A 15-year-old boy with acute lymphoblastic leukemia (ALL) developed disseminated fusarium infection with meningoencephalitis following a contaminated skin wound. With antifungal therapy, the cutaneous lesions cleared but central nervous system (CNS) infection persisted causing a fibrosing meningitis and a brain granuloma. Fusaria are soil saprophytes that are more commonly associated with superficial eye and skin lesions, but may also cause severe systemic infections with CNS involvement in immuno-compromised patients. The organism may be confused with Aspergillus in tissue sections, and can only be diagnosed by culture.

OBJECTIVES: To analyse the susceptibility pattern of a collection of Fusarium clinical isolates. METHODS: The antifungal susceptibility pattern of 67 isolates of Fusarium was analysed. Strains were identified by morphological and molecular methods by means of sequencing elongation factor alpha. RESULTS AND CONCLUSIONS: Six different species were identified. Fusarium solani was the most frequently isolated, followed by Fusarium oxysporum, Fusarium proliferatum and Fusarium verticilloides. Amphotericin B was the only drug with in vitro activity (range: 0.015-32 mg/L). The rest of the antifungals tested (itraconazole, voriconazole, ravuconazole, posaconazole and terbinafine) showed very poor activity against Fusarium, confirming the multiresistant nature of this genus.

The diagnosis of invasive fungal infections (IFI) remains a challenge, particularly for diseases caused by filamentous fungi such as Aspergillus species. Unfortunately, many patients affected by these conditions are not identified before autopsy. Therefore, there is a need for new diagnostic methods for IFI. Galactomannan is a soluble antigen released during hyphal growth in tissues. A commercially available sandwich ELISA assay that detects galactomannan has been used in Europe for many years and is now approved for use in the USA. The test has an excellent negative predictive value in the detection of invasive aspergillosis (IA) in high-risk patients. In addition, it is more sensitive than culture and allows IA to be diagnosed before clinical manifestations occur. However, false-negative and false-positive results in certain populations are the main limitations to its use. The purpose of this review is to summarize the current knowledge about galactomannan testing in patients at risk for IA.

Subcutaneous granulomatous lesions by hyaline moulds are rare. This report describes a case of hyalohyphomycosis by Fusarium oxysporum. The patient was a 16-year-old Sri Lankan girl who had had extensive lesions in both arms almost from infancy. The fungus was demonstrated in KOH mounts and in histopathological sections. It was isolated repeatedly from her lesions over a period of 10 months. Combined therapy with ketoconazole and 5-fluorocytosine resulted in marked improvement. An inherent immune defect is postulated to account for the prolonged and extensive infection by a relatively non-aggressive fungus.

We report the case of a 30-year-old Nigerian patient with mycetoma of the foot without bone involvement caused by Fusarium sp..Long-term administration of ketoconazole produced a significant improvement with good clinical and biological tolerance.

Infections caused by Fusarium species are increasing in frequency among immunocompromised hosts. We identified 35 patients with cancer who had Fusarium skin lesions. Twenty patients had disseminated infection, 6 had primary localized skin infections, 4 had skin lesions associated with sinus infections, and 5 had onychomycosis. All patients (except 3 with onychomycosis) had hematologic malignancies and neutropenia. Skin lesions associated with disseminated infection included red or gray macules, papules (some with central necrosis or eschar), pustules, and subcutaneous nodules. Most patients had a variety of lesions simultaneously. Multiple red or gray macules with central ulceration or black eschar are characteristic of Fusarium infection. Disseminated infection may originate from skin lesions or onychomycosis. Most infections fail to respond to antifungal therapy unless there is resolution of the patient's neutropenia.

Disseminated fungal infections commonly occur in immunocompromised hosts; Candida spp. are the most common. Fusarium spp., soil saprophytes once considered pathogenic only in plants, have emerged as serious pathogens in neutropenic patients with malignancies. We describe two patients, one with acute myelogenous leukemia and the other with metastatic breast cancer, in whom disseminated Fusarium solani infection developed. Both patients had neutropenia and fever when generalized, tender, erythematous papules developed; most of the papules had black necrotic centers. Despite aggressive therapy with antifungal agents and granulocyte-macrophage colony-stimulating factor, both patients died within 1 month. Disseminated Fusarium infection can be a life-threatening condition in which skin lesions are frequently the initial sign. Early recognition and hematopoietic recovery offer the best chance for survival.

Fusarium moniliforme was isolated from a pustular lesion on the hand of an otherwise healthy male. Branching hyphae were seen in pus stained by the periodic acid-Schiff method. Pustular lesions containing branching hyphae were produced in mice after subcutaneous injection of microconidia. The experimental infection in mice and the naturally occurring lesion in man healed without treatment in 1 to 2 weeks. Although production of catenulate microconida was abundant on several common laboratory media, the characteristic macroconidia of F. moniliforme were produced only on barley-pea-rice straw agar.

Moulds and arthroconidial yeasts are potential life-threatening agents of fungemia in immunocompromised patients. Fast and accurate identification (ID) of these pathogens hastens initiation of targeted antifungal therapy, thereby improving the patients' prognosis. We describe a new strategy that enabled the identification of moulds and arthroconidial yeasts directly from positive blood cultures by MALDI-TOF mass spectrometry (MS). Positive blood cultures (BCs) with Gram staining showing hyphae and/or arthroconidia were prospectively selected and submitted to an in-house protein extraction protocol. Mass spectra were obtained by Vitek MS system, and identifications were carried out with in the research use only (RUO) mode with an extended database (SARAMIS [v.4.12] plus in-house database). Fusarium solani, Fusarium verticillioides, Exophiala dermatitidis, Saprochaete clavata, and Trichosporon asahii had correct species ID by MALDI-TOF MS analysis of positive BCs. All cases were related to critically ill patients with high mortality fungemia and direct ID from positive BCs was helpful for rapid administration of targeted antifungal therapy.

Neutropenia-related fungal infections can be life-threatening despite antifungal therapy. We evaluated the role of recombinant granulocyte colony-stimulating factor (rG-CSF)-elicited white blood cell (WBC) transfusions in patients with neutropenia-related fungal infections. Adult patients with hematologic malignancies, absolute neutrophil counts (ANC) <500/microl and fungal infections refractory to amphotericin B, received daily transfusions of rG-CSF-elicited and irradiated WBC transfusions from related donors. Donors received 5 microg/kg/day of rG-CSF subcutaneously. Donors achieved a mean ANC of 29.4 x 10(3) per microliter. The mean yield of neutrophils per transfusion was 41 x 10(9) (range, 10-116). Fifteen patients received a median of eight transfusions (range, 3-16). Fourteen patients had received rG-CSF for a median of 12 days. The median ANC baseline was 20/microl. Eleven patients had favorable responses and eight of them remained free of infection 3 weeks after therapy. Favorable responses occurred among patients with better Zubrod performance status (median, 3 vs 4) and shorter duration of both profound neutropenia (median, 15 vs 25 days) and active infection (median, 8 vs 17 days). The mean 1- and 24-h post-transfusion ANCs were 594/microl (range, 98-1472/microl) and 396/microl (range, 50-1475/microl), respectively. Adverse reactions were observed in nine of 35 donors and in the recipients of six of 130 transfusions. rG-CSF-elicited WBC transfusions may be a safe and promising approach for treating neutropenia-related fungal infections.

Fusarium spp. causes infections mostly in patients with prolonged neutropenia. We describe the case of a disseminated Fusarium solani infection in a patient with acute myeloid leukemia which never reached complete remission during its clinical course. The patient had profound neutropenia and developed skin nodules and pneumonia in spite of posaconazole prophylaxis. F. solani was isolated from blood and skin biopsy, being identified from its morphology and by molecular methods. By broth dilution method, the strain was resistant to azoles, including voriconazole and posaconazole, and to echinocandins. MIC to amphotericin B was 4 mg/L. The patient initially seemed to benefit from therapy with voriconazole and amphotericin B, but, neutropenia perduring, his clinical condition deteriorated with fatal outcome. All efforts should be made to determine the correct diagnosis as soon as possible in a neutropenic patient and to treat this infection in a timely way, assuming pathogen susceptibility while tests of antimicrobial susceptibility are pending. A review of the most recent literature on invasive fungal infections is reported.

We report on a case of mixed infection caused by two species of Fusarium in a human immunodeficiency virus-positive patient with lymphoma who was neutropenic due to chemotherapy. The patient showed the typical signs of a disseminated fusarial infection, with Fusarium solani isolated from skin lesions and F. verticillioides isolated from blood. The report discusses how difficult it is to make an accurate diagnosis when an immunosuppressed patient is infected with more than one fungal species, especially when the species are morphologically very similar.

One patient was diagnosed as hyalohyphomycosis by history,medical examnation,pathology and fungal culture.The pathogen was finally identified as Fusarium solani.The patient showed significant improvement after 3-month treatment with itraconazole and part-leision resection.

Fusariosis is due to inhalation or direct contact with conidia. Clinical presentation depends on host's immunity and can be localized, focally invasive or disseminated. Given the severity of this infection and the possibility for the dermatologist to make an early diagnosis, we report six cases of patients with hematologic malignancies, who developed febrile neutropenia an skin lesions suggestive of cutaneous fusariosis. All patients had skin cultures showing growth of Fusarium solani complex, and they received amphotericin B and voriconazole. As this infection can quickly lead to death, dermatologists play a crucial role in diagnosing this disease.

Identification of fungi in tissue sections can be difficult. In particular, species of Aspergillus, Fusarium, and Pseudallescheria all appear as septate, branched hyphae. However, their differentiation can have significant clinical implications, as the latter two groups are often resistant to commonly used antifungal agents. In situ hybridization may assist in rapidly distinguishing these organisms in the absence of available culture. Oligonucleotide DNA probes were directed against the 5S, 18S, or 28S rRNA sequences of three groups of fungi with a high degree of specificity for each. Probes were tested on 26 formalin-fixed, paraffin-embedded tissue specimens, each with culture-proven involvement by one of these organisms: Fusarium species, n = 12; Pseudallescheria boydii, n = 5; Aspergillus species, n = 9 ( probe set validated in an earlier study). Accuracy of both ISH and morphology was compared with culture. Morphologic examination (GMS and PAS) showed a greater sensitivity in detecting fungi (100%) as compared with in situ hybridization (84.6%). When detected, however, DNA probes allowed definitive identification of organisms. While there was no ability to distinguish between the three groups of organisms by morphologic features, ISH probes showed 100% positive predictive value (PPV, 19/19 organisms identified correctly). No cross-reactivity was observed when the probes were tested against other genera (100% specificity). Furthermore, the use of ISH allowed the detection of mixed fungal infections involving multiple organism types in two cases, demonstrating another advantage over morphology. In situ hybridization, directed against rRNA sequences, provides a rapid and accurate technique for distinguishing commonly encountered, nonpigmented filamentous fungi in histologic sections. While less sensitive than morphology, ISH is highly accurate and may help to distinguish between organisms that have similar or identical morphologic features by light microscopy.

Advances in molecular typing of fusariosis would facilitate the study of its epidemiology. We tested 26 such isolates by the commercially available Diversi Lab System. The system utilizes automated repetitive sequence-based PCR (rep-PCR) and web-based data analyses. rep-PCR dendrogram cluster analysis showed agreement with species sequence identification (elongation factor 1 alpha gene). Additionally, subtype differences within the same species were noted.

Objective To study Fusarium solani infection as a complication in patients after allogeneic hemotopoietic stem cell transplantation and to discuss the diagnosis and appropriate therapy.Methods Symptoms, physical examination, laboratory tests, computed tom

BACKGROUND: Invasive Fusarium infection is relatively refractory to available antifungal agents. Invasive fusariosis (IF) occurs almost exclusively in the setting of profound neutropenia and/or systemic corticosteroid use. Treatment guidelines for IF are not well established, including the role of granulocyte transfusions (GTs) to counter neutropenia. STUDY DESIGN AND METHODS: We conducted a systematic review, identifying IF cases where GTs were used as adjunctive therapy to antifungal agents and also report a single-center case series detailing our experience (1996-2012) of all IF cases treated with antifungal agents and GTs. In the systematic review cases, GTs were predominantly collected from nonstimulated donors whereas, in the case series, they were universally derived from dexamethasone- and granulocyte-colony-stimulating factor-stimulated donors. RESULTS: Twenty-three patients met inclusion criteria for the systematic review and 11 for the case series. Response rates after GTs were 30 and 91% in the review and case series, respectively. Survival to hospital discharge remained low at 30 and 45%, respectively. Ten patients in the systematic review and three in the case series failed to achieve hematopoietic recovery and none of these survived. In the case series, donor-stimulated GTs generated mean

Fusarium is a filamentous opportunistic pathogenic fungus responsible for superficial as well as invasive infection in immunocompromized hosts. Net state of immunosuppression and cytomegalovirus (CMV) infection appear to predispose to this disease which is life-threatening when disseminated. Though infections with Fusarium have been widely described in hematological malignancies and hematopoietic stem cell transplant cases, they have been reported to be rare in solid organ transplant recipients, are often localized and carry a favorable prognosis. We here describe a rare case of subcutaneous non-invasive infection with Fusarium in a renal allograft recipient two and half years after transplantation. Patient had a previous history of CMV infection along with multiple other recurrent co-infections. Diagnosis was based on culture of tissue specimens yielding Fusarium species. The infection had a protracted course with persistence of lesions after treatment with voriconazole alone, requiring a combination of complete surgical excision and therapy with the anti-fungal drug.

Fusarium oxysporum was isolated from a large foot ulcer in an otherwise healthy 69-year-old man. Although tissue invasion could not be proven histologically, systemic antifungal treatment was administered with satisfactory response. Fusarium species are common soil-inhabiting organisms and plant pathogens. In humans, Fusarium is considered an opportunistic agent in skin ulcers, interdigital spaces, and burned skin, but can also cause mycotic keratitis, onychomycosis, and rarely deep-seated or disseminated infections, especially in an immunocompromised host. The distinction between skin infection and saprophytic growth, as well as optimal treatment regimens for the two types of infection, have not been clearly defined. We describe a case of leg ulcers caused by Fusarium oxysporum in a 69-year-old man treated successfully with oral ketoconazole.

Fusarium spp. are usually considered opportunistic fungi in humans. A case of Fusarium solani abscess formation of the foot in an immunocompetent patient in whom recurrence occurred even after intravenous amphotericin B treatment is presented here.

Nontraditional human pathogenic fungi, including Fusarium, Paecilomyces, and Acremonium species, have been increasingly documented as agents of infection in immunocompromised patients and, occasionally, in normal hosts. Although definitive identification of these fungi requires culture, they often can be identified provisionally in tissue sections by a combination of histologic features, including hyaline septate hyphae and characteristic reproductive structures known as phialides and phialoconidia. These morphologic characteristics, although familiar to mycologists, are easily overlooked by histopathologists; as a result, Fusarium species and Paecilomyces lilacinus are frequently misidentified in tissue sections as Aspergillus or Candida species. We identified 19 culture-proved cases of infection with species of Fusarium, Paecilomyces, or Acremonium; retrospectively reviewed histologic specimens stained by routine hematoxylin and eosin, Gomori methenamine silver, and/or periodic acid-Schiff stains; and delineated morphologic criteria that will help pathologists make a preliminary identification of these fungi by histopathology. Adventitious sporulation was found in 9 of 9 infections caused by Paecilomyces species, 7 of 10 infections caused by Fusarium species, and in the single case of infection caused by Acremonium strictum. Histologic recognition of these morphologies may help clinicians select appropriate initial antifungal treatment and manage the infection.

Systemic fungal infections with Fusarium occur predominantly in immunocompromised patients and are usually fatal. We report a patient with acute lymphocytic leukemia and fusariosis involving the skin and lungs. This patient underwent antifungal chemotherapy and bilateral pulmonary resections. She subsequently had successful bone marrow transplantation. The results of this treatment suggest that this aggressive management of pulmonary fusariosis offers the best chance of survival.

Fusarium species may cause localised skin infections in immunocompetent individuals. At least half of these infections are preceded by skin breakdown. The lesions are characterised by slow progression and good response to therapy. Here we present a 60-year-old non-diabetic man with stasis ulcers showing Fusarium oxysporum growth in culture of both pus swabs and skin biopsy specimens. The patient was confined to wheelchair because of recurrent sacral chordoma of 15 years duration, which was not under treatment for the last 3 years. Leg ulcers were resistant to antifungal therapy, and healed rapidly after improving of stasis with local and systemic measures.

We describe a 6-year-old boy with a granulomatous lesion on the upper aspect of his left arm. Fusarium solani infection was confirmed by biopsy studies and cultures. The biopsy specimen showed an unusually extensive dermal invasion with fungal hyphae. This is an uncommon clinical presentation for deep cutaneous infection caused by F solani in a healthy child. Local heat therapy with a chemical pocket warmer led to dramatic healing of the lesion.

A case of cutaneous hyalohyphomycosis, due to Fusarium oxysporum, in a 40 years old man is presented. The patient came from Paraguay where he worked in a tropical rural area. His disease had begun 2 months before his admission as a skin ulcer located in the left leg. Clinical characteristics, diagnosis methods, differential diagnosis with other ulcers of the legs in tropical areas as well as therapeutic measures are discussed in this presentation.

There are several taxonomic systems available for identifying Fusarium species. The philosophy used in each taxonomic system is discussed as well as problems encountered in working with Fusarium species in culture. Fusarium species are toxigenic, and the mycotoxins produced by these organisms are often associated with animal and human diseases. The implications for the association of the carcinogens, fumonisins, produced by Fusarium moniliforme and other Fusarium species with human diseases are discussed. Foreign-body-associated fusarial infection such as keratitis in contact lens wearers, onychomycosis, skin infections, and disseminated multiorgan infections are discussed. Disseminated fusarial hyalohyphomycosis has emerged as a significant, usually fatal infection in the immunocompromised host. Successful outcome is determined by the degree of immunosuppression, the extent of the infection, and the presence of a removable focus such as an indwelling central venous catheter. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy, probably with one of the newer antifungal agents. Perhaps the use of such agents or the use of colony-stimulating factors may improve the outcome of this devastating infection. However, until new approaches for treatment develop, effective preventive measures are urgently needed.

Fusarium species cause a broad spectrum of infections in humans, including superficial, locally invasive, and disseminated infections. The clinical form of fusariosis depends largely on the immune status of the host and the portal of entry, with superficial and localized disease occurring mostly in immunocompetent patients and invasive and disseminated disease affecting immunocompromised patients. Risk factors for severe fusariosis include prolonged neutropenia and T-cell immunodeficiency, especially in hematopoietic stem cell transplant recipients with severe graft-versus-host disease. The most frequent presentation of disseminated fusariosis is a combination of characteristic cutaneous lesions and positive blood cultures, with or without lung or sinus involvement. The prognosis is poor and is determined largely by degree of immunosuppression and extent of infection, with virtually a 100% death rate among persistently neutropenic patients with disseminated disease. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy. Treatment options include the lipid formulations of amphotericin B, voriconazole, and posaconazole. Prevention of fusarial infection among high-risk patients should be considered.

Cross-reactivity of Fusarium species with serum galactomannan antigen (GMI) test has been observed. We sought to evaluate if GMI could help to early diagnose invasive fusariosis and to monitor treatment response. We reviewed the records of all patients with invasive fusariosis between 2008 and 2012 in three Brazilian hospitals. We selected patients who had at least 1 GMI test within 2 days before or after the date of the first clinical manifestation of fusariosis, and analyzed the temporal relationship between the first positive GMI test and the date of the diagnosis of invasive fusariosis, and the kinetics of GMI in relation to patients' response to treatment. We also selected 18 controls to determine the sensitivity and specificity of the test. Among 18 patients, 15 (83%) had at least one positive GMI (median 4, range 1-15). The sensitivity and specificity of was 83% and 67%, respectively. GMI was positive before the diagnosis of invasive fusariosis in 11 of the 15 cases (73%), at a median of 10 days (range 3-39), and after the diagnosis in 4 cases. GMI became negative in 8 of the 15 patients; 3 of these 8 patients (37.5%) were alive 90 days after the diagnosis of fusariosis compared with 2 of 7 (29%) who did not normalize GMI (p = 1.0). GMI is frequently positive in invasive fusariosis, and becomes positive before diagnosis in most patients. These findings may have important implications for the choice of antifungal therapy in settings with high prevalence of invasive fusariosis.

The Glucatell (1-->3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.

Members of the species-rich Fusarium solani species complex (FSSC) are responsible for approximately two-thirds all fusarioses of humans and other animals. In addition, many economically important phytopathogenic species are nested within this complex. Due to their increasing clinical relevance and because most of the human pathogenic and plant pathogenic FSSC lack Latin binomials, we have extended the multilocus haplotype nomenclatural system introduced in a previous study (D. C. Chang, G. B. Grant, K. O'Donnell, K. A. Wannemuehler, J. Noble-Wang, C. Y. Rao, L. M. Jacobson, C. S. Crowell, R. S. Sneed, F. M. T. Lewis, J. K. Schaffzin, M. A. Kainer, C. A. Genese, E. C. Alfonso, D. B. Jones, A. Srinivasan, S. K. Fridkin, and B. J. Park, JAMA 296:953-963, 2006) to all 34 species within the medically important FSSC clade 3 to facilitate global epidemiological studies. The typing scheme is based on polymorphisms in portions of the following three genes: the internal transcribed spacer region and domains D1 plus D2 of the nuclear large-subunit rRNA, the translation elongation factor 1 alpha gene (EF-1alpha), and the second largest subunit of RNA polymerase II gene (RPB2). Of the 251 isolates subjected to multilocus DNA sequence typing, 191 sequence types were differentiated, and these were distributed among three strongly supported clades designated 1, 2, and 3. All of the mycosis-associated isolates were restricted to FSSC clade 3, as previously reported (N. Zhang, K. O'Donnell, D. A. Sutton, F. A Nalim, R. C. Summerbell, A. A. Padhye, and D. M. Geiser, J. Clin. Microbiol. 44:2186-2190, 2006), and these represent at least 20 phylogenetically distinct species. Analyses of the combined DNA sequence data by use of two separate phylogenetic methods yielded the most robust hypothesis of evolutionary relationships and genetic diversity within the FSSC to date. The in vitro activities of 10 antifungals tested against 19 isolates representing 18 species that span the breadth of the FSSC phylogeny show that members of this complex are broadly resistant to these drugs.

Because less than one-third of clinically relevant fusaria can be accurately identified to species level using phenotypic data (i.e., morphological species recognition), we constructed a three-locus DNA sequence database to facilitate molecular identification of the 69 Fusarium species associated with human or animal mycoses encountered in clinical microbiology laboratories. The database comprises partial sequences from three nuclear genes: translation elongation factor 1alpha (EF-1alpha), the largest subunit of RNA polymerase (RPB1), and the second largest subunit of RNA polymerase (RPB2). These three gene fragments can be amplified by PCR and sequenced using primers that are conserved across the phylogenetic breadth of Fusarium. Phylogenetic analyses of the combined data set reveal that, with the exception of two monotypic lineages, all clinically relevant fusaria are nested in one of eight variously sized and strongly supported species complexes. The monophyletic lineages have been named informally to facilitate communication of an isolate's clade membership and genetic diversity. To identify isolates to the species included within the database, partial DNA sequence data from one or more of the three genes can be used as a BLAST query against the database which is Web accessible at FUSARIUM-ID (http://isolate.fusariumdb.org) and the Centraalbureau voor Schimmelcultures (CBS-KNAW) Fungal Biodiversity Center (http://www.cbs.knaw.nl/fusarium). Alternatively, isolates can be identified via phylogenetic analysis by adding sequences of unknowns to the DNA sequence alignment, which can be downloaded from the two aforementioned websites. The utility of this database should increase significantly as members of the clinical microbiology community deposit in internationally accessible culture collections (e.g., CBS-KNAW or the Fusarium Research Center) cultures of novel mycosis-associated fusaria, along with associated, corrected sequence chromatograms and data, so that the sequence results can be verified and isolates are made available for future study.

BACKGROUND: Measurement of (1-->3)-beta-D-Glucan (BG) has emerged as an adjunct diagnostic strategy for invasive fungal infections (IFI). METHODS: Subjects at 6 clinical sites in the United States were enrolled as either fungal infection-negative subjects (n = 170) or subjects with proven or probable IFI according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria (n = 163). A central laboratory and 4 sites performed assays. A single sample was obtained per patient and was evaluated using an assay to detect serum BG derived from fungal cell walls (range, 0 to > 7000 pg/mL). RESULTS: At a cutoff of 60 pg/mL, the sensitivity and specificity of the assay were 69.9% and 87.1%, respectively, with a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 75.1%. At a cutoff value of 80 pg/mL, the sensitivity and specificity were 64.4% and 92.4%, respectively, with a PPV of 89% and an NPV of 73%. Of the 107 patients with proven candidiasis, 81.3% had positive results at a cutoff value of 60 pg/mL, and 77.6% had positive results at a cutoff value of 80 pg/mL. Of the 10 patients with aspergillosis, 80% had positive results at cutoff values of 60 and 80 pg/mL. The 3 subjects diagnosed with Fusarium species had positive results at a cutoff value of 60 pg/mL. Patients infected with Mucor or Rhizopus species (both of which lack BG) had negative results at both cutoff values, and of the 12 patients with Cryptococcus infection, 3 had positive results at a cutoff value of 60 pg/mL, and 2 had positive results at a cutoff value of 80 pg/mL. Of the subjects with proven positive results who were receiving antifungal therapy (n = 118), 72.9% had results positive for BG at a cutoff value of 60 pg/mL, and 69.5% had results positive for BG at a cutoff value of 80 pg/mL. The interlaboratory sample test r2 was 0.93. CONCLUSION: Reproducible assay results with high specificity and high PPV in a multicenter setting demonstrate that use of an assay to detect serum BG derived from fungal cell walls is a useful diagnostic adjunct for IFI.

After allogeneic stem cell transplantation, a 49-year-old man developed fever and inflammation at the site of a plant puncture on a finger. A hyalohyphomycete was recovered by incubating the plant spine fragment following surgery. Amplification of the internal transcribed spacer region and 5.8S rRNA, beta-tubulin, and translation elongation factor coding genes identified Fusarium proliferatum, which was confirmed later by culture.

Despite appropriate antimicrobial and antifungal therapy (amphotericin B), a disseminated infection with Fusarium oxysporum in a 75-year-old immunocompromised patient (acute myeloid leukaemia, minimal leucocyte count of 0.5 giga l-1) led rapidly to death. A similarly fatal course of an F. oxysporum infection has been reported in several cases. Fusarium oxysporum could be isolated shortly before death from blood cultures and from a swab taken from skin efflorescences. An autopsy revealed histopathologically typical fungal infiltrates in the mucosa of the pharynx, epiglottis, trachea, and oesophagus and in the parenchyma of the spleen, the lung and both kidneys. Because of the high risk of a fatal outcome of this infection, the clinician should aim at maximum diagnostic enforcement. We propose both analysis of blood cultures and immediate skin biopsy--with PAS-staining--of suspicious dermal efflorescences for microscopic examination. The treatment of choice is discussed controversially but a beneficial effect has been reported from granulocyte transfusion, subcutaneous administration of GM-CSF and concomitant treatment with amphotericin B.

A 67-year-old female presented with a 20-year-old lesion involving the right ear and preauricular area mimicking tuberculous lupus. Fusarium oxysporum infection was confirmed by biopsy studies and cultures. The biopsy specimen showed an unusually extensive dermal invasion with fungal hyphae. This is an uncommon clinical presentation for Fusarium infection in a healthy patient. When referred to us, the patient had received antifungal therapy with itraconazole without any benefit. Improvement was obtained with fluconazole therapy. The spectrum of cutaneous involvement related to Fusarium spp. includes toxic reactions, colonization, superficial indolent infection, deep cutaneous or subcutaneous infections and disseminated infection.

Fusarium spp. are emergent opportunistic moulds capable of producing life-threatening diseases, usually in immunocompromised hosts. When they infect immunocompetent patients, they usually cause localized diseases. We describe here a case of cutaneous fusariosis in a patient with a medical history of diabetes mellitus and non-Hodgkin's lymphoma who presented with two painful lesions on her left leg. The diagnosis was made on the basis of histopathological findings and skin biopsy culture. The lesions resolved after treatment with oral itraconazole. Cutaneous fusariosis manifests clinically as lesions that can be grouped into a few clinical patterns, and should always be considered in the differential diagnosis of necrotic cutaneous lesions.

We report a case of Fusarium oxysporum fungemia that was related to the presence of a central venous catheter and was confirmed by quantitative cultures and scanning electron microscopy of the catheter hub, subcutaneous segment and cuff, and tip. Despite progressive neutropenia, the infection responded to antifungal therapy within 1 day after the catheter was removed. The removal of the catheter could have contributed to the patient's early favorable response.

There are approximately 14 million persons with diabetes in the United States. These patients must cope with the serious complications of this disease, including neuropathy and impaired circulation (leading to the

Fusarium is a ubiquitous hyalohyphomycete isolated from food, widespread in the environment (plants, soil) and present at all latitudes. Fusarium oxysporum and Fusarium solani are the most frequent pathogenic species, followed by F. moniliforme and F. chlamydosporum. Infections due to this mold may be disseminated or localized. Localized forms include cutaneous and subcutaneous infection, onychomycosis, endophtalmitis, otitis, sinusitis, arthritis, osteomyelitis, and brain abscess. Disseminated forms are those in which two or more noncontiguous sites may be involved. These latter are observed in patients with severe neutropenia. Wounds, digital ulcers, onychomycosis, and paronychia are the typical cutaneous portal of entry. We report a case of primary localized cutaneous infection due to Fusarium in a 29-year-old woman presenting with a nodular lesion, partially ulcerated, asymptomatic on the first finger of the left hand, appeared 4 months earlier. Histological examination showed spongiosis and acanthosis in the stratum corneum, ulceration and inflammation with prevalently mononucleate cells and septate and branched fungal structures in the epidermis and in dermis. The fungus was identified as Fusarium oxysporum by culture of biopsy fragments on Sabouraud dextrose agar with chloramphenicol. The culture was deposited in the culture collection of the mycology section of IHEM, Brussels (IHEM21984 col no. 125). The patient had normal immune status and was successfully treated with surgical excision. Recovery was confirmed at follow-up 8 months later.

In a retrospective multicenter study, 102 formalin-fixed paraffin-embedded (FFPE) tissue specimens with histopathology results were tested. Two 4- to 5-mum FFPE tissue sections from each specimen were digested with proteinase K, followed by automated nucleic acid extraction. Multiple real-time quantitative PCR (qPCR) assays targeting the internal transcribed spacer 2 (ITS2) region of ribosomal DNA, using fluorescently labeled primers, was performed to identify clinically important genera and species of Aspergillus, Fusarium, Scedosporium, and the Mucormycetes The molecular identification was correlated with results from histological examination. One of the main findings of our study was the high sensitivity of the automated DNA extraction method, which was estimated to be 94%. The qPCR procedure that was evaluated identified a range of fungal genera/species, including Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus niger, Fusarium oxysporum, Fusarium solani, Scedosporium apiospermum, Rhizopus oryzae, Rhizopus microsporus, Mucor spp., and Syncephalastrum Fusarium oxysporum and F. solani DNA was amplified from five specimens from patients initially diagnosed by histopathology as having aspergillosis. Aspergillus flavus, S. apiospermum, and Syncephalastrum were detected from histopathological mucormycosis samples. In addition, examination of four samples from patients suspected of having concomitant aspergillosis and mucormycosis infections resulted in the identification of two A. flavus isolates, one Mucor isolate, and only one sample having both R. oryzae and A. flavus Our results indicate that histopathological features of molds may be easily confused in tissue sections. The qPCR assay used in this study is a reliable tool for the rapid and accurate identification of fungal pathogens to the genus and species levels directly from FFPE tissues.

We describe a case of soft tissue infection caused by Fusarium species in a heart-liver transplant recipient, and review the cases of fusarial infection reported among solid-organ transplant (SOT) recipients. Unlike fusarial infection in patients with hematologic malignancies or bone marrow transplants, fusarial infection in SOT recipients tends to be localized, occurs later in the posttransplantation period, and has a better outcome. Surgical resection, when possible, and prolonged treatment with amphotericin provide the most effective form of therapy.

Invasive fungal infection (IFI) is an important cause of mortality in immunocompromised children, particularly after hematopoietic stem cell transplantation. We describe 5 cases of Fusarium IFI in immunocompromised children seen at our institution over a 15-year period. A summary of all published pediatric cases of invasive Fusarium infection is presented. A focus on antifungal management challenges in these patients will be discussed.

Although mycoses are among the most common diseases worldwide, infections with Fusarium spp. occur only rarely. Mostly patients suffering from underlying immune deficiency are infected with this mould, resulting in a considerably decreasing prognosis. In immunocompromised patients, cutaneous manifestations are more often associated with Fusarium sp. than with Candida sp. or Aspergillus sp. We describe one patient with acute lymphoblastic leukaemia, who was first treated with chemotherapy after GMALL protocol 07/03. After relapse, the patient was successfully transplanted in second remission with a human leukocyte antigen (HLA)-matched unrelated peripheral blood stem cell graft. Ten months later, the patient died from respiratory insufficiency and recurrence of leukaemia. Previously, Aspergillus antigen was detected in blood. In the latter course, disseminated papules appeared. One of these was examined histologically and mycologically. Conventional cultural diagnostics led to the diagnosis of a fusariosis, further supported by internal transcribed spacer (ITS) sequencing and matrix assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF) mass spectrometry, both determining the isolated strain as Fusarium proliferatum, which is a very infrequent pathogen within this genus. Our investigations underline the potential of MALDI-TOF MS based identification of Fusarium species as an innovative, time and cost efficient alternative to ITS sequencing.

A 65-year-old man presented with an irregular ulcer with a black eschar on his forehead associated with severe headache. A subcutaneous nodule with a necrotic center was present on the left knee. The diagnosis of Fusarium infection was made and confirmed by biopsy and culture. The patient had a history of bronchial asthma for which he was on inhalational steroids for 5 years. It is unclear if this treatment was related to the disseminated Fusarium infection. The patient received oral itraconazole for 3 months with good improvement but met with an unexpected sudden death.

Objective To explore the clinical and laboratory features of leg ulcer caused by Fusarium moniliforme.Methods Characteristics of Fusarium moniliforme was observed by microscopy and fungal culture.Pathological examination was performed for diagnosis.Results White and cottony mould colony grew on PDA agar at 25℃ with sickle-like macroconidia,concatenate and capitulum-like microconidium under microscope and scanning electron microscope.The fungi was identified as F.moniliforme with the ability growing at 25℃ and 37℃ on Sabrous agar.Chroic granuloma was found,but no fungal components were observed by PAS or silver staining.The lesions were cured after voriconazole and terbinafine treatment combined with debridement and skingrafting.Conclusions A case of leg ulcer caused by Fusarium moniliforme was diagnosed and cured by combination therapy of voriconazole with surgery.

The use of granulocyte transfusions during amphotericin B treatment of invasive fungal infections in granulocytopenic patients is controversial because of concern about pulmonary complications from leukostasis. Moreover, the administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with active infections has been questioned because of reports that this cytokine inhibits neutrophil migration into areas of inflammation. We report a case in which the combined use of amphotericin B, granulocyte transfusions, and GM-CSF was safe and life-saving in a pancytopenic patient with disseminated fusarium infection. Histologic evidence of the migration of neutrophils into an area of active infection was found.

Foot infections are common and serious complications of diabetic patients. We report the case of a 68-year-old patient with a diabetic foot infection that developed into a gangrenous necrosis. Fusarium spp. was isolated on two successive occasions with no other associated microorganisms. Histopathology demonstrated invasion of the fungus into the tisssue. These findings suggested an infection rather than colonization. A detailed morphological study showed that the isolate was Fusarium acutatum, which was confirmed by rDNA sequencing. This fungus is found only in Asia and has not been previously reported as a human pathogen.

Eumycetoma is a mycotic disease caused by saprophytic soil fungi that are usually inoculated through minor injuries. A case of mycetoma in a Brazilian farmer aged71 years is reported. This patient presented erythema and edema on the dorsal surface of the left hand with multiple crusted and cicatricial lesions. No macroscopic grains were observed. The histopathological findings showed grains consisted of numerous hyphae which stained well with Gomori-Grocott method. This material obtained by cutaneous biopsy was submitted to culture on Sabouraud’s medium and the colonies were identified as Fusarium solani. The radiological studies revealed bone osteolytic lesions and the ultrasound showed pseudocysts and fistulae at the site of this infection. The patient was treated with oral ketoconazole with a good clinical response.

Nine of 11 hematological patients with disseminated/deep-seated Fusarium infection tested at least twice for Aspergillus galactomannan (GM) had repeated positive results in the absence of Aspergillus isolation in culture. The centrifuged supernatants of 12 Fusarium isolates were tested by a GM enzyme-linked immunosorbent assay (EIA). All the isolates produced positive reactions when tested undiluted. These results show cross-reactivity of Fusarium spp. with Aspergillus GM that may constitute a drawback with respect to the specificity of the Platelia EIA.

The rates of infection with Fusarium molds are increasing, and a diverse number of Fusarium spp. belonging to different species complexes can cause infection. Conventional species identification in the clinical laboratory is time-consuming and prone to errors. We therefore evaluated whether matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a useful alternative. The 289 Fusarium strains from the Belgian Coordinated Collections of Microorganisms (BCCM)/Institute of Hygiene and Epidemiology Mycology (IHEM) culture collection with validated sequence-based identities and comprising 40 species were used in this study. An identification strategy was developed, applying a standardized MALDI-TOF MS assay and an in-house reference spectrum database. In vitro antifungal testing was performed to assess important differences in susceptibility between clinically relevant species/species complexes. We observed that no incorrect species complex identifications were made by MALDI-TOF MS, and 82.8% of the identifications were correct to the species level. This success rate was increased to 91% by lowering the cutoff for identification. Although the identification of the correct species complex member was not always guaranteed, antifungal susceptibility testing showed that discriminating between Fusarium species complexes can be important for treatment but is not necessarily required between members of a species complex. With this perspective, some Fusarium species complexes with closely related members can be considered as a whole, increasing the success rate of correct identifications to 97%. The application of our user-friendly MALDI-TOF MS identification approach resulted in a dramatic improvement in both time and accuracy compared to identification with the conventional method. A proof of principle of our MALDI-TOF MS approach in the clinical setting using recently isolated Fusarium strains demonstrated its validity.

A case of untreated fusarial onychomycosis leading to serious consequences is reported. Fusarium solani is a widespread fungus and an occasional human pathogen. It usually invades rapidly in immunocompromised hosts, and often results in a poor outcome despite treatment. We report a woman with diabetes mellitus who had untreated fusarial infection of the nails, which developed into subcutaneous fusariosis, superinfected by bacteria, and then evolved into osteomyelitis that subsequently resulted in septic shock. Early management of mycotic nails in immunocompromised hosts is crucial to prevent life-threatening disease.

We report a case of Fusarium solani mycetoma of the foot that could not be diagnosed by culture, but was correctly identified after amplification and sequence analysis of fungal internal transcribed spacers 1 and 2 and 5.8S ribosomal DNA regions.

目的 报道1例茄病镰刀菌引起的足部透明丝孢霉病。方法 询问病史及体检,取足部的皮损行皮肤病理检查、真菌培养及致病菌的形态学观察、鉴定。结果 致病菌为茄病镰刀菌,给予局部病灶切除及伊曲康唑治疗,随访3个月,病灶明显缩小。结论 本病例证实为茄病镰刀菌引起的足部透明丝孢霉病,经口服伊曲康唑及局部病灶切除治疗,疗效明显。

目的 提高对免疫低下患者茄病镰刀菌感染的认识,探讨治疗方案.方法 报道1例急性髓性白血病异基因造血干细胞移植后合并茄病镰刀菌感染患者的临床表现、治疗经过和转归并进行文献复习.结果 患者男,46岁,于干细胞移植术后出现肺部浸润影及全身多发性皮下包块,组织涂片见大量菌丝及孢子,真菌培养为茄病镰刀菌,行皮下包块切开引流,两性霉素B及伏立康唑抗真菌治疗,恢复后痊愈出院.以"造血干细胞移植"或"异基因造血干细胞移植"或"骨髓移植"+"茄病镰刀菌"为关键词在Medline和中国生物医学文献光盘数据库中进行检索,未发现中文报道,国外文献报道7篇,共8例,其中男5例,女3例,主要临床表现为发热及全身皮肤损害,预后极差,8例中7例死亡,1例治愈.结论 茄病镰刀菌感染是造血干细胞移植后少见的、致死性的并发症,应引起足够重视,对异常皮肤损害或皮下包块应尽快行组织涂片及培养,早期明确诊断并给予足量抗真菌治疗.

目的 探讨串珠镰刀菌致小腿溃疡患者临床及实验室特征。方法 多次取患者溃疡分泌物作直接镜检和真菌培养,观察真菌形态学特征。取皮损组织病理活检。结果 在马铃薯培养基中25℃培养均长出白色棉絮状菌落,显微镜及扫描电镜下见大分生孢子呈镰刀状,小分生孢子链生和假头状着生并存,在沙堡琼脂25℃和37℃均生长良好,经鉴定为串珠镰刀菌。组织病理学显示为慢性炎性肉芽肿改变,PAS及六胺银染色均未见真菌成分。伏立康唑联合特比萘芬治疗有效,整形外科清创植皮后治愈。结论 确诊1例串珠镰刀菌引起的小腿溃疡,伏立康唑联合手术治疗皮肤镰刀菌感染疗效好。