An updated comprehensive systematic review of Cladophialophora bantiana and analysis of epidemiology, clinical characteristics, and outcome of cerebral cases.

Cladophialophora bantiana is a phaeoid fungus that only rarely has been isolated from sources other than the human brain. It has a particular tropism for the central nervous system (CNS). We have integrated and updated large-scale data related to several aspects of C. Bantiana and reviewed all the available reports on its cerebral infections, focusing on their geographical distribution, infection routes, immune status of infected individuals, type and location of infections, clinical manifestations and treatment and outcome, briefly looking over the spectrum of other disease entities associated with C. bantiana, that is, extra-cerebral and animal infections and on the environmental sources of this fungus. Among the agents of phaeohyphomycosis, a term used to describe an infection caused by a dark pigmented fungus, C. bantiana has some significant specific features. A total of 120 case reports were identified with a significantly higher percentage of healthy subjects than immune-debilitated patients (58.3% vs. 41.7%). Infections due to C. bantiana occur worldwide. The main clinical manifestations are brain abscess (97.5%), coinfection of brain tissue and meninges (14.2%) and meningitis alone (2.5%). Among immunocompetent patients, cerebral infection occurred in the absence of pulmonary lesions. The mortality rate is 65.0% regardless of the patient's immune status. The therapeutic options used include surgery or antifungals alone, and the combination of both, in most cases the fatal outcome being rapid after admission. Since the fungus is a true pathogen, laboratory workers should be made aware that BioSafety Level-3 precautions might be necessary.

Microbiota-Gut-Brain Axis: Yeast Species Isolated from Stool Samples of Children with Suspected or Diagnosed Autism Spectrum Disorders and In Vitro Susceptibility Against Nystatin and Fluconazole.

Autism spectrum disorder (ASD) is a general term for a group of complex neurodevelopmental disorders of brain development that limits a person's ability to function normally. Etiology has not been clearly defined up to date. However, gut microbiota and the bidirectional communication between the gastrointestinal tract and brain, the so-called microbiota-gut-brain axis, are hypothesized, which may be involved in the etiology of several mental disorders. Recent reports suggest that Candida, particularly Candida albicans, growth in intestines may cause lower absorption of carbohydrates and minerals and higher toxin levels which are thought to contribute autistic behaviors. The aim of this study was to identify the 3-year deposited yeasts isolated from stool samples of children with diagnosed or suspected ASD and to determine in vitro activity of nystatin and fluconazole against these isolates using Clinical Laboratory Standards Institute M27-A3 guidelines. A 17-year retrospective assessment was also done using our laboratory records. Among the species identified, intrinsically fluconazole-resistant Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly isolated species in 17 years. The species identification and/or antifungal susceptibility tests have to be performed using the strain isolated from stool sample, to select the appropriate antifungal agent, if antimycotic therapy is needed.

A dark strain in the Fusarium solani species complex isolated from primary subcutaneous sporotrichioid lesions associated with traumatic inoculation via a rose bush thorn.

Fusarium species are hyaline hyphomycetes widely distributed in nature and documented agents of both superficial and systemic infections in humans. In this paper, we report a darkly-pigmented and initially non-sporulating isolate in the Fusarium solani species complex (FSSC) causing a post-traumatic sporotrichoid infection in an otherwise healthy, male patient. Sequencing of multiple loci showed that the isolate represented an otherwise unknown lineage, possibly corresponding to a separate species, within the multi-species F. solani complex. In prolonged culture, the non-sporulating isolate produced revertant wild-type subcultures with typical Fusarium conidiation. This suggests that the original dense, dark, non-sporulating isolate was a host-adapted form selected in vivo for characters compatible with human pathogenicity. The production of such forms by Fusarium species is increasingly recognized now that sequencing has allowed the identification of highly atypical isolates. In vitro antifungal susceptibility of the isolate was investigated against seven conventional and two newly approved antifungal agents. The isolate showed in vitro resistance to amphotericin B, but appeared susceptible to itraconazole and terbinafine. A cure was ultimately achieved with combined terbinafine/itraconazole therapy with prolonged itraconazole follow-up therapy.

Epidemiology and outcome of Scedosporium prolificans infection, a review of 162 cases.

Scedosporium prolificans is a truly emerging fungal pathogen. It has only been recognized as a human pathogen for 22 years and has been related with numerous infections in immunocompromised and immunocompetent patients. A search for cases in the literature was performed and a database was constructed. Cases were reviewed in order to analyse the epidemiology and outcome of infection. A total of 162 cases were included. The median age of patients was 45 years (ranging from a few months to 81 years), and 102 (63%) infections were diagnosed in males. Risk factors for scedosporiosis were malignancy, 74/162 (45.7%), cystic fibrosis, 19/172 (11.7%), and solid organ transplantation 14/162 (8.6%). The most common clinical presentations were disseminated infection, 72/162 cases (44.4%), pulmonary mycosis, 47/162 (29%), and bone and joint infections, 17/162 (10.4%). All disseminated infections afflicted patents with underlying diseases, primarily haematological malignancies (57/72 [80%]). Blood cultures were positive in 70% of patients suffering from disseminated mycosis. Neutropenia, fever and cerebral symptoms were independently related to the development of disseminated infection whereas recovery from aplasia was associated with a reduced risk. The overall mortality was 46.9% but mortality rate was 87.5% in patients with disseminated disease. Survival was independently associated with surgical excision and recovery from aplasia. Antifungal treatments were not related to a reduced risk of death. Infections caused by S. prolificans are life threatening in susceptible patients, and can be considered a truly emerging disease. Infections are difficult to treat since it is a multi-resistant species. Multicenter studies are essential with the aim of developing and disseminating appropriate techniques and protocols to treat this mycosis.

Central nervous system infections by members of the Pseudallescheria boydii species complex in healthy and immunocompromised hosts: epidemiology, clinical characteristics and outcome.

Infections caused by members of the Pseudallescheria boydii species complex are currently among the most common mould infections. These fungi show a particular tropism for the central nervous system (CNS). We reviewed all the available reports on CNS infections, focusing on the geographical distribution, infection routes, immunity status of infected individuals, type and location of infections, clinical manifestations, treatment and outcome. A total of 99 case reports were identified, with similar percentage of healthy and immunocompromised patients (44% vs. 56%; P = 0.26). Main clinical types were brain abscess (69%), co-infection of brain tissue and/or spinal cord with meninges (10%) and meningitis (9%). The mortality rate was 74%, regardless of the patient's immune status, or the infection type and/or location. Cerebrospinal fluid culture was revealed as a not very important tool as the percentage of positive samples for P. boydii complex was not different from that of negative ones (67% vs. 33%; P = 0.10). In immunocompetent patients, CNS infection was preceded by near drowning or trauma. In these patients, the infection was characterised by localised involvement and a high fatality rate (76%). In contrast, CNS infection in immunocompromised patients was presented as rapidly progressive disseminated lesions at various degrees of evolution. Major risk factors for CNS infection were the aspiration of polluted water in near-drowning episodes in immunologically intact patients and medical immunosuppression in the remaining patient groups. As the therapeutic options were poor, the treatment was difficult in general and the prognosis was poor.

Acral manifestations of fungal infections.

Fungal infections, which are named according to the body site involved, can affect any skin area, the fingernails, or the toenails. Numerous fungal agents are responsible for both superficial and deep fungal diseases. Dermatophytes and Candida spp are the most common causative organisms on the surface of the hands, feet, and nails of patients with superficial fungal diseases; however, although deep fungal infections of the skin are less common compared with superficial fungal diseases, their incidence is increasing worldwide due to cross-border travel. Most superficial fungal diseases are diagnosed clinically, but sometimes direct microscopic examination with potassium hydroxide and fungal culture may be necessary for diagnosis, especially in patients suspected of having tinea incognito. In cases of superficial fungal infections except for onychomycosis and tinea incognito, topical treatments are usually sufficient and effective, but systemic treatments may be required in recalcitrant cases. Deep fungal diseases may resemble each other clinically; therefore, the organism must be identified with laboratory methods and should be treated for a long period. We review the most important clinical, diagnostic, and therapeutic aspects of fungal diseases. This paper covers fungal problems encountered both in hospitals and in general practice.

A case of central nervous system infection due to Cladophialophora bantiana.

BACKGROUND: Cladophialophora bantiana is a melanised mold with a pronounced tropism for the central nervous system, almost exclusively causing human brain abscesses. CASE REPORT: We describe a case of cerebral infection by this fungus in an otherwise healthy 28-year-old coal-miner. Environmental occurrence, route of entry, and incubation period of this fungus are unknown, but our case is informative in that the first symptoms occurred about eight weeks after known traumatic inoculation. Lesions were compatible with tuberculous granulomas, and the patient initially received antitubercular treatment. Melanised fungal cells were seen in a brain biopsy and abscess materials. Therapy was switched from empirical antitubercular treatment to amphotericin B (0.5mg/kg/d), but was changed to voriconazole 200mg/d, i.v. on the basis of antifungal susceptibility test results. The patient responded clinically, and gradually improved. The isolate was identified by sequencing of the Internal Transcribed Spacer domain of rDNA. CONCLUSIONS: Given the non-specific clinical manifestations of C. bantiana cerebral abscesses, clinicians and laboratory workers should suspect infections caused by C. bantiana, particularly in immunocompromised patients with a trauma history.

First imported coccidioidomycosis in Turkey: A potential health risk for laboratory workers outside endemic areas.

Coccidioidomycosis caused by Coccidioides immitis or Coccidioides posadasii is endemic in arid climate zones in America, travel-related cases have been reported. We report the first documented case of coccidioidomycosis in Turkey, overviewing reported cases in Europe and underlying difficulties of differential diagnosis outside endemic regions. The patient was an otherwise healthy 41-year-old man who travelled endemic areas. Laboratory diagnosis was based on direct microscopy of two subsequent subcutaneous biopsy specimens and culture and confirmed molecularly. Laboratory personnel should become aware that BioSafety Level-3 organisms may become more frequent and widespread.

Susceptibility testing of Cryptococcus diffluens against amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole.

Cryptococcus diffluens is a recently re-established species that shares several phenotypic features with Cryptococcus neoformans. We evaluated the application of the Clinical Laboratory Standards Institute (CLSI, formerly NCCLS) macro- and microbroth dilution methods and the E-test agar diffusion method to determine the in vitro susceptibilities of known strains of C. diffluens against amphotericin B (AMB), flucytosine (5-FC), fluconazole (FLC), itraconazole (ITC) and the novel triazoles, voriconazole (VRC) and posaconazole (PSC). Seven strains were found to be resistant in vitro to AMB (MICs >/=2 microg/ml), five were resistant to 5-FC (MICs of >/=32 microg/ml), four were resistant to FLC (MICs of FLC >/=32 microg/ml) and nine were resistant to ITC (MICs of ITC >1 microg/ml). In contrast, VRC and PSC showed good in vitro activity against C.diffluens strains, even those with elevated MICs to amphotericin B and/or established azoles. Most of the isolates were inhibited by 0.5 microg/ml of both VRC and PSC. A clinical isolate showing phenotypic switching exhibited elevated MICs to both agents, i.e., VRC (>16 microg/ml) and PSC (>8 microg/ml).

Fatal Trichoderma harzianum infection in a leukemic pediatric patient.

We report the repeated isolation for Trichoderma.harzianum, a rare opportunistic pathogen from three sets of each of the following clinical samples; blood serum, skin lesions, sputum and throat of a pediatric ALL patient with neutropenia. The definition of invasive fungal infection requires evidence of the presence of fungal elements in tissue samples, in addition to the isolation of suspected etiologic agent in culture. However, invasive procedures are not always applicable due to several factors, as for example in our case, the poor general status of the individual patient or thrombocytopenia. The present paper also emphasizes the problems encountered in obtaining appropriate samples and diagnosing invasive fungal disease in immunocompromised patient populations, including those with hematological malignancy. Three cases involving T. harzianum, including this one, have been described thus far in the literature. All were fatal and the fungus was resistant to antifungal therapy. A critical review of the other two cases of Trichoderma infections in humans is provided.

Fungal rhinosinusitis: a categorization and definitional schema addressing current controversies.

BACKGROUND: Fungal (rhino-) sinusitis encompasses a wide spectrum of immune and pathological responses, including invasive, chronic, granulomatous, and allergic disease. However, consensus on terminology, pathogenesis, and optimal management is lacking. The International Society for Human and Animal Mycology convened a working group to attempt consensus on terminology and disease classification. DISCUSSION: Key conclusions reached were: rhinosinusitis is preferred to sinusitis; acute invasive fungal rhinosinusitis is preferred to fulminant, or necrotizing and should refer to disease of <4 weeks duration in immunocompromised patients; both chronic invasive rhinosinusitis and granulomatous rhinosinusitis were useful terms encompassing locally invasive disease over at least 3 months duration, with differing pathology and clinical settings; fungal ball of the sinus is preferred to either mycetoma or aspergilloma of the sinuses; localized fungal colonization of nasal or paranasal mucosa should be introduced to refer to localized infection visualized endoscopically; eosinophilic mucin is preferred to allergic mucin; and allergic fungal rhinosinusitis (AFRS), eosinophilic fungal rhinosinusitis, and eosinophilic mucin rhinosinusitis (EMRS) are imprecise and require better definition. In particular, to implicate fungi (as in AFRS and EMRS), hyphae must be visualized in eosinophilic mucin, but this is often not processed or examined carefully enough by histologists, reducing the universality of the disease classification. A schema for subclassifying these entities, including aspirin-exacerbated rhinosinusitis, is proposed allowing an overlap in histopathological features, and with granulomatous, chronic invasive, and other forms of rhinosinusitis. Recommendations for future research avenues were also identified.

Subcutaneous cryptococcosis due to Cryptococcus diffluens in a patient with sporotrichoid lesions case report, features of the case isolate and in vitro antifungal susceptibilities.

Environmental fungi, in particular primary pathogens and Cryptococcus spp. can be responsible for skin lesions mimicking sporotrichosis. In this paper, we report a case of subcutaneous cryptococcosis in an apparently healthy, young male patient due to a non-C. neoformans Cryptococcus species, C. diffluens. The isolate showed in vitro phenotypic switching that may affect virulence and host inflammatory and immune responses, and in vitro resistance to amphotericin B and 5-flucytosin. This species shares several phenotypic traits with C. neoformans, and, therefore, decisive diagnosis should be based on biopsy and culturing results followed by molecular identification.

Cryptococcal parotid involvement: an uncommon localization of Cryptococcus neoformans.

We describe a cryptococcal infection localized in the parotid gland of an otherwise healthy 72-year-old woman. The patient presented with a painful, approximately 4.5 cm diameter mass in the anterior region of her right ear. Her symptoms were mild and uncharacteristic. The patient had previously fallen on her face in her garden, causing the loss and breakage of her dentures. Since the soil of the garden contained chicken droppings, it is quite likely that the oral prothesis became contaminated on contacting the soil. The fungus probably entered the parotid gland through the traumatization of the posterior lateral wall of her oral cavity by her broken denture. Numerous intra- and extracellular cryptococcal yeast cells were observed in both histopathological and mycological slide preparations. The yeastlike fungus was recovered in cultures inoculated with tissue collected through three biopsies of her parotid region. The isolates were identified as Cryptococcus neoformans by classical mycology methods and found to be susceptible, in vitro, to fluconazole, amphotericin B and flucytosine. Fluconazole treatment (400 mg/d, for 6 months) was started and the patients facial swelling resolved and the pain significantly reduced within 5 weeks of the initiation of treatment. While fungal infection of the parotid gland have been reported, to our knowledge, this is the first description of a non-disseminated primary parotid infection due to C. neoformans.

Scedosporium apiospermum: changing clinical spectrum of a therapy-refractory opportunist.

Current knowledge on the opportunist Scedosporium apiospermum (teleomorph: Pseudallescheria boydii), generated over a period of more than 120 years, is reviewed. The natural environmental habitat of the fungus is unknown; nutrient-rich, brackish waters like river estuaria have been suggested. The fungus is strongly promoted by agricultural and particularly by industrial pollution.

A Rhizopus oryzae strain isolated from resected bone and soft tissue specimens from a sinonasal and palatal mucormycosis case. Report of a case and in vitro experiments of yeastlike cell development.

We report a histologically and mycologically proven sinonasal mucormycosis case causing palatal necrosis in a nondiabetic patient with renal failure. Mycological examination of Giemsa stained imprinted tissue preparations revealed abundant yeast-like cells besides the typical mucoraceous hyphae. The fungus was isolated from surgical specimens and identified as Rhizopus oryzae by phenotypic and genotypic tests. Laboratory studies were performed to investigate the association of the yeast-like cells observed in tissue specimens and the fungus recovered in culture. In vitro induced yeast-like cell development of the case isolate was found under certain growth conditions and documented by photomicrographs.

Phospholipase and protease activities in clinical Candida isolates with reference to the sources of strains.

The present study was aimed at determining in vitro phospholipase and protease activities in 95 clinical isolates of various Candida species (C. albicans, C. glabrata, C. guilliermondii,C.kefyr, C. krusei, C. lipolytica, C. lusitaniae, C. parapsilosis, C.rugosa and C. tropicalis). 59 (62.1%) of isolates examined were phospholipase positive and 75 (78.9.9%) were protease positive. 56 (93.3%) of C.albicans isolates tested were phospholipase producers - however only a few strains of C. glabrata and C. kefyr behaved in the same way. Protease activity was detected in 57 (95%) of C. albicans strains tested and in a few strains of C. kefyr, C.lipolytica, C. parapsilosis and C. tropicalis- the remaining isolates were negative. 56 strains of C.albicans and 2 strains of C. kefyr tested produced both phospholipase and protease.

The presence of fluconazole-resistant Candida dubliniensis strains among Candida albicans isolates from immunocompromised or otherwise debilitated HIV-negative Turkish patients.

The newly described species Candida dubliniensis phenotipically resembles Candida albicans in many respects and so it could be easily misidentified. The present study aimed at determining the frequency at which this new Candida species was not recognized in the authors' university hospital clinical laboratory and to assess antifungal susceptibility. In this study, six identification methods based on significant phenotypic characteristics each proposed as reliable tests applicable in mycology laboratories for the differentiation of the two species were performed together to assess the clinical strains that were initially identified as C. albicans. Only the isolates which have had the parallel results in all methods were assessed as C. dubliniensis. One hundred and twenty-nine C. albicans strains isolated from deep mycosis suspected patients were further examined. Three of 129 C. albicans (2 from oral cavity, 1 from sputum) were reidentified as C. dubliniensis. One of the strains isolated from oral cavity and that from the sputum were obtained at two months intervals from the same patient with acute myeloid leukemia, while the other oral cavity strain was obtained from a patient who had previously been irradiated for a laryngeal malignancy. Isolates were all susceptible in vitro to amphotericin B, with the MIC range 0.125 to 0.5 &mgr;g/ml, resistant to fluconazole, with MICs >/=64 &mgr;g/ml, and resistant to ketoconazole, with MICs >/=16 &mgr;g/ml, dose-dependent to itraconazole with a MIC range 0.25-0.5 &mgr;g/ml, and susceptible to flucytosine, with a MIC range 1-4 &mgr;g/ml.