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Transplant Infectious Disease : An... Apr 2013Despite the adoption of antifungal prophylaxis, fungal infections remain a significant concern in lung transplant recipients. Indeed, some concern exists that such... (Review)
Review
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.
Topics: Aged; Aneurysm, Infected; Antifungal Agents; Aortic Aneurysm; Drug Resistance, Fungal; Female; Humans; Lung Transplantation; Mycoses; Pericarditis; Pyrimidines; Scedosporium; Triazoles; Voriconazole
PubMed: 23387799
DOI: 10.1111/tid.12056 -
Microbiology Spectrum Jun 2023Infections with spp. and Lomentospora prolificans have become a serious threat in clinical settings. The high mortality rates associated with these infections can be...
Infections with spp. and Lomentospora prolificans have become a serious threat in clinical settings. The high mortality rates associated with these infections can be correlated with their multidrug resistance. The development of alternative treatment strategies has become crucial. Here, we investigate the and activity of luliconazole (LLCZ) against Scedosporium apiospermum (including its teleomorph Pseudallescheria boydii) and . The LLCZ MICs were determined for a total of 37 isolates (31 isolates, 6 Scedosporium apiospermum/ strains) according to EUCAST. Furthermore, the LLCZ antifungal activity was tested , using an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] growth kinetics assay and biofilm assays (crystal violet and XTT assay). In addition, a Galleria mellonella infection model was used for treatment assays. The MIC of LLCZ was determined to be 0.25 mg/L for all tested pathogens. Growth was inhibited within 6 to 48 h of the start of incubation. LLCZ inhibited biofilm formation in both preadhesion stages and late-stage adhesion. , a single dose of LLCZ increased the survival rate of the larvae by 40% and 20% for and spp., respectively. This is the first study demonstrating LLCZ activity against and and the first study showing the antibiofilm effect of LLCZ in spp. and S. apiospermum are opportunistic, multidrug-resistant pathogens causing invasive infections in immunosuppressed patients and sometimes in healthy persons. is panresistant against the currently available antifungals, and both species are associated with high mortality rates. Thus, the discovery of novel antifungal drugs exhibiting an effect against these resistant fungi is crucial. Our study shows the effect of luliconazole (LLCZ) against and spp. , as well as in an infection model. These data reveal the previously unknown inhibitory effect of LLCZ against and its antibiofilm effect in spp. It represents an extension of the literature regarding azole-resistant fungi and could potentially lead to the development of future treatment strategies against these opportunistic fungal pathogens.
Topics: Animals; Humans; Scedosporium; Antifungal Agents; Imidazoles
PubMed: 37017567
DOI: 10.1128/spectrum.05130-22 -
International Journal of Infectious... Mar 2020Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups,...
OBJECTIVES
Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections.
METHODS
Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected.
RESULTS
Fifty-five children (median age 9 years [IQR: 5-14]) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment. Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days [IQR: 3-28] versus 61 days [IQR: 16-148]). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 [95% CI 1.35-51.40] and HR 6.12 [95% CI 1.52-24.66], respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 [95% CI 0.11-0.99] and HR 0.09 [95% CI 0.02-0.40], respectively).
CONCLUSIONS
Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome.
Topics: Adolescent; Amphotericin B; Antifungal Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Mycoses; Risk Factors; Scedosporium; Voriconazole
PubMed: 31863876
DOI: 10.1016/j.ijid.2019.12.017 -
Medical Mycology Jun 2009Scedosporium 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... (Review)
Review
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.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Mycoses; Risk Factors; Scedosporium; Treatment Outcome; Young Adult
PubMed: 19031336
DOI: 10.1080/13693780802524506 -
Microbiology Spectrum Feb 2023spp. and are an emerging group of fungi refractory to current antifungal treatments. These species largely affect immunocompromised individuals but can also be lung...
spp. and are an emerging group of fungi refractory to current antifungal treatments. These species largely affect immunocompromised individuals but can also be lung colonizers in cystic fibrosis patients. Although Scedosporium apiospermum is thought to be the predominant species, the group has been expanded to a species complex. The distribution of species within the S. apiospermum species complex and other closely related species in the United States is largely unknown. Here, we used β-tubulin and ITS sequences to identify 37 isolates to the species level. These isolates as well as 13 isolates were tested against a panel of nine antifungal drugs, including the first in novel class orotimide, olorofim. and infections are notoriously hard to treat as these organisms can be resistant to numerous antifungals. The manuscript contributes to our knowledge of the activity of the new antifungal agent olorofim and comparator agents against and against isolates that have been molecularly identified to the species level. The efficacy of olorofim against all species of and was confirmed.
Topics: Humans; Antifungal Agents; Scedosporium; Piperazines; Pyrimidines; Ascomycota; Microbial Sensitivity Tests
PubMed: 36629417
DOI: 10.1128/spectrum.02789-22 -
Journal of AAPOS : the Official... Dec 2013Scedosporium prolificans is an opportunistic fungus with a predilection for sepsis and endophthalmitis in immunocompromised patients. We report a case of endogenous...
Scedosporium prolificans is an opportunistic fungus with a predilection for sepsis and endophthalmitis in immunocompromised patients. We report a case of endogenous S. prolificans endophthalmitis in a 9-year-old girl following chemotherapy for acute myeloid leukemia. She achieved an excellent visual outcome following intensive antifungal therapy.
Topics: Antifungal Agents; Child; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Immunocompromised Host; Scedosporium; Treatment Outcome
PubMed: 24210343
DOI: 10.1016/j.jaapos.2013.07.010 -
Clinical Infectious Diseases : An... Jun 2001Scedosporium prolificans infection was analyzed in 18 patients from whom the fungus was isolated during the period 1990-1999. Of these 18 patients, 12 had some... (Review)
Review
Scedosporium prolificans infection was analyzed in 18 patients from whom the fungus was isolated during the period 1990-1999. Of these 18 patients, 12 had some predisposing factor and either unconfirmed infection or colonization, and 6 patients had confirmed disseminated infection: 4 patients with leukemia died, 1 patient with breast cancer who underwent autologous bone marrow transplantation survived, and 1 patient with advanced acquired immunodeficiency syndrome died, although the fungal infection did not seem to affect his clinical symptoms.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Mycetoma; Retrospective Studies; Scedosporium
PubMed: 11340550
DOI: 10.1086/320521 -
Revista Chilena de Infectologia :... Jun 2012
Topics: Scedosporium
PubMed: 23096475
DOI: 10.4067/S0716-10182012000300014 -
Emerging infectious endocarditis due to Scedosporium prolificans: a model of therapeutic complexity.European Journal of Clinical... Nov 2011Scedosporium prolificans is an emerging agent for severe infections. Although among the dematiaceous fungi Scedosporium is the most frequently isolated in blood... (Review)
Review
Scedosporium prolificans is an emerging agent for severe infections. Although among the dematiaceous fungi Scedosporium is the most frequently isolated in blood cultures, Scedosporium endocarditis is rarely reported. We show herein a patient with acute leukaemia who developed S. prolificans endocarditis. Twelve cases were found in an extensive review of the English literature. In six cases (46%), there was predisposing heart conditions such as a prosthetic valve or an intracavitary device. Only 4 patients (31%) were immunocompromised hosts with haematologic neoplasia, solid-organ transplantation or acquired immunodeficiency syndrome (AIDS). Exposure to Scedosporium was observed in immunocompetent patients who developed infection while in the community. Scedosporium endocarditis occurred on both sides of the heart. Systemic and pulmonary emboli and other metastatic complications were seen in all of these patients. The overall mortality was 77% and, specifically, all of the immunocompromised hosts and 6 out of 7 patients with mitral or aortic valve endocarditis died. Patients with right-sided endocarditis associated with a removable intracardiac device exhibited a better prognosis. Scedosporium endocarditis, although still rare, is an emerging infection with an ominous prognosis. At the present time, valve replacement or the removal of cardiac devices plus combined antifungal treatment may offer the best possibility of cure.
Topics: Adult; Amphotericin B; Antifungal Agents; Communicable Diseases, Emerging; Embolectomy; Endocarditis; Fatal Outcome; Female; Femoral Artery; Humans; Immunocompromised Host; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Pyrimidines; Scedosporium; Thrombosis; Tomography, X-Ray Computed; Triazoles; Voriconazole
PubMed: 21455664
DOI: 10.1007/s10096-011-1212-3 -
Antimicrobial Agents and Chemotherapy Sep 2022Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates....
EUCAST-Obtained Olorofim MICs against Aspergillus and Scedosporium Species and Lomentospora prolificans Showed High Agreements between Visual Inspection and Spectrophotometric Readings.
Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates. Here, we tested and compared the activity of a novel antifungal, olorofim, against Aspergillus spp., spp., and Lomentospora prolificans by visual inspection and spectrophotometric readings. Clinical isolates of Aspergillus ( = 686) and ( = 36) spp. and ( = 13) were tested. Olorofim MICs were evaluated-following the EUCAST E.Def 9.4 procedure-by visual inspection or spectrophotometric readings (combinations of either ≥90% or ≥95% fungal growth inhibition endpoints compared to drug-free control endpoints and different wavelengths [405 nm, 450 nm, 492 nm, 540 nm, and 620 nm]). We observed high activity of olorofim against all tested Aspergillus spp. (MICs up to 0.06 mg/L), except for A. calidoustus, and against and spp. (MICs up to 0.125 mg/L). The combination of ≥90% fungal growth inhibition endpoints at wavelengths of ≥492 nm resulted in high essential agreements with A. fumigatus and lesser agreement with non- Aspergillus, spp., and , although the number of isolates studied was low. This single-center study shows high agreement among olorofim MICs against A. fumigatus by visual inspection and spectrophotometric readings (≥90% fungal growth inhibition endpoints and wavelengths of ≥492 nm) and encouraging results against non- Aspergillus spp., spp., and .
Topics: Acetamides; Amphotericin B; Antifungal Agents; Aspergillus; Piperazines; Pyrimidines; Pyrroles; Scedosporium
PubMed: 35924916
DOI: 10.1128/aac.00849-22