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Revista Iberoamericana de Micologia 2021
Topics: Antifungal Agents; Fungi; Scedosporium
PubMed: 34247934
DOI: 10.1016/j.riam.2021.05.001 -
Journal of Pharmacy Practice Feb 2022Posaconazole is widely used in lung transplant recipients as pre-emptive therapy or universal fungal prophylaxis. In this patient group, posaconazole is increasingly...
Posaconazole is widely used in lung transplant recipients as pre-emptive therapy or universal fungal prophylaxis. In this patient group, posaconazole is increasingly used instead of voriconazole due to the concerns of an increased risk of squamous cell carcinoma (SCC) with voriconazole, particularly with its long-term use. Dose dependent toxicity has not been identified for posaconazole in the registration trials of intravenous (IV) and modified-release tablet formulations. This is supported by post-marketing experience. We describe a lung transplant recipient who experienced dementia-like symptoms almost 3 years after commencing posaconazole for treatment of complex and (formerly ) fungal infections. Symptoms resolved upon discontinuation of posaconazole, but recurred when re-challenged at a lower dose more than a year later. To the best of our knowledge, this is the first case reporting a dementia-like state with posaconazole.
Topics: Antifungal Agents; Dementia; Humans; Triazoles; Voriconazole
PubMed: 33084474
DOI: 10.1177/0897190020958235 -
Virulence Dec 2021The slowing-down drug-discovery emphasized the importance of repurposing old drugs. This is particularly true when combating infections caused by therapy-refractory...
The slowing-down drug-discovery emphasized the importance of repurposing old drugs. This is particularly true when combating infections caused by therapy-refractory microorganisms, such as species and . Recent studies on responses to oxidative stress underscored the importance of targeting the underlying mechanisms. Auranofin, ebselen, PX-12, honokiol, and to a lesser extent, conoidin A are known to disturb redox-homeostasis systems in many organisms. Their antifungal activity was assessed against 27 isolates belonging to the major species: , and . Auranofin and honokiol were the most active against all species (mean MIC values of 2.875 and 6.143 μg/ml, respectively) and against isolates (mean MIC values of 4.0 and 3.563μg/ml respectively). Combinations of auranofin with voriconazole or honokiol revealed additive effects against 9/27 and 18/27 isolates, respectively. Synergistic interaction between auranofin and honokiol was only found against one isolate of . The effects of auranofin upon exposure to oxidative stress were also investigated. For all species except , the maximal growth in the presence of auranofin significantly decreased when adding a sublethal dose of menadione. The analysis of the expression of genes encoding oxidoreductase enzymes upon exposure of to honokiol unveiled the upregulation of many genes, especially those coding peroxiredoxins, thioredoxin reductases, and glutaredoxins. Altogether, these data suggest that auranofin and honokiol act via dampening the redox balance and support their repurposing as antifungals against species and .
Topics: Antifungal Agents; Auranofin; Biphenyl Compounds; Drug Repositioning; Lignans; Scedosporium
PubMed: 33825667
DOI: 10.1080/21505594.2021.1909266 -
Journal of Fungi (Basel, Switzerland) Jul 2020The incidence of invasive fungal infections caused by molds and endemic fungi is increasing. There is also concern regarding increased rates of reduced susceptibility or... (Review)
Review
The incidence of invasive fungal infections caused by molds and endemic fungi is increasing. There is also concern regarding increased rates of reduced susceptibility or frank resistance among and species, while species, and species are inherently less susceptible or intrinsically resistant to clinically available antifungals. Olorofim (formerly F901318) is the first member of the orotomide class of antifungals to be evaluated clinically for the treatment of invasive mold infections. This agent inhibits dihydroorotate dehydrogenase, a key enzyme in the biosynthesis of pyrimidines. Olorofim has activity against many molds and thermally dimorphic fungi, including species that are resistant to azoles and amphotericin B, but lacks activity against yeasts and the Mucorales. It is currently being developed for both oral and intravenous administration. Although published clinical outcome data have been limited to case reports to date, the results against invasive and refractory infections are promising. This review describes the mechanism of action of olorofim, its in vitro spectrum of activity, and what is currently known about its pharmacokinetic profile and clinical efficacy.
PubMed: 32751765
DOI: 10.3390/jof6030122 -
International Journal of Infectious... Mar 2020Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups,...
OBJECTIVES
Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections.
METHODS
Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected.
RESULTS
Fifty-five children (median age 9 years [IQR: 5-14]) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment. Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days [IQR: 3-28] versus 61 days [IQR: 16-148]). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 [95% CI 1.35-51.40] and HR 6.12 [95% CI 1.52-24.66], respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 [95% CI 0.11-0.99] and HR 0.09 [95% CI 0.02-0.40], respectively).
CONCLUSIONS
Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome.
Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Mycoses; Risk Factors; Scedosporium; Voriconazole
PubMed: 31863876
DOI: 10.1016/j.ijid.2019.12.017 -
Medical Mycology Jun 2024Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In...
Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of infections caused by Fusarium spp., Scedosporium spp., and Lomentospora prolificans to inform the first FPPL. PubMed and Web of Sciences databases were searched to identify studies published between January 1, 2011 and February 23, 2021, reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 20, 11, and 9 articles were included for Fusarium spp., Scedosporium spp., and L. prolificans, respectively. Mortality rates were high in those with invasive fusariosis, scedosporiosis, and lomentosporiosis (42.9%-66.7%, 42.4%-46.9%, and 50.0%-71.4%, respectively). Antifungal susceptibility data, based on small isolate numbers, showed high minimum inhibitory concentrations (MIC)/minimum effective concentrations for most currently available antifungal agents. The median/mode MIC for itraconazole and isavuconazole were ≥16 mg/l for all three pathogens. Based on limited data, these fungi are emerging. Invasive fusariosis increased from 0.08 cases/100 000 admissions to 0.22 cases/100 000 admissions over the time periods of 2000-2009 and 2010-2015, respectively, and in lung transplant recipients, Scedosporium spp. and L. prolificans were only detected from 2014 onwards. Global surveillance to better delineate antifungal susceptibility, risk factors, sequelae, and outcomes is required.
Topics: Humans; Antifungal Agents; Fusarium; Scedosporium; Microbial Sensitivity Tests; World Health Organization; Mycoses; Fusariosis; Ascomycota; Invasive Fungal Infections
PubMed: 38935914
DOI: 10.1093/mmy/myad128 -
Frontiers in Cellular and Infection... 2021and species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising...
and species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the antifungal activity of miltefosine against and species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different and species at 2-4 µg/ml and reduced biofilm formation. The loss of membrane integrity in caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and and cells, highlighting its potential use as new antifungal drug in the future.
Topics: Antifungal Agents; Ascomycota; Humans; Microbial Sensitivity Tests; Phosphorylcholine; Scedosporium
PubMed: 34368017
DOI: 10.3389/fcimb.2021.698662 -
Mycopathologia Dec 2020Scedosporium species are filamentous fungi usually found in sewage and soil from human-impacted areas. They cause a wide range of diseases in humans, from superficial... (Review)
Review
Scedosporium species are filamentous fungi usually found in sewage and soil from human-impacted areas. They cause a wide range of diseases in humans, from superficial infections, such as mycetoma, to invasive and disseminated cases, especially associated in immunocompromised patients. Scedosporium species are also related to lung colonization in individuals presenting cystic fibrosis and are considered one of the most frequent fungal pathogens associated to this pathology. Scedosporium cell wall contains glycosylated molecules involved in important biological events related to virulence and pathogenicity and represents a significant source of antigens. Polysaccharides, peptidopolysaccharides, O-linked oligosaccharides and glycosphingolipids have been identified on the Scedosporium surface. Their primary structures were determined based on a combination of techniques including gas chromatography, ESI-MS, and H and C nuclear magnetic resonance. Peptidorhamnnomannans are common cell wall components among Scedosporium species. Comparing different species, minor structural differences in the carbohydrate portions were detected which could be useful to understand variations in virulence observed among the species. N- and O-linked peptidorhamnomannans are major pathogen-associated molecular patterns and, along with α-glucans, play important roles in triggering host innate immunity. Glycosphingolipids, such as glucosylceramides, have highly conserved structures in Scedosporium species and are crucial for fungal growth and virulence. The present review presents current knowledge on structural and functional aspects of Scedosporium glycoconjugates that are relevant for understanding pathogenicity mechanisms and could contribute to the design of new agents capable of inhibiting growth and differentiation of Scedosporium species. Other cell components such as melanin and ectophosphatases will be also included.
Topics: Cell Wall; Cystic Fibrosis; Glycosphingolipids; Host-Pathogen Interactions; Humans; Mycetoma; Oligosaccharides; Polysaccharides; Scedosporium
PubMed: 32990888
DOI: 10.1007/s11046-020-00480-7 -
Cureus Sep 2023() is an increasingly prevalent and treatment-resistant opportunistic fungus. The pathogen is known to cause a variety of clinical manifestations ranging from localized...
() is an increasingly prevalent and treatment-resistant opportunistic fungus. The pathogen is known to cause a variety of clinical manifestations ranging from localized cutaneous disease to disseminated systemic infection. Herein we present an otherwise healthy 41-year-old male with biopsy-proven cutaneous infection. The patient experienced drastic clinical improvement on two months of a combination of oral itraconazole and oral minocycline. exhibits resistance to many antifungal agents, thus, single-agent antifungal therapy has a high failure rate and often results in the need for surgical excision or debridement. Recent accounts suggest that minocycline in combination with azole antifungals has a synergistic effect in treating . This case highlights the excellent response to combination oral therapies with minocycline and itraconazole. Prompt and efficacious treatment reduces the risk of destructive or disseminated disease and may avoid the need for surgical intervention.
PubMed: 37809133
DOI: 10.7759/cureus.44738 -
Antimicrobial Agents and Chemotherapy Sep 2022Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates....
EUCAST-Obtained Olorofim MICs against Aspergillus and Scedosporium Species and Lomentospora prolificans Showed High Agreements between Visual Inspection and Spectrophotometric Readings.
Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates. Here, we tested and compared the activity of a novel antifungal, olorofim, against Aspergillus spp., spp., and Lomentospora prolificans by visual inspection and spectrophotometric readings. Clinical isolates of Aspergillus ( = 686) and ( = 36) spp. and ( = 13) were tested. Olorofim MICs were evaluated-following the EUCAST E.Def 9.4 procedure-by visual inspection or spectrophotometric readings (combinations of either ≥90% or ≥95% fungal growth inhibition endpoints compared to drug-free control endpoints and different wavelengths [405 nm, 450 nm, 492 nm, 540 nm, and 620 nm]). We observed high activity of olorofim against all tested Aspergillus spp. (MICs up to 0.06 mg/L), except for A. calidoustus, and against and spp. (MICs up to 0.125 mg/L). The combination of ≥90% fungal growth inhibition endpoints at wavelengths of ≥492 nm resulted in high essential agreements with A. fumigatus and lesser agreement with non- Aspergillus, spp., and , although the number of isolates studied was low. This single-center study shows high agreement among olorofim MICs against A. fumigatus by visual inspection and spectrophotometric readings (≥90% fungal growth inhibition endpoints and wavelengths of ≥492 nm) and encouraging results against non- Aspergillus spp., spp., and .
Topics: Acetamides; Amphotericin B; Antifungal Agents; Aspergillus; Piperazines; Pyrimidines; Pyrroles; Scedosporium
PubMed: 35924916
DOI: 10.1128/aac.00849-22