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Lomentospora prolificans has caused outbreaks in immunocompromised patients. We performed whole genome sequencing (WGS) on 4 L. prolificans isolates from infections occurring during an 8-month period in the haematology unit at Hospital 1., and 2 isolates from unrelated infections at Hospital 2., showing a high number of mutational differences (>10,000 single nucleotide polymorphisms) between L. prolificans isolates from Hospital 1. Novel typing of isolates by WGS did not demonstrate a single causative strain.

Lomentospora prolificans has caused outbreaks in immunocompromised patients. We performed whole genome sequencing (WGS) on 4 L. prolificans isolates from infections occurring during an 8-month period in the haematology unit at Hospital 1., and 2 isolates from unrelated infections at Hospital 2., showing a high number of mutational differences (>10,000 single nucleotide polymorphisms) between L. prolificans isolates from Hospital 1. Novel typing of isolates by WGS did not demonstrate a single causative strain. [ABSTRACT FROM AUTHOR]

Voriconazole Cmin remained suboptimal despite adequate treatment compliance and absence of any drug-drug interactions with a cytochrome P450 (CYP) inducer. Drug interactions should be avoided in most treatments because of the risk of failure or toxicity but may be used as a modulating factor of drug pharmacokinetics in association with therapeutic drug monitoring in specific cases. [Extracted from the article]

One hundred clinical isolates from a prospective nationwide study of scedosporiosis in Australia (2003–2005) and 46 additional isolates were genotyped by internal transcribed spacer–restriction fragment length polymorphism (ITS-RFLP) analysis, ITS sequencing, and M13 PCR fingerprinting. ITS-RFLP and PCR fingerprinting identified 3 distinct genetic groups. The first group corresponded to Scedosporium prolificans (n = 83), and the other 2 comprised isolates previously identified as S. apiospermum: one of these corresponded to S. apiospermum (n = 33) and the other to the newly described species S. aurantiacum (n = 30). Intraspecies variation was highest for S. apiospermum (58%), followed by S. prolificans (45%) and S. aurantiacum (28%) as determined by PCR fingerprinting. ITS sequence variation of 2.2% was observed among S. apiospermum isolates. No correlation was found between genotype of strains and their geographic origin, body site from which they were cultured, or colonization versus invasive disease. Twelve S. prolificans isolates from 2 suspected case clusters were examined by amplified fragment length polymorphism analysis. No specific clusters were confirmed.

Central nervous system lomentosporiosis is a rare pathological condition in immunocompromised patients. We describe a fatal case of meningitis caused by Lomentospora prolificans (which was previously named Scedosporium prolificans), after an allogeneic hematopoietic stem cell transplantation (allo- HSCT). To our knowledge, no cases of Lomentospora meningitis following allo- HSCT have been reported previously. Particularly in neutropenic patients, it is important to consider L. prolificans when a fungal infection is suspected and antifungal agents are ineffective. [ABSTRACT FROM AUTHOR]

Background: Lomentospora prolificans (formally Scedosporium prolificans) is an environmental mould with a global distribution. Endocarditis caused by L. prolificans is a rare but serious emerging disease in immunocompromised patients. Prior to this case there have only been eight cases reported in the literature. Diagnosis can be challenging and there are no evidence-based guidelines for treatment.Case Presentation: We report a 75-year-old woman with ovarian carcinoma who presented with fever after chemotherapy. Repeated sterile site cultures remained negative until day 22 of admission, when Lomentospora prolificans was isolated from blood cultures. Following extensive investigations, including Fluoro-D-glucose positron emission tomography (FDG-PET) and transoephageal echocardiography (TOE), the patient was diagnosed with endocarditis complicated by cerebral emboli. The patient was considered unsuitable for surgical intervention and passed away five days after the fungus was isolated.Conclusion: Endocarditis caused by Lomentospora prolificans is a rare but emerging condition, with limited treatment options and a high mortality. Awareness of the increasing incidence of Lomentospora prolificans infection, diagnosed often at an advanced stage, with potential for endocarditis may prompt earlier echocardiography or FDG-PET imaging. Further studies are needed to determine the optimal combination and duration of anti-fungal agents, used in conjunction with aggressive surgical excision where feasible. [ABSTRACT FROM AUTHOR]

We describe a case of keratitis with acute presentation and without any history of trauma caused by Scedosporium prolificans; a rare cause of fungal keratitis, from a tertiary care hospital. To the best of our knowledge this is the first such case reported from the region. Because of early diagnosis and prompt treatment the patient could be managed well.

Disseminated Scedosporium prolificans infection occurs mainly in immunocompromised patients. The mortality rate is high, as the fungus is resistant to most antifungal agents. Here, we present the case of a 66-year-old female with acute myeloid leukemia who developed infective endocarditis caused by S. prolificans infection during induction chemotherapy. Her 1,3-β-D-glucan levels were elevated and computed tomography revealed bilateral sinusitis and disseminated small nodular masses within the lungs and spleen; it nonetheless took 6 days to identify S. prolificans by blood culture. The patient died of multi-organ failure despite the combined use of voriconazole and terbinafine. Autopsy revealed numerous mycotic emboli within multiple organs (caused by mitral valve vegetation) and endocarditis (caused by S. prolificans). The geographic distribution of this infection is limited to Australia, the United States, and southern Europe, particularly Spain. The first Japanese case was reported in 2011, and four cases have been reported to date, including this one. Recently, the incidence of S. prolificans-disseminated infection in immunocompromised patients has increased in Japan. Therefore, clinicians should consider S. prolificans infection as a differential diagnosis when immunocompromised patients suffer disseminated infections with elevated 1,3-β-D-glucan levels. [ABSTRACT FROM AUTHOR]

Scedosporium prolificans (S. prolificans) is a type of mold, which rarely affects immunocompromised people. We treated a 71 - year-old woman with acute myeloid leukemia (AML-M5a) with low-dose cytarabine, acralubicin, and filgrastim as the induction therapy. On day 7 after the initiation of chemotherapy, she became febrile and agranulocytic, and developed anal pain; therefore, we discontinued the chemotherapy on day 8. Broad-spectrum antibiotics, micafungin, and then liposomal amphotericin B were ineffective. The serum concentration of β-D-glucan was 525 pg/mL. She died of multiple organ failure on day 17. S. prolificans was detected from the blood culture on day 13. Physicians should consider Scedosporium spp. infection when principal antifungal agents are ineffective and fungal infection is strongly suspected. [ABSTRACT FROM AUTHOR]

We report a case of non-fatal disseminated Scedosporium prolificans infection, including central nervous system disease and endophthalmitis, in a relapsed acute myeloid leukaemia patient with extensive CYP2C19 metabolism. Successful treatment required aggressive surgical debridement, three times daily voriconazole dosing and cimetidine CYP2C19 inhibition. In addition, the unique use of miltefosine was employed due to azole-chemotherapeutic drug interactions. Prolonged survival following disseminated S. prolificans, adjunctive miltefosine and augmentation of voriconazole exposure with cimetidine CYP2C19 inhibition has not been reported. [ABSTRACT FROM AUTHOR]

Abstract: Scedosporium prolificans are opportunistic moulds that can cause mycetoma following penetrating injuries. This fungus is more virulent than other species and treatment options are limited. Here we describe the first known case in the UK of S. prolificans osteomyelitis, in a 4 year old following penetrating injury. Successful outcome with limb salvage and foot function is achieved after repeated surgical debridement, and combination chemotherapy with voriconazole/terbinafine. [Copyright &y& Elsevier]

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Abstract: Scedosporium prolificans is an opportunistic saprophytic fungus that rapidly disseminates and is intrinsically resistant to currently available antifungal drugs. We report a fatal case of disseminated S. prolificans infection that started with orbital and ocular involvement in a patient with secondary acute myeloblastic leukemia. [Copyright &y& Elsevier]

Despite the adoption of antifungal prophylaxis, fungal infections remain a significant concern in lung transplant recipients. Indeed, some concern exists that such prophylaxis may increase the risk of infection with drug-resistant fungal organisms. Here, we describe a case of disseminated Scedosporium prolificans infection, presenting as pericarditis, which developed in a lung transplant patient receiving prophylactic voriconazole for 8 months. The epidemiology and clinical presentation of S. prolificans infections are reviewed, and controversies surrounding antifungal prophylaxis and the development of resistant infections are discussed. [ABSTRACT FROM AUTHOR]

Abstract: We report a case of Scedosporium prolificans infection in a patient following surgery for squamous cell lung carcinoma. Combination therapy with voriconazole and terbinafine was commenced for intrathoracic infection and mycotic vasculitis. In spite of antifungal treatment, he developed culture-positive sternal and rib osteomyelitis four months later. Scedosporiosis is not commonly reported in patients with solid organ malignancies, and this case highlights its aggressive nature and propensity for direct local invasion. [Copyright &y& Elsevier]

Copyright of Revista Iberoamericana de Micologia is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Breakthrough non-Aspergillus mold infections among patients receiving the anti-mold azole antifungal agents like voriconazole or posaconazole have been increasingly reported. We report a case of lung Scedosporium prolificans infection with multiple cavities in a 58-year-old man with monoclonal gammopathy of undetermined significance (MGUS) during voriconazole treatment for probable invasive aspergiIlosis. Cultures of repeated sputum specimens yielded the same fungus until his death 83 days after diagnosis. S. prolificans should be considered in patients with breakthrough infections receiving voriconazole. [ABSTRACT FROM AUTHOR]

Abstract: Hot aqueous extraction of conidia of Scedosporium prolificans gave a heterogeneous glycoprotein (RMP-Sp-Coni) with 41% protein and 2MeRha, Rha, Ara, Man, Gal, Glc, and GlcNH2 in a 2:18:3:47:9:15:6M ratio, the first report of 2-O-methylrhamnose in fungi. Methylation analysis showed nonreducing end- (10%), 2-O- (11%), and 3-O-substituted Rhap (7%), nonreducing end- (8%), 2-O- (12%), 3-O- (16%), and 2,6-di-O-substituted Manp (9%), nonreducing end- (4%), 3-O- (7%), and 4-O-substituted Glcp (7%), and nonreducing end-units of Galp (9%). Mild reductive β-elimination of RMP-Sp-Coni cleaved O-linked structures to give a mixture of oligosaccharides, of which 2MeRha capping groups were present in 2MeRhaRha2Hex2Hex-ol, 2MeRhaRha2Hex-Hex-ol, 2MeRhaRha2HexHex-ol, and 2MeRhaRha2Hex-ol (ESI-MS–MS). The mixture was fractionated by Biogel P-2 column chromatography and the two predominant isolates were β-d-Galp-(1→6)-[2Me-α-l-Rhap-(1→3)-α-l-Rhap-(1→3)-α-d-Manp-(1→2)]-d-Man-ol, and another lacking the β-Galp unit. Neither was formed from mycelial glycoprotein, although β-d-Galp-(1→6)-[α-l-Rhap-(1→3)-α-l-Rhap-(1→3)-α-d-Manp-(1→2)]-d-Man-ol was a common component. [Copyright &y& Elsevier]

Scedosporium prolificans is a truly emerging fungal pathogen. It has only been recognized as a human pathogen for 22 years and has been related with numerous infections in immunocompromised and immunocompetent patients. A search for cases in the literature was performed and a database was constructed. Cases were reviewed in order to analyse the epidemiology and outcome of infection. A total of 162 cases were included. The median age of patients was 45 years (ranging from a few months to 81 years), and 102 (63%) infections were diagnosed in males. Risk factors for scedosporiosis were malignancy, 74/162 (45.7%), cystic fibrosis, 19/172 (11.7%), and solid organ transplantation 14/162 (8.6%). The most common clinical presentations were disseminated infection, 72/162 cases (44.4%), pulmonary mycosis, 47/162 (29%), and bone and joint infections, 17/162 (10.4%). All disseminated infections afflicted patents with underlying diseases, primarily haematological malignancies (57/72 [80%]). Blood cultures were positive in 70% of patients suffering from disseminated mycosis. Neutropenia, fever and cerebral symptoms were independently related to the development of disseminated infection whereas recovery from aplasia was associated with a reduced risk. The overall mortality was 46.9% but mortality rate was 87.5% in patients with disseminated disease. Survival was independently associated with surgical excision and recovery from aplasia. Antifungal treatments were not related to a reduced risk of death. Infections caused by S. prolificans are life threatening in susceptible patients, and can be considered a truly emerging disease. Infections are difficult to treat since it is a multi-resistant species. Multicenter studies are essential with the aim of developing and disseminating appropriate techniques and protocols to treat this mycosis. [ABSTRACT FROM AUTHOR]

Scedosporium prolificans is one of the most life-threatening fungal opportunistic pathogens due to its high resistance to common systemic antifungal agents. While a close relative of Pseudallescheria boydii, S. prolificans has a more limited geographic range being primarily found in Australia, USA and Spain. Infections have also been reported from several other European countries and from Chile. Twenty patients with Scedosporium prolificans infection or colonization from August 1993 to May 2007 were retrospectively reviewed in Germany. They had all been identified at or reported to the Reference Laboratory for Pseudallescheria/Scedosporium spp. in Berlin. Twelve of 13 patients with haematological disorders and/or on immunosuppressive therapy developed a fatal invasive scedosporiosis. Colonization of the respiratory tract was reported for one patient after heart-lung-transplantation, all six patients with cystic fibrosis and one with chronic sinusitis. Molecular studies of the S. prolificans isolates confirmed that parts of the 18S, the Internal Transcribed Spacer (ITS) regions and the D1/D2 domain of the 28S region of rDNA are monomorphic. However, sequencing of parts of the translation elongation factor EF1-alpha (EF-1α) and the chitin synthase (CHS-1) genes revealed the presence of three and two distinct genotypes, respectively. Two informative mutations were found in EF-1α and a single nucleotide exchange in the CHS-1 gene. [ABSTRACT FROM AUTHOR]

The saprophytic moulds Scedosporium prolificans and Scedosporium apiospermum/Pseudallescheria boydii are an increasing cause of invasive fungal infections in immunocompromised hosts. The growing importance and high mortality rates of invasive disease caused by these fungi necessitates the search for newer treatment strategies. However, clinically available antifungal agents have modest to minimal activity against these organisms that has been confirmed by suboptimal responses in the clinic. Due to this limited in vitro activity and poor clinical response, antifungal combinations and high-dose regimens are frequently recommended to treat these refractory infections. However, development of a pharmacodynamic basis for antifungal dosing in scedosporiosis has been hampered by the limitations in the application of traditional microbiological techniques and endpoints for Scedosporium species. Newer quantitative and qualitative assays have demonstrated utility for measuring drug lethality in filamentous fungi, including Scedosporium species, and may aid in the development of new treatment strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

For the last ten years, non-Aspergillus mold species have been increasingly involved in human invasive infections, probably as a consequence of more intense immunosuppression and prolonged patient survival, and of selective pressure since antifungal agents are currently used for prophylaxis or therapy. Scedosporium prolificans, one of these emerging fungi, has been isolated in a broad spectrum of clinical presentations in humans, including respiratory-tract colonization, superficial or locally invasive infections, and disseminated infections in immunocompromised patients. Here, we report the recent emergence of invasive infections due to S. prolificans in France, and describe four new cases diagnosed during the last six years. Only one disseminated scedosporiosis has been reported before this in France, in 1994. Three out of our four cases were breakthrough infections in immunocompromised patients receiving posaconazole or voriconazole therapy. The aims of the present review were thus to gain a better understanding of scedosporiosis epidemiology and clinical features, and to review recent advances in multimodal management of these infections, including surgery, recovery and/or enhancement of immunity, and antifungal combinations, especially voriconazole plus terbinafine. [ABSTRACT FROM AUTHOR]

Abstract: Isolated from the mycelium of Scedosporium prolificans were complex glycoproteins (RMP-Sp), with three structurally related components (HPSEC). RMP-Sp contained 35% protein and 62% carbohydrate with Rha, Ara, Man, Gal, Glc, and GlcNH2 in a 18:1:24:8:6:5 molar ratio. Methylation analysis showed mainly nonreducing end- of Galp (13%), nonreducing end- (9%), 2-O- (13%), and 3-O-subst. Rhap (7%), nonreducing end- (11%), 2-O- (10%), 3-O- (14%), and 2,6-di-O-subst. Manp units (13%). Mild reductive β-elimination of RMP-Sp gave α-l-Rhap-(1→2)-α-l-Rhap-(1→3)-α-l-Rhap-(1→3)-α-d-Manp-(1→2)-d-Man-ol, with Man-ol substituted at O-6 with β-d-Galp units, a related pentasaccharide lacking β-d-Galp units, and β-d-Galp-(1→6)-[α-d-Manp-(1→2)]-d-Man-ol in a 16:3:1w/w ratio. Traces of Man-ol and Rha-ol were detected. ESI-MS showed HexHex-ol and Hex3–6Hex-ol components. Three rhamnosyl units were peeled off successively from the penta- and hexasaccharide by ESI-MS-MS. The carbohydrate epitopes of RMP-Sp differ from those of the glycoprotein of Pseudallescheria boydii, a related opportunistic pathogen. [Copyright &y& Elsevier]

Because human infections by Scedosporium prolificans are difficult to treat and show a very poor outcome, new therapeutic strategies are needed. Liposomal amphotericin B (LAMB) (40 mg/kg/day) increased significantly the mean survival time in immunosuppressed mice compared with a control group (22.6 vs. 8.8 days). Amphotericin B deoxycholate (1.5 mg/kg/day) and granulocyte colony-stimulating factor (G-CSF) (300 μg/kg/day) were ineffective. The combination of LAMB (40 mg/kg/day) and G-CSF (150 or 300 μg/kg/day) did not improve the results obtained with LAMB alone. [Copyright &y& Elsevier]

Blastoschizomyces capitatus, Scedosporium prolificans and S. apiospermum are emerging fungal pathogens that may cause disseminated disease in neutropenic patients. They can present as fever resistant to antibiotics and to wide-spectrum antifungal agents, although they may involve almost every organ. The proportion of recovery from blood cultures is high and they are characteristically resistant to most antifungal agents. Prognosis is poor unless patients recover from neutropenia. Voriconazole has good in-vitro activity and is currently the drug of choice for these infections. [ABSTRACT FROM AUTHOR]

Invasive infections by Scedosporium prolificans have increased alarmingly in recent years, mainly in immunosuppressed patients. The epidemiology, pathogenesis and the natural habitat of this pathogen are practically unknown. Isolates of S . prolificans were distinguished from one another by inter-simple-sequence-repeat (ISSR) fingerprinting, a technique based on the high degree of polymorphism of the multisatellite genetic markers used. This technique was found useful for typing 84 isolates of S . prolificans from different countries and sources . The assemblage of S . prolificans isolates tested was extremely diverse, with 35 genotypes present. Several patients were found to have been infected or colonized by more than one strain. Overall, this technique facilitates the epidemiological study of S . prolificans infection. [ABSTRACT FROM AUTHOR]

Summary Scedosporium prolificans infections of normal hosts usually require extensive debridement and sometimes amputation to effect cure, due to the intrinsic resistance of this species to available antifungal agents. Newer agents have not tested favourably. Variable results are obtained with voriconazole, and 100% resistance is described with echinocandins. Itraconazole and terbinafine has offered synergy against various moulds including S. prolificans . In vivo success is reported with the azole/terbinafine combination in S. apiospermum pulmonary infection and Pythium insidiosum periorbital cellulitis. We report a case of orthopaedic infection in a non-immunocompromised host with S. prolificans , in which the combinations of itraconazole/terbinafine and voriconazole/terbinafine showed synergy in vitro , and success was achieved without radical surgery, using voriconazole and terbinafine. [ABSTRACT FROM AUTHOR]

Abstract: Infectious complications are frequent following lung transplantation. Tracheobronchial aspergillosis is the predominant fungal infection in these patients. Infections with Scedosporium apiospermium (Pseudoallescheria boydii) and Scedosporium prolificans (Scedosporium inflatum) have mainly been described in bone marrow transplant recipients and only occasionally in solid organ transplant recipients. We analysed risk factors, the clinical course and outcome of seven lung transplant recipients who developed pulmonary scedosporium infection. Scedosporium apiospermium was documented in bronchoalveolar lavage (BAL) of all seven and Scedosporium prolificans in the BAL of four of these patients. Scedosporium was detected 9–58 months after transplantation. Five of the seven patients had been treated for several months with itraconazole because of previous detection of aspergillus in BAL. All seven patients with scedosporium infection showed airway problems, including early ischemic airway stenosis in one and bronchiolitis obliterans syndrome in the other six patients. Combined treatment with itraconazole and fluconazole was not able to eradicate scedosporium. Four of the seven patients died with advanced bronchiolitis obliterans 3–35 months after the diagnosis of pulmonary scedosporium infection. Three patients are currently alive 3, 6 and 7 years after transplantation, showing persistent scedosporium infection. In conclusion, pulmonary scedosporium infection was seen in lung transplant recipients with structurally abnormal airways and under long-term therapy with itraconazole. Eradication of scedosporium proved difficult, but under combined treatment with itraconazole and fluconazole this opportunistic infection did not disseminate. [ABSTRACT FROM AUTHOR]

We describe a case of proven disseminated infection by Scedosporium prolificans in a profoundly neutropenic patient. The patient presented with a fever unresponsive to broad-spectrum antibiotics, endophthalmitis, respiratory failure and a renal abscess. The organism was isolated from bronchoalveolar lavage fluid and from pus obtained through a sterile puncture. Review of the English-language literature identified 28 additional cases; these occurred exclusively in severely neutropenic patients (predominantly leukaemia) and in transplant recipients. Apart from two or possibly three cases, dissemination was uniformly fatal due to persistent neutropenia and inherited resistance of these pathogens to currently available antifungal drugs. At present, the optimal treatment of S. prolificans infections is unknown, but reversal of the underlying deficient immune status appears of great importance. [ABSTRACT FROM AUTHOR]

Scedosporium prolificans is a ubiquitous filamentous fungi that may cause disseminated diseases in neutropenic patients with hematological malignancies. We report a fatal case of renal transplant recipient who developed both infective endocarditis and meningitis due to S. prolificans during treatment with micafungin and itraconazole for chronic necrotizing aspergillosis. Breakthrough Scedosporium infection should be considered among differential diagnosis of invasive fungal diseases in patients with renal transplant recipients receiving antifungal agents. [ABSTRACT FROM AUTHOR]

Scedosporium apiospermum and S. prolificans are fungi of increasing clinical importance, particularly in persons with underlying diseases. We reviewed the records of 59 patients in Australia from whom Scedosporium spp. were isolated from June 30, 1997, through December 31, 2003. S. apiospermum was isolated predominantly from the respiratory tracts of 28 of 31 patients with underlying lung diseases and resulted in 2 infections and 1 death. The annual number of S. apiospermum isolates remained constant. S. prolificans was isolated from 28 patients only after November 1999. Eight patients with acute myeloid leukemia or hematopoietic stem cell transplants had invasive infection; 4 had fungemia and 6 died from infection. S. prolificans caused locally invasive infection in 2 immunocompetent patients and was found in the respiratory tract of 18 patients with underlying respiratory disease but did not cause fungemia or deaths in these patients. Scedosporium spp. showed distinct clinical and epidemiologic features.