RARE DISEASE
Scedosporiosis
Scedosporiosis
Scedosporiosis
Drug discovery
4
drugs
With orphan designations
Overview
Scedosporiosis is a life-threatening fungal infection caused by Scedosporium spp. (including S. apiospermum, S. prolificans, and S. aurantiacum), which primarily affect immunocompromised hosts. These fungi are environmental molds associated with high mortality (42–90%), particularly in disseminated or CNS infections. Risk factors include hematologic malignancies, transplants, cystic fibrosis, and near-drowning events. Diagnosis is challenging due to intrinsic antifungal resistance, with voriconazole as first-line therapy, though outcomes remain poor in refractory cases.
Population
– Immunocompromised individuals (hematologic malignancies, HSCT/SOT recipients) [7][16].
– Patients with chronic lung disease (e.g., cystic fibrosis) or trauma/near-drowning exposure [1][6].
– Higher incidence in males (63%) and regions with S. prolificans prevalence (e.g., Australia, Spain) [2][6].
Burden
– Mortality: 42–46% overall; 77% in acute leukemia, rising to 100% in S. prolificans fungemia [7][12][16].
– High healthcare costs due to prolonged antifungal regimens, ICU stays, and surgical interventions [19].
– Disseminated disease occurs in >75% of immunocompromised patients, often with CNS involvement [12][16].
Therapies
Categories: rare infectious diseases
Research Papers
165 drug discovery papers about Scedosporiosis, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
165 drug discovery papers about Scedosporiosis, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-23 | Fosmanogepix: A comprehensive review of its origin, mechanism, antifungal efficacy, and resistance (Review)
The escalating burden of invasive fungal infections, compounded by rising antifungal resistance and evolving pathogen epidemiology, underscores the urgent need for novel agents.There is a requirement for these novel agents to combine broad-spectrum activity with >90% oral bioavailability and a 48% acceptable safety profile.Fosmanogepix, an N-phosphonooxymethylene prodrug of manogepix (APX001A), is a first-in-class glycosylphosphatidylinositol (GPI)-anchored wall transfer protein 1 (Gwt1) inhibitor in Phase III clinical trials for invasive fungal infections.It is a potent inhibitor of the fungal enzyme Gwt1, which blocks GPI-anchored protein maturation and disrupts cell wall integrity.Manogepix has broad in vitro activity against yeasts and molds, including drug-resistant and intrinsically resistant pathogens.Fosmanogepix shows notable in vivo efficacy in mouse and rabbit models of disseminated candidiasis, coccidioidomycosis, fusariosis, pulmonary aspergillosis, scedosporiosis and mucormycosis.Clinical trials have demonstrated high oral bioavailability (90%), allowing seamless intravenous-to-oral switching.Favorable drug-drug interaction, tolerability and effective tissue distribution profiles make fosmanogepix an attractive option for treating invasive fungal infections.However, emerging resistance mechanisms, including Gwt1 target mutations (such as V162A/V163A), efflux pump overexpression mediated by transcription factor mutations (Tac1B, Tac1, Pdr1), and calcineurin-dependent calcium signaling activation, pose potential threats to its long-term clinical utility.The present narrative review summarized published findings on fosmanogepix, encompassing its origin, mechanism of action, antifungal efficacy, resistance mechanisms, and combination strategies through in vitro, in vivo, and clinical investigations.Contents 1. Introduction 2. Literature search and study selection 3. Origin and derivatives of fosmanogepix 4. Antifungal mechanism and resistance mechanisms of fosmanogepix 5. Antifungal efficacy of fosmanogepix 6. Clinical positioning of fosmanogepix 7.
2026-06-04 | New Perspectives on Antimicrobial Agents: Fosmanogepix.
Invasive fungal infections (IFIs) are associated with high mortality rates and pose important therapeutic challenges because of the limited number of antifungal drug classes, their toxicity, and the emergence of resistance. Novel first-in-class antifungal agents have been recently approved (ibrexafungerp) or are currently being tested in clinical trials and are available via expanded access programs (olorofim, fosmanogepix). Among them, fosmanogepix (a prodrug of manogepix) represents a promising future therapeutic option for many IFIs because of its broad-spectrum antifungal activity and its favorable pharmacologic properties, such as oral bioavailability, extended tissue distribution (including the central nervous system), a good safety profile, and the absence of relevant drug-drug interactions. Fosmanogepix may become an interesting alternative option for the treatment of invasive candidiasis due to multidrug-resistant isolates (e.g., Candidozyma auris) or invasive aspergillosis due to azole-resistant Aspergillus spp. It also demonstrated very encouraging results for the treatment of invasive fusariosis and other refractory mold infections (e.g., scedosporiosis, lomentosporiosis). Novel gepix compounds have been developed and could make their niche in the future (e.g., APX2039, prodrug: APX2096, for cryptococcal meningitis, and APX2020, prodrug: APX2097, for coccidioidomycosis). This review discusses the future place of fosmanogepix in the antifungal armamentarium against IFIs.
2026-05-25 | Fatal cerebral scedosporiosis in a liver transplant recipient: Diagnostic pitfalls and antifungal resistance.
Scedosporium boydii causes lethal central nervous system (CNS) disease in transplant recipients and is intrinsically resistant to amphotericin B. A 54-year-old living-donor liver transplant recipient re-admitted (Day 0) with fever and diarrhoea, rapidly deteriorated neurologically, and developed ventriculitis with hydrocephalus. Liquid culture yielded a floating "fungal ball" by Day +8. Microscopy suggested Scedosporium/Lomentospora spp, MALDI-TOF, and ITS sequencing confirmed S. boydii. Amphotericin B MIC was 4.0 μg/mL; voriconazole MIC 0.03 μg/mL. Despite IV voriconazole (with intraventricular caspofungin) and neurosurgery, the patient died of complications. Early molecular identification and prompt switch from amphotericin B to azole-based therapy are critical in post-transplant CNS scedosporiosis.
2026-03-27 | Scedosporium apiospermum: An Emerging yet Overlooked Fungal Pathogen in Veterinary Medicine-A Case-Based Review.
Scedosporium apiospermum is an emerging filamentous fungus of increasing clinical relevance in human and veterinary medicine. Previously regarded as a ubiquitous soil saprophyte, it is now recognized as an opportunistic pathogen causing a wide spectrum of localized and systemic infections, particularly in immunocompromised hosts. Although infections in animals are considered rare, they are likely underdiagnosed or misidentified as aspergillosis or fusariosis due to overlapping clinical features and morphological similarities. The first confirmed animal isolate of S. apiospermum in the Western Balkans, identified in 2024 from the milk of a cow with clinical mastitis, highlights the need for increased awareness and accurate diagnostic approaches for this neglected pathogen in veterinary practice. This review outlines key information on S. apiospermum infections in animals, including routes of infection, predisposing factors, clinical and pathological features, laboratory diagnostic principles, and antifungal susceptibility profiles of animal-derived isolates. Additionally, we present a chronologically organized, tabulated overview of documented cases of scedosporiosis in domestic animals, highlighting the diversity of affected species and the variability in treatment outcomes. This review aims to support early recognition, facilitate differential diagnosis, and contribute to improved management of S. apiospermum infections in veterinary practice.
2026-03-04 | Cutaneous Scedosporium infection mimicking malignancy in a kidney transplant recipient: A case report.
Cutaneous Scedosporium infection represents an extremely rare opportunistic fungal complication in solid-organ transplant recipients, often mimicking post-transplant skin malignancies due to chronic immunosuppression. A 75-year-old woman, kidney transplanted in 2022 for IgA nephropathy on tacrolimus, mycophenolate, and prednisone, developed progressive firm nodular lesions on the left lower limb over two months. Punch biopsy revealed granulomatous inflammation with septate hyphae on Gomori-Grocott stain; culture confirmed Scedosporium spp. CT excluded dissemination. Voriconazole (6 mg/kg loading dose, then 4 mg/kg maintenance dose) combined with surgical debridement, negative-pressure wound therapy, and skin grafting achieved complete healing at three months, with no recurrence at 12 months. Early biopsy is crucial to differentiate this rare entity from squamous cell carcinoma, enabling multidisciplinary success.
proteins
2022-10-21 | Non-Aspergillus mould lung infections.
Non-Aspergillus filamentous fungi causing invasive mould infections have increased over the last years due to the widespread use of anti-Aspergillus prophylaxis and increased complexity and survival of immunosuppressed patients. In the few studies that have reported on invasive mould infection epidemiology, Mucorales are the most frequently isolated group, followed by either Fusarium spp. or Scedosporium spp. The overall incidence is low, but related mortality is exceedingly high. Patients with haematological malignancies and haematopoietic stem cell transplant recipients comprise the classical groups at risk of infection for non-Aspergillus moulds due to profound immunosuppression and the vast use of anti-Aspergillus prophylaxis. Solid organ transplant recipients also face a high risk, especially those receiving lung transplants, due to direct exposure of the graft to mould spores with altered mechanical and immunological elimination, and intense, associated immunosuppression. Diagnosing non-Aspergillus moulds is challenging due to unspecific symptoms and radiological findings, lack of specific biomarkers, and low sensitivity of cultures. However, the advent of molecular techniques may prove helpful. Mucormycosis, fusariosis and scedosporiosis hold some differences regarding clinical paradigmatic presentations and preferred antifungal therapy. Surgery might be an option, especially in mucormycosis. Finally, various promising strategies to restore or enhance the host immune response are under current evaluation.
2022-10-11 | Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases
Abstract Background Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs). Methods The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted. Results Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response). Conclusions Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.
2019-08-28 | Therapeutic Challenges of Non-Aspergillus Invasive Mold Infections in Immunosuppressed Patients.
While Aspergillus spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as Mucorales, Fusarium, and Scedosporium spp. are increasingly encountered in an expanding population of patients with severe and prolonged immunosuppression. High potential for tissue invasion and dissemination, resistance to multiple antifungals and high mortality rates are hallmarks of these non-Aspergillus invasive mold infections (NAIMIs). Assessment of drug efficacy is particularly difficult in the complex treatment scenarios of NAIMIs. Specifically, correlation between in vitro susceptibility and in vivo responses to antifungals is hard to assess, in view of the multiple, frequently interrelated factors influencing outcomes, such as pharmacokinetic/pharmacodynamic parameters determining drug availability at the site of infection, the net state of immune suppression, delay in diagnosis, or surgical debulking of infectious foci. Our current therapeutic approach of NAIMIs should evolve toward a better integration of the dynamic interactions between the pathogen, the drug and the host. Innovative concepts of experimental research may consist in manipulating the host immune system to induce a specific antifungal response or targeted drug delivery. In this review, we discuss the challenges in the management of NAIMIs and provide an update about the latest advances in diagnostic and therapeutic approaches.
2016-06-24 | Peptidorhamnomannan negatively modulates the immune response in a scedosporiosis murine model
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.
2016-03-01 | Scedosporium apiospermum infections and the role of combination antifungal therapy and GM-CSF: A case report and review of the literature
Scedosporium apiospermum, a ubiquitous environmental mold, is increasingly reported as causing invasive fungal disease in immunocompromised hosts. It poses a therapeutic challenge due to its intrinsic resistance to traditional antifungals and ability to recur despite demonstrating susceptibility. We present an immunocompromised patient with a cutaneous S. apiospermum infection that disseminated despite treatment with voriconazole, the drug of choice. Adding echinocandins and GM-CSF provided partial recovery, indicating a potential synergistic role of dual-antifungal and immunotherapeutic agents.
cell therapies
2026-05-22 | Hematopoietic stem cell transplantation following invasive mold infection in chronic granulomatous disease: Insights from a case series and literature review.
Chronic granulomatous disease (CGD) is an inborn error of immunity leading to severe invasive mold infections (IMIs). Questions remain regarding the safety of hematopoietic stem cell transplantation (HSCT) in patients following IMI. We retrospectively collected data from CGD patients undergoing HSCT within 2 years after a diagnosis of probable or proven IMI in France. The primary endpoint was to describe 1-year overall survival (OS). 14 patients were included, with aspergillosis (n = 10), mucormycosis (N = 2), scedosporiosis, or lomentosporiosis (n = 1 each). IMI status at time of HCST included four in complete response, four in partial response (PR), one in stable response (SR), and five with disease progression (DP). 1-year OS was 86 % (12/14). Two patients with scedosporiosis and lomentosporiosis died before engraftment. The remaining patients all achieved engraftment followed by prolonged clinical response of IMI. HSCT appears safe in patients with complete response or PR of IMI and could be a promising curative option for progressive IMI, specifically in those with invasive aspergillosis.
small molecules
2026-09-23 | Fosmanogepix: A comprehensive review of its origin, mechanism, antifungal efficacy, and resistance (Review)
The escalating burden of invasive fungal infections, compounded by rising antifungal resistance and evolving pathogen epidemiology, underscores the urgent need for novel agents.There is a requirement for these novel agents to combine broad-spectrum activity with >90% oral bioavailability and a 48% acceptable safety profile.Fosmanogepix, an N-phosphonooxymethylene prodrug of manogepix (APX001A), is a first-in-class glycosylphosphatidylinositol (GPI)-anchored wall transfer protein 1 (Gwt1) inhibitor in Phase III clinical trials for invasive fungal infections.It is a potent inhibitor of the fungal enzyme Gwt1, which blocks GPI-anchored protein maturation and disrupts cell wall integrity.Manogepix has broad in vitro activity against yeasts and molds, including drug-resistant and intrinsically resistant pathogens.Fosmanogepix shows notable in vivo efficacy in mouse and rabbit models of disseminated candidiasis, coccidioidomycosis, fusariosis, pulmonary aspergillosis, scedosporiosis and mucormycosis.Clinical trials have demonstrated high oral bioavailability (90%), allowing seamless intravenous-to-oral switching.Favorable drug-drug interaction, tolerability and effective tissue distribution profiles make fosmanogepix an attractive option for treating invasive fungal infections.However, emerging resistance mechanisms, including Gwt1 target mutations (such as V162A/V163A), efflux pump overexpression mediated by transcription factor mutations (Tac1B, Tac1, Pdr1), and calcineurin-dependent calcium signaling activation, pose potential threats to its long-term clinical utility.The present narrative review summarized published findings on fosmanogepix, encompassing its origin, mechanism of action, antifungal efficacy, resistance mechanisms, and combination strategies through in vitro, in vivo, and clinical investigations.Contents 1. Introduction 2. Literature search and study selection 3. Origin and derivatives of fosmanogepix 4. Antifungal mechanism and resistance mechanisms of fosmanogepix 5. Antifungal efficacy of fosmanogepix 6. Clinical positioning of fosmanogepix 7.
2026-06-04 | New Perspectives on Antimicrobial Agents: Fosmanogepix.
Invasive fungal infections (IFIs) are associated with high mortality rates and pose important therapeutic challenges because of the limited number of antifungal drug classes, their toxicity, and the emergence of resistance. Novel first-in-class antifungal agents have been recently approved (ibrexafungerp) or are currently being tested in clinical trials and are available via expanded access programs (olorofim, fosmanogepix). Among them, fosmanogepix (a prodrug of manogepix) represents a promising future therapeutic option for many IFIs because of its broad-spectrum antifungal activity and its favorable pharmacologic properties, such as oral bioavailability, extended tissue distribution (including the central nervous system), a good safety profile, and the absence of relevant drug-drug interactions. Fosmanogepix may become an interesting alternative option for the treatment of invasive candidiasis due to multidrug-resistant isolates (e.g., Candidozyma auris) or invasive aspergillosis due to azole-resistant Aspergillus spp. It also demonstrated very encouraging results for the treatment of invasive fusariosis and other refractory mold infections (e.g., scedosporiosis, lomentosporiosis). Novel gepix compounds have been developed and could make their niche in the future (e.g., APX2039, prodrug: APX2096, for cryptococcal meningitis, and APX2020, prodrug: APX2097, for coccidioidomycosis). This review discusses the future place of fosmanogepix in the antifungal armamentarium against IFIs.
2026-05-25 | Fatal cerebral scedosporiosis in a liver transplant recipient: Diagnostic pitfalls and antifungal resistance.
Scedosporium boydii causes lethal central nervous system (CNS) disease in transplant recipients and is intrinsically resistant to amphotericin B. A 54-year-old living-donor liver transplant recipient re-admitted (Day 0) with fever and diarrhoea, rapidly deteriorated neurologically, and developed ventriculitis with hydrocephalus. Liquid culture yielded a floating "fungal ball" by Day +8. Microscopy suggested Scedosporium/Lomentospora spp, MALDI-TOF, and ITS sequencing confirmed S. boydii. Amphotericin B MIC was 4.0 μg/mL; voriconazole MIC 0.03 μg/mL. Despite IV voriconazole (with intraventricular caspofungin) and neurosurgery, the patient died of complications. Early molecular identification and prompt switch from amphotericin B to azole-based therapy are critical in post-transplant CNS scedosporiosis.
2026-03-27 | Scedosporium apiospermum: An Emerging yet Overlooked Fungal Pathogen in Veterinary Medicine-A Case-Based Review.
Scedosporium apiospermum is an emerging filamentous fungus of increasing clinical relevance in human and veterinary medicine. Previously regarded as a ubiquitous soil saprophyte, it is now recognized as an opportunistic pathogen causing a wide spectrum of localized and systemic infections, particularly in immunocompromised hosts. Although infections in animals are considered rare, they are likely underdiagnosed or misidentified as aspergillosis or fusariosis due to overlapping clinical features and morphological similarities. The first confirmed animal isolate of S. apiospermum in the Western Balkans, identified in 2024 from the milk of a cow with clinical mastitis, highlights the need for increased awareness and accurate diagnostic approaches for this neglected pathogen in veterinary practice. This review outlines key information on S. apiospermum infections in animals, including routes of infection, predisposing factors, clinical and pathological features, laboratory diagnostic principles, and antifungal susceptibility profiles of animal-derived isolates. Additionally, we present a chronologically organized, tabulated overview of documented cases of scedosporiosis in domestic animals, highlighting the diversity of affected species and the variability in treatment outcomes. This review aims to support early recognition, facilitate differential diagnosis, and contribute to improved management of S. apiospermum infections in veterinary practice.
2026-03-04 | Cutaneous Scedosporium infection mimicking malignancy in a kidney transplant recipient: A case report.
Cutaneous Scedosporium infection represents an extremely rare opportunistic fungal complication in solid-organ transplant recipients, often mimicking post-transplant skin malignancies due to chronic immunosuppression. A 75-year-old woman, kidney transplanted in 2022 for IgA nephropathy on tacrolimus, mycophenolate, and prednisone, developed progressive firm nodular lesions on the left lower limb over two months. Punch biopsy revealed granulomatous inflammation with septate hyphae on Gomori-Grocott stain; culture confirmed Scedosporium spp. CT excluded dissemination. Voriconazole (6 mg/kg loading dose, then 4 mg/kg maintenance dose) combined with surgical debridement, negative-pressure wound therapy, and skin grafting achieved complete healing at three months, with no recurrence at 12 months. Early biopsy is crucial to differentiate this rare entity from squamous cell carcinoma, enabling multidisciplinary success.
proteins
2022-10-21 | Non-Aspergillus mould lung infections.
Non-Aspergillus filamentous fungi causing invasive mould infections have increased over the last years due to the widespread use of anti-Aspergillus prophylaxis and increased complexity and survival of immunosuppressed patients. In the few studies that have reported on invasive mould infection epidemiology, Mucorales are the most frequently isolated group, followed by either Fusarium spp. or Scedosporium spp. The overall incidence is low, but related mortality is exceedingly high. Patients with haematological malignancies and haematopoietic stem cell transplant recipients comprise the classical groups at risk of infection for non-Aspergillus moulds due to profound immunosuppression and the vast use of anti-Aspergillus prophylaxis. Solid organ transplant recipients also face a high risk, especially those receiving lung transplants, due to direct exposure of the graft to mould spores with altered mechanical and immunological elimination, and intense, associated immunosuppression. Diagnosing non-Aspergillus moulds is challenging due to unspecific symptoms and radiological findings, lack of specific biomarkers, and low sensitivity of cultures. However, the advent of molecular techniques may prove helpful. Mucormycosis, fusariosis and scedosporiosis hold some differences regarding clinical paradigmatic presentations and preferred antifungal therapy. Surgery might be an option, especially in mucormycosis. Finally, various promising strategies to restore or enhance the host immune response are under current evaluation.
2022-10-11 | Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases
Abstract Background Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs). Methods The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted. Results Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response). Conclusions Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.
2019-08-28 | Therapeutic Challenges of Non-Aspergillus Invasive Mold Infections in Immunosuppressed Patients.
While Aspergillus spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as Mucorales, Fusarium, and Scedosporium spp. are increasingly encountered in an expanding population of patients with severe and prolonged immunosuppression. High potential for tissue invasion and dissemination, resistance to multiple antifungals and high mortality rates are hallmarks of these non-Aspergillus invasive mold infections (NAIMIs). Assessment of drug efficacy is particularly difficult in the complex treatment scenarios of NAIMIs. Specifically, correlation between in vitro susceptibility and in vivo responses to antifungals is hard to assess, in view of the multiple, frequently interrelated factors influencing outcomes, such as pharmacokinetic/pharmacodynamic parameters determining drug availability at the site of infection, the net state of immune suppression, delay in diagnosis, or surgical debulking of infectious foci. Our current therapeutic approach of NAIMIs should evolve toward a better integration of the dynamic interactions between the pathogen, the drug and the host. Innovative concepts of experimental research may consist in manipulating the host immune system to induce a specific antifungal response or targeted drug delivery. In this review, we discuss the challenges in the management of NAIMIs and provide an update about the latest advances in diagnostic and therapeutic approaches.
2016-06-24 | Peptidorhamnomannan negatively modulates the immune response in a scedosporiosis murine model
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.
2016-03-01 | Scedosporium apiospermum infections and the role of combination antifungal therapy and GM-CSF: A case report and review of the literature
Scedosporium apiospermum, a ubiquitous environmental mold, is increasingly reported as causing invasive fungal disease in immunocompromised hosts. It poses a therapeutic challenge due to its intrinsic resistance to traditional antifungals and ability to recur despite demonstrating susceptibility. We present an immunocompromised patient with a cutaneous S. apiospermum infection that disseminated despite treatment with voriconazole, the drug of choice. Adding echinocandins and GM-CSF provided partial recovery, indicating a potential synergistic role of dual-antifungal and immunotherapeutic agents.
cell therapies
2026-05-22 | Hematopoietic stem cell transplantation following invasive mold infection in chronic granulomatous disease: Insights from a case series and literature review.
Chronic granulomatous disease (CGD) is an inborn error of immunity leading to severe invasive mold infections (IMIs). Questions remain regarding the safety of hematopoietic stem cell transplantation (HSCT) in patients following IMI. We retrospectively collected data from CGD patients undergoing HSCT within 2 years after a diagnosis of probable or proven IMI in France. The primary endpoint was to describe 1-year overall survival (OS). 14 patients were included, with aspergillosis (n = 10), mucormycosis (N = 2), scedosporiosis, or lomentosporiosis (n = 1 each). IMI status at time of HCST included four in complete response, four in partial response (PR), one in stable response (SR), and five with disease progression (DP). 1-year OS was 86 % (12/14). Two patients with scedosporiosis and lomentosporiosis died before engraftment. The remaining patients all achieved engraftment followed by prolonged clinical response of IMI. HSCT appears safe in patients with complete response or PR of IMI and could be a promising curative option for progressive IMI, specifically in those with invasive aspergillosis.
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Drug Discovery Landscape
4 orphan drug designations for Scedosporiosis.
4 orphan drug designations for Scedosporiosis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Fosmanogepix | small molecules | EMA | — | Basilea Pharmaceutica Deutschland GmbH |
Fosmanogepix | small molecules | EMA | Basilea Pharmaceutica Deutschland GmbH | |
Olorofim | small molecules | FDA | F2G Limited | |
fosmanogepix | small molecules | FDA | Basilea Pharmaceutica Ltd, Allschwil |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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