Search

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.

We report a very rare case of pulmonary chromomycosis caused by Scedosporium prolificans that developed after lung transplantation and was successfully treated with endobronchial topical amphotericin B instillation. The subject was a woman in her 50s with a history of bilateral lobar lung transplantation from living donors for idiopathic pulmonary hypertension. Eight years after the lung transplantation, chest radiography X-ray and computed tomography showed an abnormal shadow in the right lung. Bronchoscopic findings showed obstruction by a fungal component at the laterobasal bronchus B9. She was diagnosed with pulmonary chromomycosis after S. prolificans was detected in the bronchial aspirate. Systemic antifungal treatment with itraconazole was ineffective. Therefore, we administered topical amphotericin B weekly via endobronchial instillation and replaced oral itraconazole with voriconazole. The endobronchial procedure was safe and tolerable. Bronchial obstruction improved after three 3 instillations. We continued topical amphotericin B instillation once every 3 months for 2 years, and the abnormal shadow nearly disappeared. This case report describes infection by S. prolificans, which rarely becomes an etiologic agent in lung transplant patients, and shows that endobronchial topical amphotericin B instillation is a therapeutic option when systemic antifungal treatment is ineffective.

To describe the non-exenteration management of sino-orbital fungal infection, a life-threatening condition for which orbital exenteration is generally considered a first-line treatment. A retrospective case series is presented of 7 orbits in 6 consecutive patients admitted and treated at 2 major metropolitan tertiary teaching hospitals in Sydney, New South Wales, Australia. Seven orbits in 6 consecutive patients with sino-orbital fungal infection were treated conservatively with surgical debridement and intravenous antifungal agents. Four patients were immunosuppressed and the other 2 patients were otherwise healthy. All presented with pain, proptosis, or loss of vision. Causative organisms found were Mucormycoses, Aspergillus, and Scedosporium prolificans. Exenteration was avoided in all patients as part of their planned management and 5 patients, including 1 with bilateral disease, survived their disease without exenteration. Medical treatment included intravenous liposomal amphotericin B or voriconazole. A single immunosuppressed patient deteriorated and as a last resort, exenteration was performed, but this made no difference to his clinical course and in retrospect could have been avoided as he died of multiple cerebral metastases diagnosed shortly after his deterioration. The authors recommend that patients with sino-orbital fungal disease preferably be treated conservatively, without orbital exenteration.

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.

An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Grasbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog.

Scedosporium prolificans, also known asScedosporium inflatum, is a fungus widespread in soil, sewage, and manure. This species is highly virulent and is an emerging opportunistic pathogen found in penetrating injuries in immunocompromised patients. Here we report on an immunocompetent patient with bilateral hipS. prolificans-associated osteomyelitis and septic arthritis caused by intentional penetrating trauma. The condition was refractory to initial antimicrobial suppression and surgical irrigation and debridement. Successful outcome was achieved after incorporating a bilateral two-stage total-hip-arthroplasty with Voriconazole-loaded cement and spacer.

Scedosporium prolificans is a fungus that has demonstrated resistance against most currently available antifungal agents and which causes a rapidly disseminating and potentially fatal infection. A 68-year-old woman presented with a fever and consolidation in the lung field. Her symptoms and inflammatory reaction did not improve despite treatment with tazobactam/piperacillin, meropenem, and micafungin. Scedosporium prolificans was detected from the patient's bronchial lavage fluid, and we initiated treatment with voriconazole. Voriconazole was effective in shrinking the consolidation and suppressing the inflammatory reaction. The residual lesion was surgically resected because of the risk of systemic dissemination. The patient is currently alive without relapse or dissemination.

International audience

Fungal infections of the spine are rare and most often infect susceptible individuals. Most common infective agents are Candida, Aspergillus, Cryptococcus, Coccidioides and Histoplasma. Infection reaches the spine through haematogenous route and direct spread from an adjacent infected organ or during surgical procedures. It leads to vertebral osteomyelitis, intervertebral disc infection resulting in reduced disc height, endplate erosions and epidural and paravertebral soft tissue masses. Imaging findings are non-specific but useful for discriminating infections from degenerative disease changes and neoplastic conditions. Imaging findings of various common fungal infections affecting the spine are reviewed along with some unusual and rare agents like Scedosporium prolificans. In addition, postoperative fungal infections and infection associated with contaminated prednisolone injection are also briefly reviewed.

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.

Scedosporium infections have become one of the most common cause of deep mold infections. It has also become a potentially dangerous causative agent of local and invasive infections in immunocompromised and occasionally in immunocompetent patients. It exhibits intrinsic resistance to many antifungals making the treatment difficult, thereby increasing the mortality. We present a case of an immunocompetent patient who came with a swelling on the left upper eyelid with a discharging sinus. A diagnosis of frontal lobe abscess was made and the mucopurulent discharge from the sinus was sent to the microbiology laboratory to know the etiology. The KOH wet mount of this discharge showed the presence of septate hyphal elements and the fungal culture yielded the growth of Scedosporium prolificans.The patient was treated with intravenous voriconazole to which he showed a favourable response.

Scedosporium prolificans, a hyaline filamentous fungus, is widely distributed in the environment and is currently an emerging human pathogen, especially among immunocompromised patients. However, S. prolificans endocarditis is rare. We herein report a case of S. prolificans endocarditis in a 64-year-old patient with breast cancer in complete remission for 30 years after chemotherapy and radiation treatment who was not cured. Susceptibility testing showed resistance to all antifungal drugs, except echinocandin. A review of the literature revealed 10 cases of S. prolificans endocarditis; of these, only one involved an immunocompetent host with no risk factors and only two patients survived. In order to improve the mortality rate, it is necessary to establish rapid diagnostic methods and efficient therapeutic approaches.

Background Fungal infection is a significant source of morbidity and mortality in lung-transplant recipients (LTR). To avoid systemic toxicity, various nebulised antifungal agents are used after transplant to prevent or treat invasive fungal infections (IFI). Nebulised liposomal amphotericin B (n-LAB) has been widely used. However, some fungal agents, such as Scedosporium spp. with reduced amphotericin susceptibility, are emerging. Thus, new antifungal drugs are required. Purpose To evaluate prescription profile, efficacy and tolerability of nebulised voriconazole (n-V) administered at a dose of 40 mg twice-daily in LTR in a tertiary hospital. Material and methods Observational, retrospective study of patients who underwent lung transplant (LT) between January 2008 and September 2017 who received n-V. Data collected from electronic health records were age at LT, cause of transplantation, post-transplant fungal isolations in bronchoalveolar lavage, bronchial suction or sputum, n-LAB use, n-V treatment duration, and adverse effects and efficacy in terms of fungal infection resolution or culture negativity. Results Eleven LTR received n-V, average age 40 (20–66). Causes of transplantation were: six diffuse parenchymal lung disease (DPLD), four cystic fibrosis (CF) and one chronic obstructive pulmonary disease (COPD). Ten patients (91%) previously received n-LAB as antifungal prophylaxis in the post-transplant period. Fungal isolations observed in LTR who received n-V were: Aspergillus Terreus (two), Aspergillus Fumigatus (two), Paecilomyces Lilacinus (three), Scedosporium Apisopermum (three), Scedosporium Prolificans (one) and Scedosporium Aurantiacum (one). There were five cases (46%) of fungal pulmonary infection, three (27%) of airway colonisation, two (18%) IFI and one (9%) S. Apiospermum mycetoma. Average treatment duration was 9.5 months (SD: 6) and no adverse effects were reported. Culture negativity took place in 82% of cases and there was one exitus related to S. Apiospermum and S. Prolificans IFI with n-V therapy duration of 9 months. Conclusion Nebulised voriconazole seems to be an effective alternative to prevent and treat fungal infections when n-LAB antifungal spectrum is not adequate to airway isolations. That occurs in most Scedosporium spp., Paecilomyces spp. and some Aspergillus spp. Its tolerability is good, although n-V is not commercially available and it is prepared from intravenous vials. Further studies will be required to accurately assess the use of n-V in clinical practice. No conflict of interest

Eculizumab has become the standard of care for patients with paroxysmal nocturnal hemoglobinuria (PNH). As more patients are treated, the long-term outcomes of these patients will become apparent. We recently treated a patient who developed PNH in the setting of aplastic anemia. The patient developed acute myeloid leukemia less than three years after initiating eculizumab. The patient also died suddenly from Scedosporium sepsis during induction therapy. This patient's course seemed more aggressive than would be expected. The possible effect of complement blockade is discussed.

Infections due to Scedosporium/Pseudallescheria species are increasingly recognized in both immunocompromised and immunocompetent hosts. Patients with organ and stem cell transplants and malignancy are at high risk for infection. Infection is also acquired through trauma and near-drowning incidents. Scedosporium apiospermum complex and Lomentospora prolificans (previously Scedosporium prolificans) account for most infections. Increasing use of sequencing-based molecular tools to identify these fungi has enabled better understanding of species-specific differences in geographical distribution, clinical epidemiology and presentation. S. apiospermum complex infections occur worldwide, affect diverse host groups and has protean clinical manifestations. L. prolificans typically causes infection in immunocompromised patients and is associated with disseminated infection and high mortality. S. aurantiacum (a member of S. apiospermum complex) has a propensity to be isolated from patients with cystic fibrosis and other chronic lung disease. Case clusters of L. prolificans infection have occurred. Appreciation of epidemiology is important to inform rapid diagnostics and antifungal therapy.

Here we describe the sequencing and assembly of the pathogenic fungusLomentospora prolificansusing a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. The resulting assembly is highly contiguous, containing a total of 37,630,066 bp with over 98% of the sequence in just 26 scaffolds. Annotation identified 8,656 protein-coding genes. Pulsed-field gel analysis suggests that this organism contains at least 7 and possibly 11 chromosomes, the two longest of which have sizes corresponding closely to the sizes of the longest scaffolds, at 6.6 and 5.7 Mb.

The filamentous fungus Lomentospora (Scedosporium) prolificans is an emerging opportunistic pathogen associated with fatal infections in patients with disturbed immune function. Unfortunately, conventional therapies are hardly of any use against this fungus due to its intrinsic resistance. Therefore, we performed an integrated study of the L. prolificans responses to the first option to treat these mycoses, namely voriconazole, with the aim of unveiling mechanisms involved in the resistance to this compound. To do that, we used a wide range of techniques, including fluorescence and electron microscopy to study morphological alterations, ion chromatography to measure changes in cell-wall carbohydrate composition, and proteomics-based techniques to identify the proteins differentially expressed under the presence of the drug. Significantly, we showed drastic changes occurring in cell shape after voriconazole exposure, L. prolificans hyphae being shorter and wider than under control conditions. Interestingly, we proved that the architecture and carbohydrate composition of the cell wall had been modified in the presence of the drug. Specifically, L. prolificans constructed a more complex organelle with a higher presence of glucans and mannans. In addition to this, we identified several differentially expressed proteins, including Srp1 and heat shock protein 70 (Hsp70), as the most overexpressed under voriconazole-induced stress conditions. The mechanisms described in this study, which may be directly related to L. prolificans antifungal resistance or tolerance, could be used as targets to improve existing therapies or to develop new ones in order to successfully eliminate these mycoses. This work has been supported by grants (GIU15/36 and UFI11/25) from the UPV/EHU. AP was supported by a predoctoral fellowship from the UPV/EHU, and IB and AA were supported by predoctoral fellowships from the Basque Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Scedosporium prolificans is a rare cause of fungal sclerokeratitis following pterygium excision with beta-irradiation or Mitomycin C (MMC). We present a case of a male horticulturist with history of bilateral pterygium excision with MMC who presented for evaluation of refractory sclerokeratitis and was found to have S. prolificans sclerokeratitis. Despite aggressive topical and combination intravenous antifungal therapy, enucleation of the affected eye was required due to evidence of posterior scleral extension on imaging. S. prolificans should be considered in cases of refractory sclerokeratitis. Infections due to S. prolificans often do not respond to antifungal therapies alone and often require swift surgical management.

Disseminated scedosporiosis is rare in dogs and is usually reported in German Shepherds with suspected heritable immunodeficiency. This is the first report of disseminated scedosporiosis due to Scedosporium prolificans in a Labrador retriever dog that was receiving immunosuppressive drug therapy for treatment of immune-mediated haemolytic anaemia. Despite cessation of immunosuppressive medications and an initial response to aggressive treatment with voriconazole and terbinafine the dog developed progressive disease with neurological signs necessitating euthanasia six months from diagnosis., Highlights • Disseminated scedosporiosis due to Scedosporium prolificans is described in a dog. • Chronic prednisolone and cyclosporine therapy preceded disseminated scedosporiosis. • Combination therapy with oral voriconazole and terbinafine was prescribed. • Despite an initial response progressive disease occurred.

Introduction Infection remains the primary cause of morbidity and mortality in the burns patient population. While candidal infection in burns patients is well described, there is dearth of information regarding non-candidal fungal infections in this setting. Method All adult burns patients who developed non-candidal fungal infections over a period of 10 years (between January 2001 and June 2011) were included. Retrospective data analyzed included patient demographics, organisms cultured, antibiotic susceptibility patterns, treatment, length of stay and overall mortality. Results The incidence of non-candidal fungal infections at our centre over the time period studied was 0.04%. A total of 12 patients had a fungus other than Candida isolated. Of these 12 patients, seven were thought to have clinically significant fungal infections and were treated with targeted anti-fungal therapy. Between them, seven species of fungus were isolated: Aspergillus fumigatus ( n =7), Scedosporium prolificans ( n =2), Fusarium solani ( n =2), Mucor spp. ( n =2), Absydia corymbifera ( n =1), Penicillium ( n =1) and Alternaria spp. ( n =1). Of those definitively treated, two died, although fungal infection was not believed to be a contributing factor to these deaths. Conclusion We demonstrate a low incidence and attributable mortality of non-candidal fungal infections in the setting of early antifungal therapy and extensive surgical debridement at our state-wide Burns Service.

International audience; As a result of fundamental changes in the International Code of Nomenclature on the use of separate names for sexual and asexual stages of fungi, generic names of many groups should be reconsidered. Members of the ECMM/ISHAM working group on Pseudallescheria/Scedosporium infections herein advocate a novel nomenclature for genera and species in Pseudallescheria, Scedosporium and allied taxa. The generic names Parascedosporium, Lomentospora, Petriella, Petriellopsis, and Scedosporium are proposed for a lineage within Microascaceae with mostly Scedosporium anamorphs producing slimy, annellidic conidia. Considering that Scedosporium has priority over Pseudallescheria and that Scedosporium prolificans is phylogenetically distinct from the other Scedosporium species, some name changes are proposed. Pseudallescheria minutispora and Petriellidium desertorum are renamed as Scedosporium minutisporum and S. desertorum, respectively. Scedosporium prolificans is renamed as Lomentospora prolificans.

Scedosporium prolificans is a pathogenic mold resistant to current antifungals, and infection results in high mortality. Simultaneous targeting of both ergosterol biosynthesis and heat shock protein 90 (Hsp90) or the cal- cineurin pathway in S. prolificans may be an important strategy for enhancing the potency of antifungal agents. We hypothesized that the inactive triazoles posaconazole (PCZ) and itraconazole (ICZ) acquire fungicidal activity when combined with the calcineurin inhibitor tacrolimus (TCR) or Hsp90 inhibitor 17-demethoxy-17-(2-propenylamino) geldanamycin (17AAG). PCZ, ICZ, TCR and 17AAG alone were inactive in vitro against S. prolificans spores (MICs > 128 μg/ml). In contrast, MICs for PCZ or ICZ in combination with TCR or 17AAG (0.125-0.50 μg/ml) were much lower compared with drug alone. In addition PCZ and ICZ in combination with TCR or 17AAG became fungicidal. Because apoptosis is regulated by the calcineurin pathway in fungi and is un- der the control of Hsp90, we hypothesized that this synergistic fungicidal ef- fect is mediated via apoptosis. This observed fungicidal activity was mediated by increased apoptosis of S. prolificans germlings, as evidenced by reactive oxygen species accumulation, decreased mitochondrial membrane potential, phosphatidylserine externalization, and DNA fragmentation. Furthermore, induction of caspase-like activity was correlated with TCR or 17AAG + PCZ/ICZ-induced cell death. In conclusion, we report for the first time that PCZ or ICZ in combination with TCR or 17AAG renders S. prolificans exquisitely sensitive to PCZ or ICZ via apoptosis. This finding may stimulate the develop- ment of new therapeutic strategies for patients infected with this recalcitrant fungus.

This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/1462-2920.12470

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.

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.

To determine if there has been an increase in Scedosporium infection at our cancer center, we compared the incidence to previously published data from our institution. A retrospective analysis of records of 12 patients with cancer with culture-proven Scedosporium infection from the last decade was performed. Types of malignancy included both hematologic disease, such as leukemia and lymphoma, and solid tumors, such as breast and lung cancer. Risk factors for Scedosporium infection include prolonged neutropenia, bronchiectasis, and immunosuppressive therapy. The mortality rate for patients with Scedosporium prolificans infection was 75%, whereas patients with Scedosporium apiospermum infection were more likely to die of their underlying malignancy than infection.

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.

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.

Many victims of the tsunami that occurred following the Great East Japan Earthquake on March 11, 2011 developed systemic disorders owing to aspiration pneumonia. Herein, we report a case of tsunami lung wherein Scedosporium aurantiacum was detected in the respiratory tract. A magnetic resonance image of the patient's head confirmed multiple brain abscesses and lateral right ventricle enlargement. In this case report, we describe a potential refractory multidrug-resistant infection following a tsunami disaster.

Scedosporium prolificans have been reported to be resistant to all antifungals including the newer azoles and echinocandins. We report an unusual case of repeated S. prolificans infection of the heart valves in an immunocompetent patient.

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.

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.

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.

In this study, we analyzed the impact of immunization with the peptidorhamnomannan (PRM) from the cell wall of the fungus Scedosporium (Lomentospora) prolificans in a murine model of invasive scedosporiosis. Immunization with PRM decreased the survival of mice infected with S. prolificans. Immunization of mice with PRM led to decreased secretion of pro-inflammatory cytokines and chemokines but did not affect the secretion of IL-10. Mice immunized with PRM showed an increase in IgG1 secretion, which is an immunoglobulin linked to a nonprotective response. Splenocytes isolated from mice infected with S. prolificans and immunized with PRM showed no differences in the percentages of Th17 cells and no increase in the frequency of the CD4(+)CD62L(Low) T cell population. PRM-immunized mice showed a significant increase in the percentage of Treg cells. In summary, our results indicated that immunization with PRM did not assist or improve the immunological response against S. prolificans infection. PRM exacerbated the infection process by reducing the inflammatory response, thereby facilitating colonization, virulence and dissemination by the fungus.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1372-y) contains supplementary material, which is available to authorized users.

Disseminated Scedosporium prolificans infection in a 1-year-old female spayed German Shepherd dog is described. Clinical signs were predominantly associated with fungal pyelonephritis and the organism was cultured from the urine. The dog was treated with itraconazole and later, terbinafine was added. Subsequent antifungal susceptibility testing of the isolate showed it to be resistant to all available antifungal drugs. The dog was euthanased because of acute abdominal haemorrhage and associated clinical deterioration. Postmortem examination revealed extensive pyogranulomas containing fungal organisms in the renal parenchyma, myocardium, bone marrow, skeletal muscle, liver, lung, spleen, multiple lymph nodes and pancreas.

Fusarium ( n = 67) and Scedosporium ( n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum , 7 Scedosporium aurantiacum , and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC 90 values (μg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 μg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC 90 was 0.12 μg/ml for S. apiospermum , but 1 to >8 μg/ml for other tested agents. Against S. aurantiacum , the MEC 50 for E1210 was 0.06 μg/ml versus 0.5 to >8 μg/ml for the comparators. Against S. prolificans , the MEC 90 for E1210 was only 0.12 μg/ml, compared to >4 μg/ml for amphotericin B and >8 μg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; ±2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B-resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results.

Answer: Scedosporium prolificans . Scedosporium prolificans is a filamentous fungus that was discovered in greenhouse soil in 1974 ([1][1]). Scedosporium species are ubiquitous saprophytic fungi found in soil and polluted water. Infection is acquired following traumatic implantation or aspiration of

Two months following the surgical repair of an acute, open, comminuted, and articular fracture of the left olecranon, a 15-year-old American Saddlebred gelding presented with nonweight-bearing lameness. A fungus cultured from the cubital joint was identified as Scedosporium prolificans by sequencing of the D2 large subunit ribosomal DNA region and subsequently confirmed by phenotypic methods. Therapy with systemic fluconazole, terbinafine and intra-articular voriconazole was attempted, but was unsuccessful.

Dapsone (4,40diaminodiphenyl sulphone) has been used since the middle of the 20th century for leprosy treatment, usually in combination with rifampin and clofazimine. Dapsone hypersensitivity syndrome (DHS) occurs in 0.5-3% of patients treated with this drug. The exact immune mechanism behind this idiosyncratic reaction with multi-organ involvement is unclear. Some genetic and environmental factors, by increasing the production of dapsone-reactive metabolites or affecting the ability of the liver to detoxificate them, may increase the risk of developing DHS. Latency before the onset of symptoms can vary from 2-6 h, in previously sensitised patients, to 6 months [1]. Typical DHS manifestations include high fever, skin rash, malaise, methemoglobinaemia, liver toxicity (jaundice, hepatitis and hepatomegaly) and generalised lymphadenopathy. Acute renal failure, hypersensitivity pneumonia, cholangitis, sensory peripheral neuropathy, pancreatitis and pleural effusion have been reported less frequently [2]. The discontinuation of dapsone and the early initiation of high-dosage systemic corticosteroid therapy are crucial to decrease mortality and morbidity. Scedosporium spp. are hyaline filamentous fungi ubiquitously present in soil, sewage and polluted waters. Although these fungi have a uniform worldwide distribution, they are more commonly found in temperate climates than in tropical climates. The most common species responsible for human disease are Scedosporium apiospermum (teleomorph: Pseudallescheria boydii) and Scedosporium prolificans, both of which are very similar to Aspergillus spp. These pathogens, once mainly known as agents of cutaneous and subcutaneous tissue infections (e.g. maduromycosis) in immunocompetent patients, have recently been reported to cause systemic life-threatening infections in immunocompromised hosts with increasing frequency. Scedosporium-related pneumonia, meningoencephalitis, brain abscesses and endocarditis have been documented in patients with advanced human immunodeficiency virus (HIV) infection and haematological malignancies, as well as in stem cell transplantation recipients. In the international medical literature, there are only a few reports of life-threatening Scedosporium spp. infections in immunocompetent patients. Rodriguez-Tudela et al. [3], in a recent review of 162 cases of scedosporiosis, reported 34 infections in patients with no underlying chronic condition; of note, 23 of these cases (82%) had suffered surgery or traumatism before the acquisition of the infection. Katragkou et al. [4] reviewed 23 cases of Scedosporium apiospermum infection after near-drowning. In this particular condition, Scedosporium apiospermum has been reported to cause severe invasive infections, with frequent central nervous system dissemination, in young and immunocompetent hosts. We report the case of a patient who died of a rapidly progressive pneumonia caused by Scedosporium apiospermum. The patient we describe did not present any typical risk factor for this opportunistic infection, except for a 10-day course of steroid therapy administered to control a DHS. A 53-year-old Indian man presented with a 10-day history of fever, generalised itchy maculopapular rash involving the palms and soles, and jaundice. His past medical history was unremarkable, and he denied taking any medication on a regular basis. He had been living in Italy for the past 26 years, but he had travelled to his L. Ceccarelli G. Calisti (&) D. Delle Rose A. Ricciardi G. Maffongelli P. Sordillo L. Sarmati M. Andreoni Infectious Diseases Unit, Tor Vergata University Hospital, Viale Oxford 81, 00133 Rome, Italy e-mail: giorgiocalisti@gmail.com

Invasive fungal infections (IFI) remain a serious threat to immunocompromised hosts. Current diagnostic methods, including fungal culture and antigen detection, are slow and often lack specificity. Rapid diagnostic tools with increased sensitivity and specificity could improve the care of patients with IFI. Recently, Luminex Molecular Diagnostics (Toronto, Canada) developed 23 analyte-specific reagents (ASRs) for the detection of the most common clinically relevant fungi. This study's objective was to evaluate the sensitivity and specificity of a subset of these ASRs for fungal isolates and clinical specimens. Previously characterized fungal and bacterial isolates ( n = 110), blood culture specimens ( n = 34), and respiratory specimens ( n = 44) were tested using either a Candida 7-plex panel ( Candida albicans , Candida glabrata , Candida tropicalis , Candida parapsilosis , Candida lusitaniae , Candida guilliermondii , and Candida krusei ) or a mold 11-plex panel ( Aspergillus fumigatus , Aspergillus flavus , Aspergillus niger , Aspergillus terreus , Scedosporium prolificans , Scedosporium apiospermum , Fusarium oxysporum / Fusarium solani , Rhizopus arrhizus , Rhizopus microsporus , Mucor indicus , and Cunninghamella bertholletiae ). The Candida 7-plex panel correctly identified all Candida isolates as confirmed by fungal culture and biochemical tests, for a sensitivity and specificity of 100%. The mold 11-plex panel correctly identified all mold isolates tested except for A. niger. Fungal isolates of Rhizopus and Mucor species were not detected, either, although they could represent species other than those targeted by the ASRs. Further evaluation will be necessary to confirm the sensitivities of some of the mold ASRs. Implementation of these ASRs will allow same-day detection of fungal DNA in clinical specimens.

The potential of mMass software search tool with new compound libraries was demonstrated on metabolomics of Scedosporium prolificans, S. apiospermum and Pseudallescheria boydii sensu stricto. Cyclic peptides pseudacyclins, small molecular weight tyroscherin analogues and various lipids were annotated by public software tool (http://www.mmass.org) utilising accurate matrix-assisted laser desorption/ionisation mass spectral data of intact fungal spores. Electrospray ionisation combined with tandem mass spectrometry was used for monohexosylceramide characterisation in fungal extracts.

Since the latest taxonomical changes in the genus Scedosporium by Gilgado et al. in 2010, no species-specific studies on epidemiology and antifungal susceptibility patterns (AFSP) have so far been published. This study aimed to provide qualitative epidemiological data of Scedosporium spp. isolated from cystic fibrosis (CF) patients and immunocompromised patients from Northern Spain. Isolates were identified by using amplified fragment length polymorphism (AFLP), and species-specific AFSP were generated for all currently available antifungal compounds. AFLP was a useful tool for identification to species-level and for the discrimination of inter- and intra-patient isolates. Scedosporium prolificans represents the most prevalent species in the respiratory tract of CF patients and immunocompromised patients in Northern-Spain, followed by Pseudallescheria boydii, P. apiosperma, and P. ellipsoidea. CF patients were exclusively colonised with either P. boydii or S. prolificans. Patients were colonised over years exclusively with isolates affiliated to one species, but some patients were colonised with multiple strains with different AFSP. The sum of those co-colonising strains in one patient, may appear in vitro and in vivo as a multi-resistant S. prolificans isolate, as strains are morphologically identical and might therefore be regarded as only one strain. A majority of Scedosporium strains (with exception of S. prolificans) were found susceptible for voriconazole and micafungin.

The PCR-RLB (reverse line blot hybridisation) was applied as a molecular technique for the detection of members of Pseudallescheria and Scedosporium from sputum of patients with cystic fibrosis (CF). Fifty-nine sputum samples were collected from 52 CF patients, which were analysed by culture and PCR-RLB. Conventional and semi-selective culture yielded five positive samples, but the PCR-RLB hybridisation assay permitted the detection of members of Pseudallescheria/Scedosporium in 32 out of 52 patients (61.5%). In total, PCR-RLB yielded 47 positives. Pseudallescheria apiosperma was detected in 20 samples, while Pseudallescheria boydii and Pseudallescheria aurantiacum were detected in 17 and eight samples, respectively. Six samples gave a positive reaction with two distinct species-specific probes and one sample with three probes. In conclusion, the PCR-RLB assay described in this study allows the detection of Scedosporium spp. in CF sputum samples and the identification of Pseudallescheria apiosperma, P. boydii, S. aurantiacum, Scedosporium prolificans and Pseudallescheria minutispora.

Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two “hot spot” regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1 Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new “hot spot 3” in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES.

Resumen Antecedentes: Scedosporium es un genero que incluye a las especies Scedosporium prolificans y Scedosporium apiospermum. S. apiospermum es la causa de aproximadamente el 25% de las infecciones por hongos filamento-sos diferentes de Aspergillus en pacientes trasplantados de organo solido. Este moho coloniza facilmente lesio-nes residuales y senos faciales, y se encuentran en riesgo especial los pacientes con fibrosis quistica colonizados antes del trasplante y los trasplantados unipulmonares. S. apiospermum es un hongo emergente cuya peculiari-dad es su resistencia inherente a la anfotericina B. Este hecho, unido a la dificultad para realizar su identificacion (respecto a otros mohos sensibles a este antifungico) hace complicado el manejo precoz de las escedosporiasis. Caso clinico: Se presenta un caso de infeccion diseminada por S. apiospermum en un varon de 56 anos con trasplante pulmonar. Un micetoma en la pierna derecha fue el primer hallazgo de la enfermedad diseminada. En la discusion se hace referencia a la experiencia publicada y las pautas de tratamiento actual. El trata-miento debe ser energico y de tipo medico-quirurgico cuando el abordaje sea posible. Conclusiones: Una conclusion a extraer de este caso clinico es que se debe recapacitar sobre el posible desa-rrollo de infecciones por hongos emergentes durante el empleo de profilaxis antifungica. Como conclusion final hay que resaltar que la colonizacion por Scedosporium en pacientes trasplantados de pulmon con le-siones anatomicas locales y con inmunosupresion alta se deberia manejar con un tratamiento antifungico agresivo, sobre todo en un receptor de un unico pulmon o si el paciente tiene rechazo cronico. © 2011 Revista Iberoamericana de Micologia. Publicado por Elsevier Espana, S.L. Todos los derechos reservados.

Scedosporium spp. are dematiaceous molds increasingly reported as opportunistic pathogens, particularly in immunocompromised patients with hematological malignancies such as those with acute leukem...