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The Journal of Antimicrobial... Jul 2017Scedosporium species and Lomentospora prolificans are increasing causes of invasive infections in immunocompromised hosts and many isolates are resistant to available...
BACKGROUND
Scedosporium species and Lomentospora prolificans are increasing causes of invasive infections in immunocompromised hosts and many isolates are resistant to available antifungals. Our objective was to assess the in vitro potency of F901318, a member of the orotomide class of antifungals, against Scedosporium species and L. prolificans .
METHODS
The in vitro potency of F901318 was evaluated against 66 Scedosporium and 7 L. prolificans clinical isolates using the CLSI M38-A2 reference standard. Scedosporium species included Scedosporium apiospermum ( n = 43), Scedosporium aurantiacum ( n = 6), Scedosporium dehoogii ( n = 2) and Scedosporium boydii ( n = 15). Positive comparators included amphotericin B, caspofungin, posaconazole and voriconazole.
RESULTS
Against S. apiospermum and S. boydii F901318 geometric mean MICs/MECs (0.079 and 0.046 mg/L, respectively) were significantly lower than those observed with amphotericin (3.404 and 5.595 mg/L), posaconazole (1.937 and 1.823 mg/L), voriconazole (0.784 and 0.630 mg/L) and caspofungin (5.703 and 7.639 mg/L) ( P < 0.001). Against S. aurantiacum and S. dehoogii the F901318 MIC range (0.12-0.5 mg/L) was also lower than those for the other antifungals (0.5 to >8 mg/L). F901318 also maintained activity against L. prolificans isolates (range 0.12-0.25 mg/L) in contrast to other antifungals, of which none demonstrated in vitro activity.
CONCLUSIONS
F901318 demonstrated potent in vitro activity against Scedosporium species and L. prolificans . This activity was maintained against isolates that had significantly reduced susceptibility to the other antifungals. Further studies are warranted to evaluate the in vivo efficacy of F901318 against Scedosporium species and L. prolificans .
Topics: Antifungal Agents; Ascomycota; Caspofungin; Dihydroorotate Dehydrogenase; Echinocandins; Humans; Lipopeptides; Microbial Sensitivity Tests; Mycoses; Oxidoreductases Acting on CH-CH Group Donors; Scedosporium; Triazoles; Voriconazole
PubMed: 28333310
DOI: 10.1093/jac/dkx065 -
Critical Reviews in Microbiology Feb 2019Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in immunocompromised and occasionally in healthy hosts. Scedosporium spp. is...
Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive diagnostic workup and even more for new, effective antifungal drugs to improve patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp. and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScope registry. For 208 Scedosporium spp. infections solid organ transplantation (n = 58, 27.9%) and for 56 L. prolificans infection underlying malignancy (n = 28, 50.0%) were the most prevalent risk factors. L. prolificans infections frequently presented as fungemia (n = 26, 46.4% versus n = 12, 5.8% for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better overall outcome in both groups compared to treatment with amphotericin B formulations. This review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and investigational antifungals, and treatment strategies of severe infections caused by Scedosporium spp. and L. prolificans.
Topics: Adult; Aged; Antifungal Agents; Female; Humans; Immunocompromised Host; Invasive Fungal Infections; Male; Middle Aged; Neoplasms; Organ Transplantation; Prognosis; Risk Factors; Scedosporium; Survival Analysis; Treatment Outcome; Voriconazole
PubMed: 30628529
DOI: 10.1080/1040841X.2018.1514366 -
Mycopathologia Feb 2018The genus Scedosporium, which comprises at least five clinically relevant species, i.e. Scedosporium apiospermum, Scedosporium boydii, Scedosporium aurantiacum,... (Review)
Review
The genus Scedosporium, which comprises at least five clinically relevant species, i.e. Scedosporium apiospermum, Scedosporium boydii, Scedosporium aurantiacum, Scedosporium dehoogii and Scedosporium minutisporum, ranks the second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). This colonization of the airways is thought to contribute to the inflammatory reaction leading to a progressive deterioration of the lung function. Additionally, these colonizing fungi may lead to severe disseminated infections in case of lung transplantation. Therefore, considering the low susceptibility of Scedosporium species to all current antifungal drugs, preventive measures should be defined to reduce the risk of exposure to these fungi for non-colonized CF patients. With this in mind, several studies have been conducted to elucidate the ecology of these fungi and to define possible sources of patient contamination. This review will summarize the major outcomes of those studies, including: the clear demonstration that ecological niches of Scedosporium species are strongly impacted by human activities, and the ability of Scedosporium species to degrade aliphatic and aromatic pollutants which supports the high occurrence of these species in contaminated soils and polluted waters and makes them promising candidates for bioremediation purposes. Finally, prospects for future research in this field are proposed.
Topics: Cystic Fibrosis; Environmental Exposure; Humans; Lung Diseases, Fungal; Scedosporium
PubMed: 28929280
DOI: 10.1007/s11046-017-0200-2 -
Internal Medicine (Tokyo, Japan) Sep 2023
Topics: Humans; Scedosporium; Antifungal Agents
PubMed: 36642520
DOI: 10.2169/internalmedicine.1074-22 -
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 -
Clinical Microbiology Reviews Jan 2008Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide... (Review)
Review
Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.
Topics: Administration, Inhalation; Animals; Antifungal Agents; Arthritis; Biodiversity; Bone Diseases, Infectious; Central Nervous System Fungal Infections; Eye Infections, Fungal; Humans; Immunocompromised Host; Immunosuppressive Agents; Microbial Sensitivity Tests; Mycetoma; Phylogeny; Respiratory Tract Infections; Scedosporium
PubMed: 18202441
DOI: 10.1128/CMR.00039-07 -
Medical Mycology Nov 2010Several Scedosporium species are clinically important emerging pathogens. Scedosporium prolificans is reported to be the most virulent of the species, while the recently...
Several Scedosporium species are clinically important emerging pathogens. Scedosporium prolificans is reported to be the most virulent of the species, while the recently described species Scedosporium aurantiacum, which accounts for a substantial proportion of Australian clinical isolates is capable of causing a range of serious infections. In addition, environmental surveys have revealed a high prevalence of S. aurantiacum in the urban Sydney region. This study was conducted to assess the virulence of selected S. aurantiacum strains recovered from patients who are colonized or have invasive disease, as well as those from environmental sources, in comparison with S. prolificans. PCR fingerprinting with the primer M13 revealed high genetic variation among the S. aurantiacum strains. We evaluated the virulence of eight S. aurantiacum and two S. prolificans strains in a murine model using an infectious dose of 2 × 10⁵ conidia. S. aurantiacum was noted to be as virulent as S. prolificans, causing death in 60-100% of mice (P > 0.05). There were significant strain-specific virulence differences (P < 0.005), indicating a possible link between genotype and virulence in S. aurantiacum.
Topics: Animals; DNA Fingerprinting; Disease Models, Animal; Female; Genotype; Humans; Mice; Mice, Inbred BALB C; Mycetoma; Scedosporium; Species Specificity; Virulence
PubMed: 21067330
DOI: 10.3109/13693786.2010.517224 -
Antimicrobial Agents and Chemotherapy Oct 2015N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against...
N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against Scedosporium and Lomentospora, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans (formerly Scedosporium prolificans) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1- to 4-log10 reduction in CFU after 4 h and a 4- to >6-log10 reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of Galleria mellonella infected with 1.0 × 10(7) conidia of S. apiospermum and S. boydii died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different Scedosporium and Lomentospora species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.
Topics: Ammonium Chloride; Animals; Anti-Infective Agents, Local; Antifungal Agents; Cell Membrane; Cell Membrane Permeability; Cell Wall; Chloramines; Hyphae; Larva; Microbial Sensitivity Tests; Moths; Scedosporium; Spores, Fungal; Taurine
PubMed: 26239996
DOI: 10.1128/AAC.00957-15 -
Transplantation Proceedings May 2021Infections caused by the Scedosporium genus have become recognized as a fatal complication after lung transplantation in Europe and Australia, but the reports have been...
Infections caused by the Scedosporium genus have become recognized as a fatal complication after lung transplantation in Europe and Australia, but the reports have been rare from Asian countries including Japan. We present a case of pneumonia caused by a mixed infection of Scedosporium apiospermum (SA) and Lomentospora prolificans (LP) that developed after augmentation of immunosuppression for chronic lung allograft dysfunction (CLAD) after lung transplantation. A 13-year-old man underwent bilateral lung transplantation for pulmonary hypertension. One year after surgery, he was treated with a series of augmented immunosuppressive therapy for severe acute rejection and subsequent CLAD. Three months following the first steroid pulse therapy, his serum β-D-glucan elevated without any sign of fungal infection by other tests. The serum β-D-glucan once returned to a normal level by empirical administration of micafungin; however, the patient's condition worsened again by discontinuation of it. He did not recover by restarting micafungin, and computed tomography (CT) scans eventually demonstrated new infiltrates in his lung field 6 weeks after the elevation of serum β-D-glucan. Microscopic findings of transbronchial lung biopsy specimens showed filamentous fungi, and the culture of bronchoalveolar lavage fluid revealed the growth of SA and LP. Despite subsequent voriconazole administration, he died 14 days after the start of voriconazole. Early and aggressive inspection including bronchoscopy should be performed for the diagnosis of Scedosporium infection in immunocompromised patients, even if CT scans and sputum culture show no evidence of infection.
Topics: Adolescent; Bronchoalveolar Lavage Fluid; Forced Expiratory Volume; Humans; Hypertension, Pulmonary; Immunocompromised Host; Invasive Fungal Infections; Lung Transplantation; Male; Pneumonia; Scedosporium; Thorax; Tomography, X-Ray Computed; beta-Glucans
PubMed: 33707042
DOI: 10.1016/j.transproceed.2021.02.002 -
Transplant Infectious Disease : An... Oct 2019Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients.
Perspectives on Scedosporium species and Lomentospora prolificans in lung transplantation: Results of an international practice survey from ESCMID fungal infection study group and study group for infections in compromised hosts, and European Confederation of Medical Mycology.
BACKGROUND
Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients.
METHODS
We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017.
RESULTS
A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years.
CONCLUSIONS
This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.
Topics: Ascomycota; Disease Management; Humans; Immunocompromised Host; Internationality; Lung Transplantation; Mycoses; Prospective Studies; Respiratory Tract Infections; Scedosporium; Surveys and Questionnaires
PubMed: 31283872
DOI: 10.1111/tid.13141