Detection of (1→3)-β-
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            -Glucan as an Adjunct to Diagnosis in a Mixed Population with Uncommon Proven Invasive Fungal Diseases or with an Unusual Clinical Presentation

Cuétara, María Soledad; Alhambra, Almudena; Moragues, Marı́a D.; González-Elorza, Ernesto; Pontón, José; Palacio, Amalia del

doi:10.1128/cvi.00009-09

Cited by 55 publications

(29 citation statements)

References 12 publications

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“…We found a correlation between the decrease in the marker, the fungal load, and the dose administered. Until now, the detectable levels of (1-3)-␤-D-glucan have been used for diagnosis, although the relationship between such antigen levels and the fungal load found in the present study and in previous studies on animal models (9,33) seems to indicate that (1-3)-␤-D-glucan levels might be useful for evaluating prognosis in infections with S. capitata. Further studies are needed to confirm this finding.…”

Section: Discussioncontrasting

confidence: 47%

“…This reduction was dose dependent and correlated with the levels of drug detected in serum after the end of the treatment. The (1-3)-␤-Dglucan marker is a cell wall component that is common in the fungal kingdom, easily detectable, and quantifiable in serum and body fluids, and it is used as a marker of disseminated fungal infections, including those caused by S. capitata (9,33). We found a correlation between the decrease in the marker, the fungal load, and the dose administered.…”

Section: Discussionmentioning

confidence: 70%

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Efficacy of Posaconazole in a Murine Model of Systemic Infection by Saprochaete capitata

Thomson

Guarro

Mayayo

et al. 2015

Antimicrob Agents Chemother

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The fungus Saprochaete capitata causes opportunistic human infections, mainly in immunocompromised patients with hematological malignancies. The best therapy for this severe infection is still unknown. We evaluated the in vitro killing activity and the in vivo efficacy of posaconazole at 5, 10, or 20 mg/kg twice a day (BID) in a murine neutropenic model of systemic infection with S. capitata by testing a set of six clinical isolates. Posaconazole showed fungistatic activity against all of the isolates tested. The different doses of the drug, especially the highest one, showed good efficacy, measured by prolonged survival, reduction of (1-3)-␤-D-glucan levels in serum, tissue burden reduction, and histopathology. Saprochaete capitata, formerly known as Trichosporom capitatum, Geotrichum capitatum, and Blastoschizomyces capitatus, is an uncommon clinical fungus belonging to the phylum Basidiomycota, but it is able to cause fatal fungemia in immunocompromised patients, especially in those with hematological malignancies (1-6). The therapeutic options against these infections are limited, because S. capitata is considered intrinsically resistant to the echinocandins (7-10). Currently, there are no recommendations for the management of infections caused by S. capitata, although amphotericin B is the drug most commonly used in the clinical setting, followed by itraconazole and voriconazole (9,(11)(12)(13)(14). The use of these compounds is supported by the in vitro antifungal susceptibility of S. capitata to such drugs. However, despite treatment, the mortality rate still remains high, at around 60% (5, 15-19), making it necessary to explore new therapeutic approaches. In previous studies conducted on mice, high doses of fluconazole demonstrated higher efficacy than amphotericin B, flucytosine, and voriconazole (20). Posaconazole has not been evaluated against this fungal species before but has shown efficacy in experimental infections against a wide range of opportunistic fungi, such as Aspergillus spp., Curvularia spp., Rhizopus oryzae (21,22,23), and others, including Trichosporon asahii, which is taxonomically related to S. capitata (24). In the present study, we evaluated the in vitro killing activity of posaconazole against this fungus as well as its in vivo efficacy in a neutropenic murine model of systemic infection by S. capitata. (IHEM 5665, IHEM 5666, IHEM 5091, IHEM 6803, IHEM 16105, and IHEM 16109) were included in this study. The inocula were prepared from potato dextrose agar (PDA) cultures by flooding the plates with 3 ml of sterile saline solution and scraping the surface of the colonies with a loop in order to obtain a conidial suspension. To remove hyphal fragments and clumps of agar, the resulting suspension was filtered twice through sterile gauze and then adjusted by hemocytometer counts to the desired concentrations. Viability of inocula was determined by placing 10-fold dilutions of the conidial suspension on PDA plates. MATERIALS AND METHODS Strains and inocula. Six clinical strains of S. ca...

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 70%

Efficacy of Posaconazole in a Murine Model of Systemic Infection by Saprochaete capitata

Thomson

Guarro

Mayayo

et al. 2015

Antimicrob Agents Chemother

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“…and galactomannan (primarily for Aspergillus spp.) may cross-react with melanized fungi, though usually with low levels (164,419). However, in immunocompromised patients with cultures positive for dematiaceous fungi, a positive serum galactomannan test may indicate concomitant infection with Aspergillus; careful clinical correlation is advised (71).…”

Section: Antigen Testing and Serologymentioning

confidence: 99%

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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“…Its detection in serum assists in diagnosis of invasive fungal infections (1). Recently, diagnostic challenge has arisen in the fungal meningitis outbreak associated with exposure to contaminated epidural steroid injections (2).…”

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confidence: 99%

Cerebrospinal Fluid (1,3)-β- d -Glucan Detection as an Aid for Diagnosis of Iatrogenic Fungal Meningitis

et al. 2013

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f This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)-␤-D-glucan in cerebrospinal fluid during the current U.S. outbreak of fungal meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients.(1,3)-␤-D-glucan (BG) is found in cell walls of multiple fungi. Its detection in serum assists in diagnosis of invasive fungal infections (1). Recently, diagnostic challenge has arisen in the fungal meningitis outbreak associated with exposure to contaminated epidural steroid injections (2). Diagnosis in this setting has been established by culture of cerebrospinal fluid (CSF) and/or detection using a pan-fungal PCR assay performed by the Centers for Disease Control (CDC). However, these tests have not always been positive in suspected cases (3). One early study has demonstrated the proof of concept of using CSF BG detection in diagnosis of fungal central nervous system infection in an experimental hematogenous Candida meningoencephalitis model (4). Here we report our experience with CSF BG measurement in 5 individuals from Johns Hopkins Hospital and Indiana University Hospital who were exposed to potentially contaminated drugs. Cases were diagnosed and managed according to CDC guidelines. BG was tested at Beacon Diagnostics Laboratory (East Falmouth, MA) using the Fungitell assay. Information was obtained by chart review with approval from the Johns Hopkins Institutional Review Board.The first case was a 55-year-old woman who developed headaches, blurred vision, and injection site pain 1 week after lumbar epidural injection with potentially contaminated methylprednisolone and was admitted 35 days after symptom onset when the outbreak was recognized. CSF showed 30 white blood cells (WBCs)/mm 3 and normal glucose and protein; no opening pressure was recorded. Intravenous voriconazole was initiated, but symptoms continued despite troughs of 2 to 3 g/ml. Repeat lumbar puncture (LP) showed opening pressure of 42 cm H 2 O, 974 WBC/mm 3 (56% neutrophils, 16% lymphocytes, 21% monocytes), 1,000 red blood cells (RBCs)/mm 3 , normal glucose, and 93 mg/dl protein, with a negative culture. CSF PCR performed by the CDC was negative. With serial LPs for persistent headache and elevated opening pressures and voriconazole increase to maintain troughs of 3 to 5 g/ml, her symptoms resolved. CSF fungal cultures from postinjection days 57, 69, and 73 were negative. CSF BG samples sent on postinjection days 57 and 73 were positive at 2,396 and 701 pg/ml, respectively (Table 1).The second case was a 37-year-old man who underwent lumbar epidural injection with potentially contaminated methylprednisolone and developed a headache several days later. Thirteen days after the injection he started oral voriconazole. His symptoms did not improve, and LP 2 weeks later showed 5 WBCs/mm 3 ( Table 1). PCR performed by the CDC and fungal cultures were negative. Magnetic resonance imaging (MRI) of the brain showed a small intrapa...

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Detection of (1→3)-β- d -Glucan as an Adjunct to Diagnosis in a Mixed Population with Uncommon Proven Invasive Fungal Diseases or with an Unusual Clinical Presentation

Cited by 55 publications

References 12 publications

Efficacy of Posaconazole in a Murine Model of Systemic Infection by Saprochaete capitata

Efficacy of Posaconazole in a Murine Model of Systemic Infection by Saprochaete capitata

Melanized Fungi in Human Disease

Cerebrospinal Fluid (1,3)-β- d -Glucan Detection as an Aid for Diagnosis of Iatrogenic Fungal Meningitis

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