARCH QUESTION
Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient's underlying condition?
STUDY DESIGN AND METHODS
All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally.
RESULTS
A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
INTERPRETATION
Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL.
Topics: Humans; Mucormycosis; Retrospective Studies; Lung Diseases, Fungal; Neutropenia
PubMed: 37419276
DOI: 10.1016/j.chest.2023.06.039 -
JAMA Apr 2024
Topics: Humans; Climate Change; Communicable Diseases; Climatic Processes; Extreme Weather; Wildfires; Greenhouse Gases; Fossil Fuels; Disease Vectors; Zoonoses; Mycoses; Waterborne Diseases; Education, Medical; Public Policy
PubMed: 38506835
DOI: 10.1001/jama.2023.27724 -
Nature Reviews. Cancer May 2024
Topics: Humans; Neoplasms; Fungi; Animals; Mycoses
PubMed: 38347100
DOI: 10.1038/s41568-024-00665-y -
RMD Open Aug 2023We aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality.
OBJECTIVES
We aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality.
METHODS
We analysed cases of IFD associated with AID from the surveillance network of invasive fungal diseases (Réseau de surveillance des infections fongiques invasives, RESSIF) registry of the French national reference centre for invasive mycoses. We studied association of AID-specific treatments with 30-day mortality. We analysed total lymphocyte and CD4-T cell counts in patients with pneumonia (PCP).
RESULTS
From 2012 to 2018, 549 individuals with IFD and AID were included, mainly with PCP (n=227, 41.3%), fungemia (n=167, 30.4%) and invasive aspergillosis (n=84, 15.5%). Rheumatoid arthritis (RA) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) were the most frequent AID in PCP (n=55 and 25, respectively) and invasive aspergillosis (n=15 and 10, respectively), inflammatory bowel diseases (IBDs) were predominant in fungemia (n=36). At IFD diagnosis, 365 (66.5%) patients received glucocorticoids (GCs), 285 (51.9%) immunosuppressants, 42 (7.7%) tumor necrosis factor (TNF)-α blockers, 75 (13.7%) other biologics. Mortality at 30 days was 28.1% (143/508). Fungemia and high-dose GCs were independently associated with higher 30-day mortality. In PCP patients, lymphopenia <1500/mm was frequent (132/179, 73.7%) even if CD4+T cell count exceeded 200/mm in 56/78 patients (71.8%) (median 472.5/mm, IQR 160-858).
CONCLUSION
IFD associated with AID occurs primarily in RA, AAV and IBD, especially when treated with GCs and immunosuppressants. Mortality is high, especially for patients on high-dose GCs. Lymphopenia may help identify risk of PCP, but normal CD4+T cell count does not rule out the risk. Further studies are needed to assess the individual risk factors for IFD.
Topics: Autoimmune Diseases; Invasive Fungal Infections; Humans; Male; Female; Middle Aged; Aged; Glucocorticoids; Immunosuppressive Agents; Risk Factors; France; Prevalence
PubMed: 37558492
DOI: 10.1136/rmdopen-2023-003281