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Clinical Microbiology and Infection :... Apr 2014Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in...
Mycoses summarized in the hyalohyphomycosis group are heterogeneous, defined by the presence of hyaline (non-dematiaceous) hyphae. The number of organisms implicated in hyalohyphomycosis is increasing and the most clinically important species belong to the genera Fusarium, Scedosporium, Acremonium, Scopulariopsis, Purpureocillium and Paecilomyces. Severely immunocompromised patients are particularly vulnerable to infection, and clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Diagnosis usually requires isolation and identification of the infecting pathogen. A poor prognosis is associated with fusariosis and early therapy of localized disease is important to prevent progression to a more aggressive or disseminated infection. Therapy should include voriconazole and surgical debridement where possible or posaconazole as salvage treatment. Voriconazole represents the first-line treatment of infections due to members of the genus Scedosporium. For Acremonium spp., Scopulariopsis spp., Purpureocillium spp. and Paecilomyces spp. the optimal antifungal treatment has not been established. Management usually consists of surgery and antifungal treatment, depending on the clinical presentation.
Topics: Antifungal Agents; Fusarium; Humans; Hyalohyphomycosis; Scedosporium
PubMed: 24548001
DOI: 10.1111/1469-0691.12465 -
Fungal Biology Jan 2014The filamentous fungus Scedosporium prolificans is an emerging multidrug resistant pathogen related to serious infections mainly affecting immunocompromised individuals....
The filamentous fungus Scedosporium prolificans is an emerging multidrug resistant pathogen related to serious infections mainly affecting immunocompromised individuals. Considering that it is frequently isolated from anthropic environments and penetrates mainly through the airways, the human mucosal immune system may play an important protective role against S. prolificans. To advance in the search for biomarkers and targets both for diagnosis and treatment, we analysed the S. prolificans immunomes recognized by human salivary Immunoglobulin A. Using indirect immunofluorescence, it was observed that conidia were strongly recognized, while hyphae were not. By 2-D immunoblotting and peptide mass fingerprinting, 25 immunodominant antigens in conidia and 30 in hyphae were identified. These included catalase, putative glyceronetransferase, translation elongation factor-1α, serine/threonine protein kinase, putative superoxide dismutase, putative mitochondrial cyclophilin 1 and peptidyl-prolyl cis-trans isomerase in conidiospores, and putative Hsp60, ATP synthase β chain, 40S ribosomal protein S0, citrate synthase and putative ATP synthase in hyphae. The functional study showed that metabolism - and protein fate - related enzymes were the most abundant antigens in conidia, whereas metabolism - , translation - , or energy production - related enzymes were in hyphae. The immunogenic proteins identified are proposed as candidates for the development of novel diagnostic tools or therapeutic strategies.
Topics: Antibodies, Fungal; Antigens, Fungal; Fluorescent Antibody Technique, Indirect; Humans; Hyphae; Immunoblotting; Immunodominant Epitopes; Immunoelectrophoresis, Two-Dimensional; Immunoglobulin A; Mass Spectrometry; Saliva; Scedosporium; Spores, Fungal
PubMed: 24433680
DOI: 10.1016/j.funbio.2013.11.006 -
The Spine Journal : Official Journal of... Sep 2009Postoperative fungal spondylodiscitis is a rare infectious disease. (Review)
Review
BACKGROUND CONTEXT
Postoperative fungal spondylodiscitis is a rare infectious disease.
PURPOSE
We report the first case of postoperative spondylodiscitis because of Scedosporium prolificans and review postoperative vertebral infection caused by fungi.
STUDY DESIGN/SETTING
Medline search.
METHODS
Case report and literature review.
RESULTS
On reviewing the cases of postoperative fungal spondylodiscitis reported so far in the literature, we found eight were caused by mold, and five by yeast. Clinically, the disease presents similar to postoperative vertebral osteomyelitis caused by bacteria, and a high clinical index of suspicion may be required to perform appropriate cultures to establish a diagnosis. Our review revealed a significant number of cases that were cured after surgical debridement and/or antifungal therapy.
CONCLUSIONS
On the basis of this limited assessment, it appears that the clinical course and prognosis of postoperative fungal spondylodiscitis is similar to that reported for postoperative pyogenic spondylodiscitis.
Topics: Anti-Bacterial Agents; Antifungal Agents; Arthrodesis; Debridement; Discitis; Female; Humans; Intervertebral Disc Displacement; Magnetic Resonance Imaging; Middle Aged; Mycoses; Orthopedic Procedures; Postoperative Complications; Pyrimidines; Scedosporium; Triazoles; Voriconazole
PubMed: 19447683
DOI: 10.1016/j.spinee.2009.03.012 -
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 -
Brazilian Journal of Microbiology :... Jun 2020Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still...
Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still largely unknown. In the present work, we have evaluated the interaction of S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans with lung epithelial cells (A549 line). The results showed that conidia were able to interact with A549 cells, displaying association indexes of 73.20, 117.98, 188.01, and 241.63 regarding S. apiospermum, L. prolificans, S. minutisporum, and S. aurantiacum, respectively. Light microscopy images evidenced morphological changes in epithelial cells, including rounding and detachment, especially during the interaction with L. prolificans. Plasma membrane injuries were detected in A549 cells after 1 h of co-culturing with S. aurantiacum and S. minutisporum and after 4 h with S. apiospermum and L. prolificans, as judged by the passive incorporation of propidium iodide. After 24 h of fungi-epithelial cells interaction, only mycelia were observed covering the A549 monolayer. Interestingly, the mycelial trap induced severe damage in the A549 cells, culminating in epithelial cell death. Our results demonstrate some relevant events that occur during the contact between lung epithelial cells and Scedosporium/Lomentospora species, including conidial adhesion and hyphal growth with consequent irreversible injury on A549 cells, adding light to the infection process caused by these opportunistic and multidrug-resistant fungi.
Topics: A549 Cells; Epithelial Cells; Host-Pathogen Interactions; Humans; Lung; Scedosporium; Spores, Fungal; Virulence
PubMed: 31736016
DOI: 10.1007/s42770-019-00183-2 -
The Journal of Antimicrobial... Dec 2020To evaluate the in vitro activity of olorofim, a new broad-spectrum antifungal with a novel mechanism of action, against a collection of 123 Spanish clinical isolates...
OBJECTIVES
To evaluate the in vitro activity of olorofim, a new broad-spectrum antifungal with a novel mechanism of action, against a collection of 123 Spanish clinical isolates belonging to five Scedosporium species and Lomentospora prolificans.
METHODS
The activity of olorofim against Scedosporium apiospermum (n = 30), Scedosporium boydii (n = 30), Scedosporium ellipsoideum (n = 10), Scedosporium aurantiacum (n = 20), Scedosporium dehoogii (n = 3) and Lomentospora prolificans (n = 30) was compared with that of amphotericin B, voriconazole, isavuconazole and micafungin by performing EUCAST and CLSI reference methods for antifungal susceptibility testing.
RESULTS
Amphotericin B and isavuconazole showed MICs ≥2 mg/L for all the species evaluated and voriconazole was moderately active (GM, MIC50 and MIC90 values ≤2 mg/L) against all of them except L. prolificans. Micafungin was effective against S. apiospermum complex strains, but exhibited elevated MECs for S. dehoogii and S. aurantiacum. Olorofim showed low MICs for all the Scedosporium strains tested (GM values were lower than 0.130 and 0.339 by the EUCAST method and the CLSI method, respectively, for all of the species), including those belonging to the MDR species L. prolificans, for which GM values were 0.115 and 0.225 mg/L by the EUCAST method and the CLSI method, respectively, while the GMs for the rest of the antifungals evaluated were higher than 3.732 mg/L using both methodologies.
CONCLUSIONS
Olorofim displayed promising in vitro activity against the Scedosporium and L. prolificans strains tested, some of which have reduced susceptibility to the antifungals that are currently in use.
Topics: Acetamides; Antifungal Agents; Microbial Sensitivity Tests; Piperazines; Pyrimidines; Pyrroles; Scedosporium
PubMed: 32856079
DOI: 10.1093/jac/dkaa351 -
The Journal of Antimicrobial... Jan 2024Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without...
BACKGROUND
Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without haematological malignancy. This study investigated excess index hospitalization costs and cumulative costs of these infections. The predictors of excess cost and length of stay (LOS) of index hospitalization were determined. These estimates serve as valuable inputs for cost-effectiveness models of novel antifungal agents.
METHODS
A retrospective case-control study was conducted at six Australian hospitals. Cases of proven/probable invasive Scedosporium/L. prolificans infections between 2011 and 2021 (n = 34) were matched with controls (n = 66) by predefined criteria. Cost data were retrieved from activity-based costing systems and analysis was performed from the Australian public hospital perspective. All costs were presented in 2022 Australian dollars (AUD). Median regression analysis was used to adjust excess costs of index hospitalization whereas cumulative costs up to 1.5 years follow-up were estimated using interval-partitioned survival probabilities.
RESULTS
Invasive Scedosporium/L. prolificans infections were independently associated with an adjusted median excess cost of AUD36 422 (P = 0.003) and LOS of 16.27 days (P < 0.001) during index hospitalization. Inpatient stay was the major cost driver (42.7%), followed by pharmacy cost, of which antifungal agents comprised 23.8% of the total cost. Allogeneic haematopoietic stem cell transplant increased the excess cost (P = 0.013) and prolonged LOS (P < 0.001) whereas inpatient death within ≤28 days reduced both cost (P = 0.001) and LOS (P < 0.001). The median cumulative cost increased substantially to AUD203 292 over 1.5 years in cases with Scedosporium/L. prolificans infections.
CONCLUSIONS
The economic burden associated with invasive Scedosporium/L. prolificans infections is substantial.
Topics: Humans; Antifungal Agents; Scedosporium; Case-Control Studies; Retrospective Studies; Australia
PubMed: 37944018
DOI: 10.1093/jac/dkad345 -
Mycopathologia Aug 2017We identified 11 Lomentospora prolificans isolates recovered from Mexican patients using phenotypic and molecular characteristics. The identification of isolates was...
We identified 11 Lomentospora prolificans isolates recovered from Mexican patients using phenotypic and molecular characteristics. The identification of isolates was assessed by internal transcribed spacer (ITS rDNA) sequencing. In vitro susceptibility to amphotericin B, fluconazole, voriconazole, posaconazole, caspofungin, anidulafungin and micafungin was determined according to Clinical and Laboratory Standards Institute (CLSI) procedures. Three isolates (07-2239, 11-2242 and 04-2673) were used to induce systemic infection in immunocompetent ICR mice. Survival and tissue burden studies were used as markers of pathogenicity. All of the strains were resistant to every antifungal tested with MIC's for AmB (8->8 µg/ml), VRC (16->16 µg/ml), PSC (16->16 µg/ml), FLC (64->64 µg/ml) and echinocandins with MICs ≥8 µg/ml. One hundred, ninety and sixty percent of the infected mice with the strains 07-2239, 11-2242 and 04-2673 died during the study, respectively. Regarding tissue burden, the highest fungal load of the infected mice was detected in brain followed by spleen and kidney, regardless of the strain.
Topics: Adolescent; Adult; Aged; Animal Structures; Animals; Antifungal Agents; Child; Cluster Analysis; Colony Count, Microbial; DNA, Fungal; DNA, Ribosomal Spacer; Disease Models, Animal; Female; Humans; Male; Mexico; Mice, Inbred ICR; Microbial Sensitivity Tests; Middle Aged; Mycoses; Phylogeny; Scedosporium; Sequence Analysis, DNA; Survival Analysis
PubMed: 28456868
DOI: 10.1007/s11046-017-0137-5 -
Enfermedades Infecciosas Y... 2001Scedosporium prolificans is a dematiaceous fungus that is known to cause a wide spectrum of infections in humans, bearing a severity and a prognosis that is relationed... (Comparative Study)
Comparative Study Review
BACKGROUND
Scedosporium prolificans is a dematiaceous fungus that is known to cause a wide spectrum of infections in humans, bearing a severity and a prognosis that is relationed with the patients immune status.
METHODS
A retrospective review was made of the clinical charts of all patients who developed positive S. prolificans cultures in our centre from 1990 to 2000. Isolates were identified by colonial morphology and microscopic features. The in vitro susceptibility was evaluated using the microdilution method according to NCCLS.
RESULTS
S. prolificans was isolated in 15 patients. Eight were affected with cystic fibrosis and the isolation of S. prolificans in their airways did not worsen their clinical status. Among the remaining 7 cases there were five leukemic patients with neutropenia and two immunocompetent hosts with cutaneous infection and endocarditis. Four of five neutropenic patients died of sudden sepsis and S. prolificans was isolated from blood cultures made a few days before their death, and the fifth neutropenic case suffered a bilateral pneumonia with improving course probably due to recovery from neutropenia. As to the immunocompetent group the clinical course was good in the cutaneous infection case, but the endocarditis case died four days after the antifungical therapy was started. All the isolates tested were found to be resistant to amphotericin, 5 flucytosine, fluconazole, itraconazole, voriconazole, miconazole and terbinafine.
CONCLUSIONS
Scedosporium prolificans is a fungal pathogen that colonizes the airways of patients affected with cystic fibrosis. It can also cause a wide variety of infections, whose severity and prognosis depends on the patients immune status. Due to the resistance of this fungus to antifungal drugs, the therapeutic options are limited. Only with the correction of neutropenia and surgery in local infections in immunocompetent hosts it has been possible to cure these infections.
Topics: Acute Disease; Adolescent; Adult; Aged; Antifungal Agents; Child, Preschool; Cystic Fibrosis; Disease Susceptibility; Drug Resistance, Multiple, Fungal; Endocarditis; Female; Humans; Immunocompetence; Infant; Infant, Newborn; Leukemia, Myeloid; Male; Middle Aged; Mycetoma; Neutropenia; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Scedosporium; Spain; Wound Infection
PubMed: 11747789
DOI: 10.1016/s0213-005x(01)72651-1 -
Memorias Do Instituto Oswaldo Cruz 2018BACKGROUND Scedosporium/Lomentospora species are opportunistic mould pathogens, presenting notable antifungal resistance. OBJECTIVES/METHODS We analysed the conidia and... (Comparative Study)
Comparative Study
Scedosporium apiospermum, Scedosporium aurantiacum, Scedosporium minutisporum and Lomentospora prolificans: a comparative study of surface molecules produced by conidial and germinated conidial cells.
BACKGROUND Scedosporium/Lomentospora species are opportunistic mould pathogens, presenting notable antifungal resistance. OBJECTIVES/METHODS We analysed the conidia and germinated conidia of S. apiospermum (Sap), S. aurantiacum (Sau), S. minutisporum (Smi) and L. prolificans (Lpr) by scanning electron microscopy and exposition of surface molecules by fluorescence microscopy. FINDINGS Conidia of Sap, Smi and Sau had oval, ellipsoidal and cylindrical shape, respectively, with several irregularities surrounding all surface areas, whereas Lpr conidia were rounded with a smooth surface. The germination of Sap occurred at the conidial bottom, while Smi and Sau germination primarily occurred at the centre of the conidial cell, and Lpr germination initiated at any part of the conidial surface. The staining of N-acetylglucosamine-containing molecules by fluorescein-labelled WGA primarily occurred during the germination of all studied fungi and in the conidial scars, which is the primary location of germination. Calcofluor white, which recognises the polysaccharide chitin, strongly stained the conidial cells and, to a lesser extent, the germination. Both mannose-rich glycoconjugates (evidenced by fluoresceinated-ConA) and cell wall externally located polypeptides presented distinct surface locations and expression according to both morphotypes and fungal species. In contrast, sialic acid and galactose-containing structures were not detected at fungal surfaces. MAIN CONCLUSIONS The present study demonstrated the differential production/exposition of surface molecules on distinct morphotypes of Scedosporium/Lomentospora species.
Topics: Cell Differentiation; Cell Membrane; Microscopy, Electron, Scanning; Microscopy, Fluorescence; Scedosporium; Spores, Fungal
PubMed: 29924142
DOI: 10.1590/0074-02760180102