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At least 19 recordsLinked to original sources
PubMed2004

Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome.

BACKGROUND: Unique characteristics, impact of therapy with antifungal agents, and outcome of infections with Scedosporium species were assessed in transplant recipients. METHODS: The patients comprised a total of 80 transplant recipients with Scedosporium infections, including 13 patients from our institutions (University of Pittsburgh Medical Center [Pittsburgh, PA], University of Maryland [Baltimore], Duke University Medical Center [Durham, NC], Emory University [Atlanta, GA], and Hospital Gregorio Maranon [Madrid, Spain]) and 67 reported in the literature. The transplant recipients were compared with 190 non-transplant recipients with scedosporiosis who were described in the literature. RESULTS: Overall, 69% of the infections in hematopoietic stem cell transplant (HSCT) recipients and 53% of the infections in organ transplant recipients were disseminated. HSCT recipients, compared with organ transplant recipients, were more likely to have infections caused by Scedosporium prolificans (P=.045), to have an earlier onset of infection (P=.007), to be neutropenic (P<.0001), and to have fungemia (P=.04). Time elapsed from transplantation to Scedosporium infection in transplant recipients has increased in recent years (P=.002). The mortality rate among transplant recipients with scedosporiosis was 58%. In a logistic regression model using amphotericin B as comparison treatment, voriconazole was associated with a trend towards better survival (odds ratio [OR], 10.40; P=.08). Presence of disseminated infection (OR, 0.20; P=.03) predicted lower survival, and receipt of adjunctive surgery as treatment (OR, 5.52; P=.02) independently predicted a better survival in this model. CONCLUSIONS: Scedosporium infections in transplant recipients were associated with a high rate of dissemination and a poor outcome overall. The use of newer triazole agents warrants consideration as a therapeutic modality for these infections.

Adolescent↗
PubMed2001

Scedosporium endophthalmitis: two fatal disseminated cases of Scedosporium infection presenting with endophthalmitis.

The incidence of disseminated infection with Scedosporium species is increasing in patients with haematological malignancy. Two fatal cases are reported of patients with acute myeloid leukaemia and neutropenia who presented with Scedosporium endophthalmitis. Diagnosis of fungal infection was delayed as blood and vitreous cultures were positive only after 3 days in patient 1 and blood culture was positive at 7 days in patient 2. Despite antifungal therapy with amphotericin B and additional fluconazole in patient 2, both patients died of overwhelming fungal septicaemia. Post-mortem examination of the right globe in patient 1 showed haemorrhagic necrotizing chorioretinitis with numerous fungal hyphae in choroidal vessels, choroid, retina and vitreous. Scedosporium species are often resistant to conventional antifungal therapy including amphotericin B. Diagnosis is difficult and mortality in disseminated infection is high.

Acute Disease↗
PubMed2002

Amphotericin B lipid complex exerts additive antifungal activity in combination with polymorphonuclear leucocytes against Scedosporium prolificans and Scedosporium apiospermum.

Scedosporium prolificans and Scedosporium apiospermum are resistant to most antifungal agents and cause refractory pulmonary and disseminated infections. The combined effects of deoxycholate amphotericin B, amphotericin B lipid complex and liposomal amphotericin B with human polymorphonuclear leucocytes (PMNs) in damaging hyphae of these fungi were evaluated by XTT assay. Amphotericin B lipid complex displayed a significant additive effect with PMNs against both Scedosporium species (22% for S. prolificans and 81% for S. apiospermum; P < 0.04). None of the formulations adversely affected the PMN antifungal activity. These findings may be important in designing better strategies for management of infections due to these organisms.

Adult↗
PubMed2002

Antifungal triazoles and polymorphonuclear leukocytes synergize to cause increased hyphal damage to Scedosporium prolificans and Scedosporium apiospermum.

Scedosporium prolificans and Scedosporium apiospermum (Pseudallescheria boydii) cause pulmonary and disseminated infections refractory to most currently used antifungal agents in immunocompromised patients. We therefore investigated the potential antifungal activities of the triazoles itraconazole (ITC), voriconazole (VRC), and posaconazole (PSC) in combination with human polymorphonuclear leukocytes (PMNs) against the hyphae of these fungal pathogens. A colorimetric assay with (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide) sodium salt was used for the measurement of hyphal damage as an indicator of antifungal activity. We found that the newer triazoles VRC and PSC displayed synergistic effects with PMNs against S. prolificans hyphae after 24 h (P < 0.05), whereas the effect of ITC in combination with PMNs was additive (P < 0.01). All three triazoles displayed additive antifungal activities in combination with PMNs against S. apiospermum hyphae (P < 0.05). The synergistic or additive effects that these triazoles exhibited, combined with the antifungal activities of human PMNs, may have important therapeutic implications for the management of infections due to S. prolificans and S. apiospermum.

Adult↗
PubMed1995

Fatal meningoencephalitis caused by Scedosporium inflatum (Scedosporium prolificans) in a child with lymphoblastic leukemia.

A fatal case of meningoencephalitis caused by Scedosporium inflatum (Scedosporium prolificans) in a 5-year-old boy with acute myeloblastic leukemia who was given intrathecal treatment is reported. Itraconazole treatment was ineffective. The fungus was identified on brain sections at autopsy and was not observed in any other organ. As no other portal of entry was detected, meningoencephalitis may have originated via direct introduction of the fungus at therapeutic lumbar puncture.

Child, Preschool↗
PubMed1999

Comparative in-vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum.

We report the in-vitro susceptibility of 27 clinical isolates of Scedosporium apiospermum and 43 of Scedosporium prolificans. S. apiospermum was resistant to fluconazole and flucytosine, with variable susceptibility to amphotericin B, itraconazole, ketoconazole and susceptible to miconazole. Voriconazole was much more active than fluconazole and flucytosine, more active than amphotericin B, itraconazole and ketoconazole and was as active as miconazole against S. apiospermum isolates. Voriconazole and the other six antifungal agents showed low activity against S. prolificans isolates.

Antifungal Agents↗
PubMed1997

Deep infections caused by Scedosporium prolificans. A report on 16 cases in Spain and a review of the literature. Scedosporium Prolificans Spanish Study Group.

Scedosporium prolificans, a mold morphologically similar to Scedosporium apiospermum, may cause asymptomatic colonization or localized or disseminated infection following trauma, surgery, and immunosuppression. S. prolificans is normally resistant to available antifungal agents, and prognosis depends largely on the host's immune status, extent of infection, and feasibility of surgical debridement. We report on 16 patients with deep S. prolificans infections, focusing on predisposing factors, clinical characteristics, outcome, postmortem findings, and antifungal susceptibility testing to 6 antifungal agents. Between 1989 and 1994, 16 cases of deep infections by S. prolificans were documented in 6 clinical centers in Spain (15 adults and 1 child: male/female = 0.77). Fifteen patients had underlying hematologic malignancy (14 with neutropenia) and 1 had a prosthetic cardiac valve. Syndromes included disseminated infection in 14 patients (1 with prosthetic valve endocarditis) and fungal pneumonia and meningoencephalitis in 1 patient each. S. prolificans was isolated from 2 specimens in 14 patients and from 1 specimen in 2 patients (blood, n = 12; respiratory tract, n = 4; CNS, n = 4; and skin biopsy, n = 3). Antifungal susceptibility testing by a micromethod with RPMI-2% glucose medium was performed in 8 isolates, all of which were resistant to amphotericin B, flucytosine, ketoconazole, fluconazole, itraconazole, and miconazole. All patients received antifungal therapy (amphotericin B, n = 9; amphotericin B+ flucytosine, n = 1; amphotericin B+ itraconazole, n = 2; liposomal amphotericin B+ itraconazole, n = 1; amphotericin B+ fluconazole, n = 1 and 2 underwent surgical procedures. Two patients survived coinciding with hematologic recovery and 14 (87.5%) patients died in a median time of 4 days after the first positive culture (range, 0-60 d). Necropsy was performed in 10 patients, and disseminated infection was found in 9. In conclusion, S. prolificans is an emerging multiresistant fungal pathogen that may cause asymptomatic colonization, localized infection related to trauma or surgery, and rapidly fatal disseminated infection in immunocompromised hosts, particularly those with neutropenia. This mycosis underscores the urgent need for new antifungal agents.

Adolescent↗
PubMed2001

Pulmonary scedosporium infection following lung transplantation.

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

Adult↗
PubMed2005

Inteferon gamma and granulocyte-macrophage colony-stimulating factor augment the antifungal activity of human polymorphonuclear leukocytes against Scedosporium spp.: comparison with Aspergillus spp.

While Aspergillus spp. have been the most frequent filamentous fungi causing infections in immunocompromised patients, Scedosporium spp. are emerging as life-threatening pathogens. We studied the effects of interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or combined on the antifungal activities of human polymorphonuclear leukocytes (PMN) against Scedosporium apiospermum and Scedosporium prolificans. We paralleled these activities to those against Aspergillus fumigatus and Aspergillus flavus. Incubation of PMN with IFN-gamma and GM-CSF for 22 h enhanced PMN-induced hyphal damage of both Aspergillus spp. and S. prolificans (p < 0.05) but not of S. apiospermum. However, hyphae of S. apiospermum were damaged significantly more after incubation with PMN that had been treated with IFN-gamma and GM-CSF for 2 h. In addition, incubation of PMN with GM-CSF for 2 h enhanced PMN oxidative burst measured as superoxide anion (O2-) production in response to nonopsonized hyphae of A. flavus and Scedosporium spp. (p < 0.05). In contrast, after 2 h, IFN-gamma and GM-CSF alone did not enhance PMN O2- in response to opsonized hyphae of A. flavus and Scedosporium spp.; however, the combination of IFN-gamma and GM-CSF showed significant enhancement against these species. Thus, IFN-gamma and GM-CSF, particularly in combination, demonstrate a species- and time-dependent augmentation of PMN responses to Scedosporium spp.

Aspergillus flavus↗
PubMed1998

Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydii): an emerging mycosis.

The genus Scedosporium contains two medically significant species of emerging mycotic agents, S. apiospermum and S. prolificans, which have received scant attention. Scedosporium apiospermum is the anamorph, or asexual state, of the cosmopolitan fungus Pseudallescheria boydii, with both sharing the same risk factors for infection, clinical spectrum, and histopathologic features. Scedosporium prolificans is a recently recognized agent of bone, soft tissue, and joint infections that occurs with highest frequency in children and young adults. S. prolificans may also cause potentially fatal disseminated infections in immunocompromised persons. The drug sensitivities of both Scedosporium species are significantly different from those of most other fungi, and thus identification of these organisms is important. Unfortunately, the pathological features of Scedosporium infections may be easily confused with other mycotic agents, resulting in delayed or inappropriate medical therapy. Because many pathologists and clinicians are unfamiliar with the significance of Scedosporium spp. infection, this communication describes three persons with differing clinical and pathological presentations of S. apiospermum infection. In one patient with sickle cell disease and chronic mycotic sinusitis, fungal colonies of S. apiospermum removed from the sinuses showed a pattern of alternating zones of mycelial hypercellularity and hypocellularity associated with conidiation, similar to a previous report of P. boydii infection. The clinicopathologic features of an immunocompetent person with S. apiospermum osteomyelitis, and a patient with S. apiospermum infection of the brain after bone marrow transplantation, are also described.

Adult↗
PubMed2003

Successful control of disseminated Scedosporium prolificans infection with a combination of voriconazole and terbinafine.

Disseminated Scedosporium prolificans infections are almost uniformly fatal because of their resistance to antifungal agents. Recently, synergy between triazoles and terbinafine has been demonstrated against Scedosporium prolificans in vitro. Reported here is a patient who developed disseminated Scedosporium prolificans infection following bone marrow transplantation and who was successfully treated with a combination of voriconazole and terbinafine in addition to aggressive surgical debridement. Antifungal synergy testing and combination therapy should be considered in cases of disseminated infection with Scedosporium prolificans.

Antifungal Agents↗
PubMed2006

Scedosporium infection in a tertiary care cancer center: a review of 25 cases from 1989-2006.

We reviewed the records of patients with cancer who had Scedosporium infection (due to Scedosporium apiospermum and Scedosporium prolificans in 21 and 4 patients, respectively). The incidence of Scedosporium infection increased from 0.82 cases per 100,000 patient-inpatient days (in 1993-1998) to 1.33 cases per 100,000 patient-inpatient days (in 1999-2005). Cases of S. prolificans infection occurred only after 2000. Dissemination occurred in 16 patients (64%). The 12-week mortality rates were 70% and 100% for S. apiospermum and S. prolificans infection, respectively.

Adult↗
PubMed2001

Molecular epidemiology of Scedosporium apiospermum infection determined by PCR amplification of ribosomal intergenic spacer sequences in patients with chronic lung disease.

Respiratory tract colonization with Scedosporium apiospermum in patients with chronic suppurative lung disease is a significant concern for lung transplantation candidates, since Scedosporium infections occurring posttransplantation are usually untreatable. Up to 10% of patients with cystic fibrosis attending our respiratory medicine unit have had Scedosporium organisms isolated from sputum samples. We therefore developed a molecular typing method to examine these isolates. Typing by PCR amplification of ribosomal intergenic spacer sequences demonstrated 20 different types from 52 isolates collected from the respiratory medicine unit and elsewhere in Australia. A single common type was isolated from 11 respiratory medicine unit inpatients. Two other types were isolated from more than one source: one from two respiratory medicine unit inpatients and one from two epidemiologically linked nonhuman sources. Multiple isolates were obtained from nine patients. This method demonstrated persistent carriage of isolates of the same type in one patient for 7 months. Two patients showed carriage of isolates with multiple typing patterns within a 3-month period. The high rate of isolation and the predominance of isolates with a single typing pattern from respiratory medicine unit patients may suggest transmission to patients from a source in the unit. There was no epidemiological evidence of direct patient-to-patient spread, and Scedosporium organisms were not isolated from dust, soil, or air samples from the unit. The source and route of transmission have yet to be determined.

Adult↗
PubMed2003

Scedosporium prolificans osteomyelitis in an immunocompetent child treated with voriconazole and caspofungin, as well as locally applied polyhexamethylene biguanide.

Scedosporium species are increasingly isolated from immunocompromised and immunocompetent patients. Unfortunately, Scedosporium infections are generally resistant to amphotericin B, and Scedosporium prolificans strains are particularly resistant to the antifungal agents now in use. We report here on an immunocompetent child with S. prolificans-associated osteomyelitis successfully treated with debridement, local irrigation with polyhexamethylene biguanide, and the systemic administration of voriconazole and caspofungin despite poor in vitro activity of voriconazole alone against the isolate. We also review the treatments and outcomes of 28 reported cases of osteomyelitis or septic arthritis caused by Scedosporium species in immunocompetent patients.

Administration, Topical↗
PubMed2003

Scedosporium species infections and treatments.

Scedosporium species are now increasingly isolated from immunocompromised and immunocompetent patients. Unfortunately, Scedosporium species infections are generally resistant to amphotericin B, and S. prolificans strains are particularly resistant to presently-available antifungal agents. Here we review the microbiology, expanding epidemiology, numerous clinical presentations, and diagnostic tools available for Scedosporium species infections. Finally, we detail the available in vitro, animal model, and clinical data on the treatment of Scedosporium species infections with special emphasis on the role of newer antifungal therapies for these recalcitrant infections.

Antifungal Agents↗
PubMed1991

Disseminated Scedosporium inflatum infection in a patient with acute myeloblastic leukemia.

A case of disseminated Scedosporium inflatum infection occurring in a neutropenic patient with acute myeloblastic leukemia is reported. Scedosporium inflatum was isolated from skin lesions, blood, urine and vitreous cultures. Amphotericin B treatment was ineffective in avoiding hematogenous spread. At autopsy, hyphae and ovoid conidia with truncate bases consistent with the morphology of Scedosporium inflatum were found in the lungs, kidneys, myocardium, liver, thyroid, spleen, lymph nodes, brain and the left eye. This is the first report of disseminated Scedosporium inflatum infection and the first time this organism has been isolated from a patient in Europe.

Aged↗
PubMed2000

Clinical significance of Scedosporium apiospermum in patients with cystic fibrosis.

The incidence of airway colonization by Scedosporium apiospermum and of related sensitization was investigated prospectively in 128 patients with cystic fibrosis over a 5-year period, and results were compared with clinical data. Scedosporium apio-spermum, recovered from sputum samples in 11 of 128 (8.6%) patients, was the most frequent filamentous fungus after Aspergillus fumigatus. Counterimmuno-electrophoresis, used to detect scedosporiosis serologically, was positive in 27 of 128 (21.1%) patients. The discrepancy between the mycological and serological results may be related to immune cross-reactions between Scedosporium apiospermum and Aspergillus fumigatus. However, symptoms of allergic bronchopulmonary disease were observed in two patients chronically colonized by Scedosporium apiospermum. The results clearly demonstrate that the frequency of this fungus is largely underestimated and that it may trigger an inflammatory response, thus suggesting a pathogenic role in patients with cystic fibrosis.

Adolescent↗
PubMed2001

Scedosporium infection in immunocompromised patients: successful use of liposomal amphotericin B and itraconazole.

BACKGROUND: Invasive fungal disease is a major cause of death in immunocompromised patients. The filamentous fungus Scedosporium consists of two species, S. prolificans and S. apiospermum, which can cause infections in immunocompromised patients that are often fatal. A significant feature of this pathogen is its broad resistance to many antifungal agents, including amphotericin B. PROCEDURE AND RESULTS: Five cases of infection with Scedosporium spp. occurred in patients with haematologic malignancies over a 10-month period. Three patients with S. prolificans were severely immunosuppressed and neutropenic; two were in relapse and another was early post-matched unrelated bone marrow transplant. All three died despite treatment with various combinations of amphotericin B and itraconazole. Two patients who were less immunosuppressed and had a normal neutrophil count developed S. apiospermum infection. Both were successfully treated with liposomal amphotericin B and itraconazole. CONCLUSIONS: Disseminated infection in immunocompromised hosts with Scedosporium spp. is often fatal. However, in patients with a lesser degree of immunocompromise and particularly in those infected with the less virulent S. apiospermum, intensive antifungal therapy with liposomal amphotericin B and itraconazole may be associated with complete eradication of infection. Med Pediatr Oncol 2001;37:122-125.

Adolescent↗