Disseminated Scedosporium Prolificans Infection and Survival of a Child With Acute Lymphoblastic Leukemia

Whyte, Morag; Irving, Helen; O'Regan, Peter; Nissen, Michael; Siebert, David; Labrom, Robert D.

doi:10.1097/01.inf.0000157213.94392.30

Cited by 32 publications

(20 citation statements)

References 17 publications

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“…The most common isolate was S. prolificans, accounting for over a third of cases. Since that review, S. prolificans remains the most frequent cause of disseminated disease, almost exclusively in immunocompromised patients (33,62,96,151,304,358,364,368,434,697,709,747,750,796). E. dermatitidis, in contrast, is commonly seen in immunocompetent patients, particularly from Asia (13,349,565).…”

Section: Phaeohyphomycosismentioning

confidence: 99%

“…There were no antifungal regimens associated with improved survival for disseminated infection. Scedosporium prolificans is generally resistant to all available antifungal agents, and infection with S. prolificans was associated with nearly 100% mortality in the absence of recovery from neu- (358,750,796). Some case reports utilized colony-stimulating factors and/or leukocyte infusions to augment antifungal therapy (96,368,796).…”

Section: Phaeohyphomycosismentioning

confidence: 99%

“…Scedosporium prolificans is generally resistant to all available antifungal agents, and infection with S. prolificans was associated with nearly 100% mortality in the absence of recovery from neu- (358,750,796). Some case reports utilized colony-stimulating factors and/or leukocyte infusions to augment antifungal therapy (96,368,796). Other combinations or therapies have not been shown to be consistently effective, though clinical experience is limited, and will likely be confined to anecdotal reports, given the rarity of this infection.…”

Section: Phaeohyphomycosismentioning

confidence: 99%

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Melanized Fungi in Human Disease

2010

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SUMMARY Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.

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Section: Phaeohyphomycosismentioning

confidence: 99%

Section: Phaeohyphomycosismentioning

confidence: 99%

Section: Phaeohyphomycosismentioning

confidence: 99%

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Melanized Fungi in Human Disease

2010

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“…are among the most antifungal drug-resistant organisms encountered in clinical practice (1,2,7,21,25,32,38). Optimal treatment against infection with these fungal pathogens has not been established, and anecdotal successes have been reported with various agents alone or in combination (4,12,14,18,20,23,26,33,34,40).…”

mentioning

confidence: 99%

Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods

Castanheira

Duncanson

Diekema

et al. 2012

Antimicrob Agents Chemother

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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 (g/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 g/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC 90 was 0.12 g/ml for S. apiospermum, but 1 to >8 g/ml for other tested agents. Against S. aurantiacum, the MEC 50 for E1210 was 0.06 g/ml versus 0.5 to >8 g/ml for the comparators. Against S. prolificans, the MEC 90 for E1210 was only 0.12 g/ml, compared to >4 g/ml for amphotericin B and >8 g/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.

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“…21,31 Since the first case of scedosporiosis reported in acute leukemia in 1977, 32 hematologists have shown a growing interest in this pathogen, particularly over the last decade. Both our literature review and our case series demonstrated that, among patients affected by hematologic malignancies, those affected by AML are at the highest risk, usually during a period of chemotherapy induced severe neutropenia.…”

confidence: 99%

Scedosporiosis in patients with acute leukemia: a retrospective multicenter report

Caira¹,

Girmenia²,

Valentini³

et al. 2008

Haematologica

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We retrospectively analyzed 542 proven/probable mould infections registered, in the course of 2 studies, in 8,633 patients with acute leukemia, focusing on scedosporiosis. We aimed to define scedosporiosis incidence and mortality rate over a 15-year period. Only 5 cases of scedosporiosis were identified, all of them involving patients with acute myeloid leukemia (AML). We also reviewed all cases of Scedosporium spp. infections in acute leukemia reported to date in the international literature. The 52 cases analyzed confirmed that acute myeloid leukemia is the category with the highest risk of scedosporiosis. Clinical features of scedosporiosis were extremely variable and closely related to patient immune status. Infection disseminated to multiple sites in a very high percentage of patients and outcome was confirmed to be very poor. In our surveys all patients died, in spite of Amphotericin B compounds or voriconazole administration. Our review of literature found scedosporiosis attributable mortality rate (AMR) to be 77%. In conclusion, scedosporiosis, although extremely rare, represents a big problem for clinicians because of its aggressive clinical presentation and the lack of an effective therapy. New drugs with in vitro activity against Scedosporium spp (voriconazole, posaconazole) should be considered. However, their clinical activity should be more widely demonstrated.

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Disseminated Scedosporium Prolificans Infection and Survival of a Child With Acute Lymphoblastic Leukemia

Cited by 32 publications

References 17 publications

Melanized Fungi in Human Disease

Melanized Fungi in Human Disease

Activities of E1210 and Comparator Agents Tested by CLSI and EUCAST Broth Microdilution Methods against Fusarium and Scedosporium Species Identified Using Molecular Methods

Scedosporiosis in patients with acute leukemia: a retrospective multicenter report

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