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Cureus Apr 2024Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including and , as well as molds. It... (Review)
Review
Fosmanogepix, a prodrug of Manogepix (MGX), is a groundbreaking antifungal agent with broad-spectrum activity against yeasts, including and , as well as molds. It exhibits effectiveness against drug-resistant strains, such as strains resistant to and strains resistant to azoles. Furthermore, fosmanogepix shows activity against pathogens that typically resist other classes of drugs, such as , , and , although its efficacy against Mucorales varies. In animal models, fosmanogepix has demonstrated notable effectiveness against disseminated infections caused by various species, , and . It has also shown efficacy in pulmonary infection models involving , , , , and . Clinical trials have revealed excellent oral bioavailability (>90%), enabling a seamless transition between intravenous and oral formulations without compromising blood concentrations. Fosmanogepix exhibits favorable profiles in terms of drug interactions, tolerability, and extensive distribution in various tissues, making it an appealing choice for treating invasive fungal infections. This comprehensive review aims to examine the outcomes of published data on fosmanogepix, encompassing in vitro, in vivo, and clinical investigations.
PubMed: 38807795
DOI: 10.7759/cureus.59210 -
Emerging Infectious Diseases Jun 2024Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously... (Observational Study)
Observational Study Review
Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease--related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.
Topics: Humans; Scedosporium; France; Male; Middle Aged; Aged; Female; Mycoses; Adult; Antifungal Agents; Aged, 80 and over; Invasive Fungal Infections
PubMed: 38781681
DOI: 10.3201/eid3006.231409 -
Therapeutic Advances in Respiratory... 2024A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still...
BACKGROUND
A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden.
OBJECTIVES
The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden.
DESIGN
The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor.
METHODS
Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed.
RESULTS
Lung function measured as ppFEV1 ( < 0.001), body mass index (BMI) in adults ( < 0.001), and BMI -score in children ( = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of ( = 0.007) and ( < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for ( = 0.009), spp ( = 0.026), and ( < 0.001) shifted from negative to positive.
CONCLUSION
The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for , or , key pathogens in the CF context.
Topics: Humans; Cystic Fibrosis; Male; Prospective Studies; Female; Aminophenols; Benzodioxoles; Child; Adult; Young Adult; Adolescent; Drug Combinations; Aminopyridines; Quinolones; Sweden; Treatment Outcome; Mycoses; Respiratory Tract Infections; Cystic Fibrosis Transmembrane Conductance Regulator; Lung; Chloride Channel Agonists; Time Factors; Fungi; Bacterial Infections
PubMed: 38780228
DOI: 10.1177/17534666241254090 -
Journal of Hazardous Materials May 2024Spent mushroom substrate (SMS) holds valuable microbiota that can be useful in remediating polluted soils with hydrocarbons. However, the microorganisms behind the...
Spent mushroom substrate (SMS) holds valuable microbiota that can be useful in remediating polluted soils with hydrocarbons. However, the microorganisms behind the bioremediation process remain uncertain. In this work, a bioremediation assay of total petroleum hydrocarbons (TPHs) polluted soil by SMS application was performed to elucidate the microorganisms and consortia involved in biodegradation by a metabarcoding analysis. Untreated polluted soil was compared to seven bioremediation treatments by adding SMS of Agaricus bisporus, Pleurotus eryngii, Pleurotus ostreatus, and combinations. Soil microbial activity, TPH biodegradation, taxonomic classification, and predictive functional analysis were evaluated in the microbiopiles at 60 days. Different metagenomics approaches were performed to understand the impact of each SMS on native soil microbiota and TPHs biodegradation. All SMSs enhanced the degradation of aliphatic and aromatic hydrocarbons, being A. bisporus the most effective, promoting an efficient consortium constituted by the bacterial families Alcanivoraceae, Alcaligenaceae, and Dietziaceae along with the fungal genera Scedosporium and Aspergillus. The predictive 16 S rRNA gene study partially explained the decontamination efficacy by observing changes in the taxonomic structure of bacteria and fungi, and changes in the potential profiles of estimated degradative genes across the different treatments. This work provides new insights into TPHs bioremediation.
PubMed: 38776816
DOI: 10.1016/j.jhazmat.2024.134650 -
Allergologie Select 2024None.
None.
PubMed: 38756207
DOI: 10.5414/ALX02444E -
Mikrobiyoloji Bulteni Apr 2024Scedosporium/Lomentospora is an opportunistic fungal pathogen found worldwide. While Scedosporium apiospermum and Scedosporium boydii are commonly observed globally,...
Scedosporium/Lomentospora is an opportunistic fungal pathogen found worldwide. While Scedosporium apiospermum and Scedosporium boydii are commonly observed globally, Lomentospora prolificans, which mainly affects immunosuppressed individuals, is rarely encountered and is more prevalent in arid climates, particularly in Australia and Spain. L.prolificans is a fungus commonly found in environmental sources such as contaminated water and soil. This species is known as an opportunistic pathogen that can cause deep-seated fungal infections, especially in immunosuppressed individuals. In this case report, a fatal case of L.prolificans fungemia in a patient with T-cell large granular leukemia during profound neutropenia was presented. The patient admitted to the hospital with prolonged fever, neutropenia, and shortness of breath. Antibiotherapy was administered to the patient for febrile neutropenia, but the fever persisted and his clinical status rapidly deteriorated. L.prolificans was isolated from the blood culture, and considering its antifungal resistance, combination therapy of voriconazole and terbinafine was initiated. However, the patient died of septic shock and multiple organ failure. In conclusion, although L.prolificans infections are rare, they can be life-threatening, especially in immunosuppressed individuals. Diagnosis and treatment of such infections may be difficult, therefore rapid diagnostic methods and appropriate treatment protocols should be developed. Consideration of infections caused by rare fungal pathogens in patients with risk factors may be critical for patient care. The literature review revealed that the first case of L.prolificans fungemia from Türkiye was reported in 2023. This case presentation represents the second reported case. However, in our case, L.prolificans fungemia occurred in 2018, it can be considered that L.prolificans may have been an invasive fungal pathogen of significant concern in Türkiye much earlier than previously documented.
Topics: Humans; Fatal Outcome; Fungemia; Antifungal Agents; Male; Voriconazole; Terbinafine; Shock, Septic; Immunocompromised Host; Opportunistic Infections; Drug Therapy, Combination; Middle Aged; Scedosporium
PubMed: 38676587
DOI: 10.5578/mb.202498145 -
Journal of Fungi (Basel, Switzerland) Apr 2024Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem...
Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by spp. (respectively 14.5% and 26.1%) and spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for spp., spp. or multiple pathogens IMD compared with or other pathogens (51.7% vs. 17.6%, < 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84, = 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.
PubMed: 38667960
DOI: 10.3390/jof10040289 -
Journal of Fungi (Basel, Switzerland) Apr 2024The Mediterranean Sea stands out as a hotspot of biodiversity, whose fungal composition remains underexplored. Marine sediments represent the most diverse substrate;...
The Mediterranean Sea stands out as a hotspot of biodiversity, whose fungal composition remains underexplored. Marine sediments represent the most diverse substrate; however, the challenge of recovering fungi in culture hinders the precise identification of this diversity. Concentration techniques like skimmed milk flocculation (SMF) could represent a suitable solution. Here, we compare the effectiveness in recovering filamentous ascomycetes of direct plating and SMF in combination with three culture media and two incubation temperatures, and we describe the fungal diversity detected in marine sediments. Sediments were collected at different depths on two beaches (Miracle and Arrabassada) on the Spanish western Mediterranean coast between 2021 and 2022. We recovered 362 strains, and after a morphological selection, 188 were identified primarily with the LSU and ITS barcodes, representing 54 genera and 94 species. , , and were the most common genera, with different percentages of abundance between both beaches. Arrabassada Beach was more heterogeneous, with 42 genera representing 60 species (Miracle Beach, 28 genera and 54 species). Although most species were recovered with direct plating (70 species), 20 species were exclusively obtained using SMF as a sample pre-treatment, improving our ability to detect fungi in culture. In addition, we propose three new species in the genera , , and , and a fourth representing the novel genus . We concluded that SMF is a useful technique that, in combination with direct plating, including different culture media and incubation temperatures, improves the chance of recovering marine fungal communities in culture-dependent studies.
PubMed: 38667952
DOI: 10.3390/jof10040281 -
Journal of Fungi (Basel, Switzerland) Apr 2024The release of extracellular vesicles (EVs) has been implicated as an alternative transport mechanism for the passage of macromolecules through the fungal cell wall, a...
The release of extracellular vesicles (EVs) has been implicated as an alternative transport mechanism for the passage of macromolecules through the fungal cell wall, a phenomenon widely reported in yeasts but poorly explored in mycelial cells. In the present work, we have purified and characterized the EVs released by mycelia of the emerging, opportunistic, widespread and multidrug-resistant filamentous fungus . Transmission electron microscopy images and light scattering measurements revealed the fungal EVs, which were observed individually or grouped with heterogeneous morphology, size and electron density. The mean diameter of the EVs, evaluated by the light scattering technique, was 179.7 nm. Overall, the structural stability of EVs was preserved during incubation under various storage conditions. The lipid, carbohydrate and protein contents were quantified, and the EVs' protein profile was evidenced by SDS-PAGE, revealing proteins with molecular masses ranging from 20 to 118 kDa. Through immunoblotting, ELISA and immunocytochemistry assays, antigenic molecules were evidenced in EVs using a polyclonal serum (called anti-secreted molecules) from a rabbit inoculated with conditioned cell-free supernatant obtained from mycelial cells. By Western blotting, several antigenic proteins were identified. The ELISA assay confirmed that the anti-secreted molecules exhibited a positive reaction up to a serum dilution of 1:3200. Despite transporting immunogenic molecules, EVs slightly induced an in vitro cytotoxicity effect after 48 h of contact with either macrophages or lung epithelial cells. Interestingly, the pretreatment of both mammalian cells with purified EVs significantly increased the association index with conidia. Furthermore, EVs were highly toxic to , leading to larval death in a typically dose- and time-dependent manner. Collectively, the results represent the first report of detecting EVs in the filamentous form, highlighting a possible implication in fungal pathogenesis.
PubMed: 38667948
DOI: 10.3390/jof10040277 -
Diagnostics (Basel, Switzerland) Apr 2024species are human pathogenic fungi, responsible for chronic, localised, and life-threatening disseminated infections in both immunocompetent and immunocompromised...
species are human pathogenic fungi, responsible for chronic, localised, and life-threatening disseminated infections in both immunocompetent and immunocompromised individuals. The diagnosis of infections currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and the time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect -specific biomarkers. Here, we report the development of a rapid (30 min) and sensitive (pmol/L sensitivity) lateral-flow device (LFD) test, incorporating a -specific IgG1 monoclonal antibody (mAb), HG12, which binds to extracellular polysaccharide (EPS) antigens between ~15 kDa and 250 kDa secreted during the hyphal growth of the pathogens. The test is compatible with human serum and allows for the detection of the species most frequently reported as agents of human disease (, , and ), with limits of detection (LODs) of the EPS biomarkers in human serum of ~0.81 ng/mL (), ~0.94 ng/mL (), and ~1.95 ng/mL (). The -specific LFD (LFD) test therefore provides a potential novel opportunity for the detection of infections caused by different species.
PubMed: 38667492
DOI: 10.3390/diagnostics14080847