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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 -
Journal of Fungi (Basel, Switzerland) Jun 2018Species of and are considered emerging opportunistic pathogens, causing invasive fungal diseases in humans that are known as scedosporiosis and fusariosis,... (Review)
Review
Species of and are considered emerging opportunistic pathogens, causing invasive fungal diseases in humans that are known as scedosporiosis and fusariosis, respectively. These mold infections typically affect patients with immune impairment; however, cases have been reported in otherwise healthy individuals. Clinical manifestations vary considerably, ranging from isolated superficial infection to deep-seated invasive infection—affecting multiple organs—which is often lethal. While there have been a number of advances in the detection of these infections, including the use of polymerase chain reaction (PCR) and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS), diagnosis is often delayed, leading to substantial morbidity and mortality. Although the optimal therapy is controversial, there have also been notable advances in the treatment of these diseases, which often depend on a combination of antifungal therapy, reversal of immunosuppression, and in some cases, surgical resection. In this paper, we review these advances and examine how the management of scedosporiosis and fusariosis may change in the near future.
PubMed: 29912161
DOI: 10.3390/jof4020073 -
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 -
Journal of Fungi (Basel, Switzerland) Jan 2021/ fungi are increasingly recognized pathogens. As these fungi are resistant to many antifungal agents, early diagnosis is essential for initiating targeted drug therapy.... (Review)
Review
/ fungi are increasingly recognized pathogens. As these fungi are resistant to many antifungal agents, early diagnosis is essential for initiating targeted drug therapy. Here, we review the microbiological tools for the detection and diagnosis of invasive scedosporiosis and lomentosporiosis. Of over 10 species, , , and cause the majority of infections. Definitive diagnosis relies on one or more of visualization, isolation or detection of the fungus from clinical specimens by microscopy techniques, culture and molecular methods such as panfungal PCR or genus-/species-specific multiplex PCR. For isolation from respiratory tract specimens, selective media have shown improved isolation rates. Species identification is achieved by macroscopic and microscopic examination of colonies, but species should be confirmed by ITS with or without β-tubulin gene sequencing or other molecular methods. Matrix-assisted laser desorption ionization-time of flight mass spectrometry databases are improving but may need supplementation by in-house spectra for species identification. Reference broth microdilution methods is preferred for antifungal susceptibility testing. Next-generation sequencing technologies have good potential for characterization of these pathogens. Diagnosis of / infections relies on multiple approaches encompassing both phenotypic- and molecular-based methods.
PubMed: 33406673
DOI: 10.3390/jof7010023 -
Frontiers in Microbiology 2021Lignin, a natural polyaromatic macromolecule, represents an essential component of the lignocellulose biomass. Due to its complexity, the natural degradation of this...
Lignin, a natural polyaromatic macromolecule, represents an essential component of the lignocellulose biomass. Due to its complexity, the natural degradation of this molecule by microorganisms still remains largely misunderstood. Extracellular oxidative degradation is followed by intracellular metabolic degradation of conserved aromatic intermediate compounds (protocatechuate, catechol, hydroxyquinol, and gentisic acid) that are used as carbon and energy sources. The lower funneling pathways are characterized by the opening of the aromatic ring of these molecules through dioxygenases, leading to degradation products that finally enter into the tricarboxylic acid (TCA) cycle. In order to better understand the adaptation mechanisms of species to their environment, these specific catabolism pathways were studied. Genes encoding ring-cleaving dioxygenases were identified in genomes by sequence homology, and a bioinformatic analysis of the organization of the corresponding gene clusters was performed. In addition, these predictions were confirmed by evaluation of the expression level of the genes of the gentisic acid cluster. When the fungus was cultivated in the presence of lignin or gentisic acid as sole carbon source, experiments revealed that the genes of the gentisic acid cluster were markedly overexpressed in the two species analyzed ( and ). Only the gene encoding a membrane transporter was not overexpressed in the gentisic acid-containing medium. Together, these data suggest the involvement of the lower funneling pathways in adaptation to their environment.
PubMed: 34276578
DOI: 10.3389/fmicb.2021.630753 -
Acta Tropica Jan 2022Mycetoma is a chronic granulomatous inflammatory disease that is caused either by bacteria or fungi. Bacterial mycetoma (actinomycetoma) can be caused by various... (Review)
Review
Mycetoma is a chronic granulomatous inflammatory disease that is caused either by bacteria or fungi. Bacterial mycetoma (actinomycetoma) can be caused by various causative agents of the genera Nocardia, Streptomyces and Actinomadura. On the other hand, fungal mycetoma (eumycetoma) is most commonly caused by causative agents belonging to the genera Madurella, Scedosporium and Falciformispora. Early and accurate diagnosis of the causative organisms can guide proper patient management and treatment. To allow rapid and accurate species identification, different molecular techniques were developed over the past decades. These techniques can be protein based (MALDI-TOF MS) as well as DNA based (Sequencing, PCR and isothermal amplification methods). In this review, we provide an overview of the different molecular techniques currently in use and identify knowledge gaps, which need to be addressed before we can implement molecular diagnostics for mycetoma in different clinical settings.
Topics: Fungi; Humans; Madurella; Mycetoma; Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 34687643
DOI: 10.1016/j.actatropica.2021.106205 -
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 -
Scientific Reports Feb 2019The opportunistic pathogen Mycobacterium ulcerans, which is responsible for Buruli ulcer, synthesizes a series of plasmid-encoded macrolide exotoxins termed...
The opportunistic pathogen Mycobacterium ulcerans, which is responsible for Buruli ulcer, synthesizes a series of plasmid-encoded macrolide exotoxins termed mycolactones. These toxins destabilize cell membranes and induce apoptosis-associated pleiotropic effects including tissue destruction, analgesic and anti-inflammatory effects. Despite its medical interest, M. ulcerans is primarily an environmental mycobacterium and the primary functions of mycolactones in the natural ecosystems are unknown. High throughput biochemical profiling findings suggested that M. ulcerans may interact with fungi. Here, we report that semi-purified and purified mycolactones significantly enhance spore germination of Scedosporium apiospermum, Fusarium equiseti and Mucor circinelloides; and that M. ulcerans mycolactones significantly attract colonies of M. circinelloides whereas no significant effect was observed on S. apiospermum and F. equiseti. These experimental results suggest that mycolactones exhibit a chemoattractant activity independent of their cytotoxicity. In natural ecosystems, M. ulcerans mycolactones may act as spore germination inducers and chemoattractants for some fungi, suggesting a novel role for this unique class of mycobacterial toxins in natural ecosystems.
Topics: Apoptosis; Ecosystem; Exotoxins; Fungi; Humans; Macrolides; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans
PubMed: 30816261
DOI: 10.1038/s41598-019-39927-3 -
Current Fungal Infection Reports 2016Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and... (Review)
Review
Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and intravenous formulation with improved pharmacokinetic properties have been introduced recently. Due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions, therapeutic drug monitoring (TDM) is advised to ensure adequate exposure and improve clinical response for posaconazole. Here, we highlight and discuss the most recent findings on pharmacokinetics and pharmacodynamics of posaconazole in the setting of prophylaxis and treatment of fungal infections and refer to the challenges associated with TDM of posaconazole.
PubMed: 27358662
DOI: 10.1007/s12281-016-0255-4 -
Pathogens (Basel, Switzerland) May 2023Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of... (Review)
Review
Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of chronic lung allograft dysfunction. Prompt diagnosis and treatment are imperative to limit allograft damage. This review article discusses incidence, risk factors, and symptoms with a specific focus on diagnostic and treatment strategies in the lung transplant population for fungal infections caused by , , , , , , , and . Evidence for the use of newer triazole and inhaled antifungals to treat isolated pulmonary fungal infections in lung transplant recipients is also discussed.
PubMed: 37242364
DOI: 10.3390/pathogens12050694