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Human infections by pleosporalean fungi (class Dothideomycetes, phylum Ascomycota) are rarely reported. Because their identification is challenging using morphological characterization, several phylogenetic markers must be sequenced for an accurate identification and taxonomical placement of the isolates. Three isolates of clinical origin were phenotypically characterized, but due to the absence of relevant morphological traits, D1-D2 domains of the 28S nrRNA gene (LSU), the internal transcribed spacer region (ITS) of the nrRNA, and fragments of the RNA polymerase II subunit 2 (rpb 2) and translation elongation factor 1-alpha (tef 1) genes were sequenced to allow a phylogenetic analysis that would solve their phylogenetic placement. That analysis revealed that these isolates did not match any previously known pleosporalean genera, and they are proposed here as the new fungal genus, Gambiomyces. Unfortunately, the isolates remained sterile, which, consequently, made the morphological description of the reproductive structures impossible. Future studies should try to understand the behaviour of this fungus in nature as well as its characteristics as an opportunistic fungal pathogen. Molecular identification is becoming an essential tool for proper identification of Dothideomycetes of clinical origin. Lay Abstract We describe a new pleosporalen pathogenic fungus, Gambiomyces profunda , found in superficial to deep samples from a human patient. Because all strains remained sterile, the fungus was finally identified following a phylogenetic analysis by using four different molecular markers. [ABSTRACT FROM AUTHOR]

Scopulariopsis is a common fungus in the environment, characterized by its intrinsic resistance to the available antifungal drugs. Around 70 cases of infection by this fungus have been described in the literature. Pulmonary and disseminated infections are the most common and their treatment is difficult; therefore, very diverse approaches have been taken, with varied results. A successful outcome has been reported in only a few cases, generally attributed to a multitreatment strategy combining medical and surgical procedures that ultimately led to the resection of the infected tissue if possible, identification of the mould, and an aggressive long-term antifungal therapy. Although most of the infections are caused by Scopulariopsis brevicaulis , a few other species have also been linked to these cases, although molecular evidence has not been proven for all of them. On this basis, more knowledge on the epidemiology, presentation, diagnosis, treatment, and prognosis of these unusual infections would improve their management. This review aims to compile the current data on Scopulariopsis infections. [ABSTRACT FROM AUTHOR]

Candida glabrata causes difficult to treat invasive candidiasis due to its antifungal resistance, mainly to azoles. The aim of the present work was to study the role of the genes ERG11 , CDR1 , CDR2, and SNQ2 on the resistance to voriconazole (VRC) in a set of C. glabrata strains with known in vitro and in vivo susceptibility to this drug. Eighteen clinical isolates of C. glabrata were exposed in vitro to VRC, and the expression of the cited genes was quantified by real time quantitative polymerase chain reaction (q-PCR). In addition, the ERG11 gene was amplified and sequenced to detect possible mutations. Ten synonymous mutations were found in 15 strains, two of them being reported for the first time; however, no amino acid changes were detected. ERG11 and CDR1 were the most expressed genes in all the strains tested, while the expression of CDR2 and SNQ2 was modest. Our results show that gene expression does not directly correlate with the VRC MIC. In addition, the expression profiles of ERG11 and efflux pump genes did not change consistently after exposure to VRC. Although individual analysis did not result in a clear correlation between MIC and gene expression, we did observe an increase in ERG11 and CDR1 expression in resistant strains. It is of interest that considering both in vitro and in vivo results, the slight increase in such gene expression correlates with the observed resistance to VRC. [ABSTRACT FROM AUTHOR]

We report several cases of fungal infections in snakes associated with a new species within the genus Paranannizziopsis. Three juvenile Wagler's vipers (Tropidolaemus wagleri) presented with skin abnormalities or ulcerative dermatitis, and two snakes died. Histologic examination of skin from the living viper revealed hyperplastic, hyperkeratotic, and crusting epidermitis with intralesional fungal elements. The terrestrial Wagler's vipers were housed in a room with fully aquatic tentacled snakes (Erpeton tentaculatum), among which there had been a history of intermittent skin lesions. Approximately 2 months after the biopsy of the viper, a skin sample was collected from one tentacled snake (TS1) with skin abnormalities and revealed a fungal infection with a similar histologic appearance. Fungal isolates were obtained via culture from the Wagler's viper and TS1 and revealed a novel species, Paranannizziopsis tardicrescens , based on phenotypic characterization and molecular analysis. P. tardicrescens was cultured and identified by DNA sequence analysis 8 months later from a dead tentacled snake in an exhibit in an adjacent hallway and 13 months later from a living rhinoceros snake (Rhynchophis boulengeri) with two focal skin lesions. Antifungal susceptibility testing on three of four cultured isolates demonstrated potent in vitro activity for terbinafine and voriconazole. [ABSTRACT FROM AUTHOR]

Although there have been few reports of opportunistic infections (superficial and systemic) caused by coelomycetous fungi, they are becoming more frequent. Neocucurbitaria keratinophila (formerly Pyrenochaeta keratinophila), characterized by producing pycnidial conidiomata and small hyaline conidia, seems to be an emergent opportunistic pathogen in Spain. Since this fungus was first reported from human keratitis, eight strains have been isolates from clinical cases in Spain. This is a retrospective study of these fungal strains, including phenotypic and molecular characterizations, and in vitro antifungal susceptibility assays. These clinical strains were identified by sequencing four phylogenetic markers such as the internal transcribed spacer region (ITS1-5.8S-ITS2) and fragments of the 28S nrRNA (LSU), beta-tubulin (tub 2), and RNA polymerase II subunit 2 (rpb 2) genes, and by morphological characterization. All the strains tested were susceptible to the majority of antifungals, being isavuconazole the only drug that showed a poor antifungal activity. [ABSTRACT FROM AUTHOR]

The diversity of Aspergillus species in clinical samples is continuously increasing. Species under the former name Eurotium, currently accommodated in section As-pergillus of the genus Aspergillus, are xerophilic fungi widely found in the human environment and able to grow on substrates with low water activity. However, their prevalence in the clinical setting is poorly known. We have studied the presence of these species in a set of clinical samples from the United States using a multilocus sequence analysis based on the internal transcribed spacer (ITS) region of the rRNA, and fragments of the genes β-tubulin (BenA), calmodulin (CaM), and polymerase II second largest sub-unit (RPB2). A total of 25 isolates were studied and identified as follows: A. monteviden-sis (44%), A. chevalieri (36%), A. pseudoglaucus (8%), and A. costiformis (4%). A new species Aspergillus microperforatus is also proposed, which represented 8% of the isolates studied and is characterized by uniseriate conidial heads, subglobose to pyriform vesicles, rough conidia, globose to subglobose cleistothecia, and lenticular and smooth ascospores. The in vitro antifungal activity of eight clinically available antifungals was also determined against these isolates, with the echinocandins and posaconazole having the most potent activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Clinical and experimental data have shown discrepancies on the efficacy of combinations between triazoles and echinocandins. In this study, anidulafungin plus posaconazole have shown efficacy against a murine systemic infection by three strains of Aspergillus fumigatus. The combination increased mice survival and reduced burden in the kidneys over the corresponding monotherapies and voriconazole. Clearance of kidneys was observed in 62% to 100% of animals (strain dependant).We observed good in vitro- in vivo correlation when a cutoff < 1was indicative of synergy. Our results showed that the combination could be a therapeutical option, especially against infections refractory to the first line therapy. [ABSTRACT FROM AUTHOR]

Background: Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from disseminated infections. Recommended first-line treatment is voriconazole, but epidemiological cut-off values and clinical breakpoints have not been determined.Objectives: To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMérieux) and disc diffusion.Methods: Voriconazole MICs for 31 Scedosporium apiospermum strains were determined using CLSI broth microdilution, Etest and disc diffusion. Groups of mice were challenged intravenously with 1 out of 16 S. apiospermum strains (voriconazole CLSI broth microdilution MIC range: 0.125-8.0 mg/L) and treated with 40 mg/kg voriconazole orally by gavage once daily. Efficacy of voriconazole was evaluated by a statistically significant ( P  <   0.05) reduction in fungal burden in brain.Results: A categorical agreement of 90.4% was reached for CLSI broth microdilution and disc diffusion and of 93.6% for CLSI broth microdilution and Etest. Correlation of CLSI MICs and in vivo outcome was good, as mice challenged with strains with an MIC ≤2 mg/L responded to voriconazole therapy in 92.3% and those challenged with strains with an MIC ≥4 mg/L responded to voriconazole therapy in 33.3%.Conclusions: CLSI broth microdilution and Etest deliver comparable results that enable a prediction of in vivo outcome. Our results suggest that voriconazole is able to reduce fungal burden in the brain of 92.3% of all mice challenged with strains with voriconazole CLSI MICs ≤2 mg/L, while mice challenged with strains with CLSI MICs ≥4 mg/L showed limited response to voriconazole treatment. [ABSTRACT FROM AUTHOR]

Whereas echinocandins are alternatives for the treatment of invasive aspergillosis, the efficacy of anidulafungin (AFG) against Aspergillus terreus infection has not yet been explored. We have evaluated the in vitro activity, as well as the in vivo efficacy of AFG in neutropenic mice infected by A. terreus species complex. Time-kill studies showed in vitro fungistatic activity of AFG against two strains. AFG at doses of 5 and 10 mg/kg/day significantly reduced the fungal load in kidney of mice, but only the higher dose was able to prolong survival. [ABSTRACT FROM AUTHOR]

Objectives Scedosporium infections are associated with high therapeutic failure rates. Combination therapy may be an alternative approach to improve outcome. The in vitro and in vivo efficacy of micafungin plus posaconazole or plus voriconazole was investigated herein. Methods Scedosporium boydii (n = 17) and Scedosporium apiospermum (n = 26) were tested using the chequerboard method according to CLSI M38-A2 guidelines and the fractional inhibitory concentration index (FICI) was evaluated. In vivo outcome of micafungin plus posaconazole or micafungin plus voriconazole against two isolates of each of the mentioned species was evaluated in a well-established, immunocompromised, haematogenous murine model of systemic scedosporiosis. Survival and tissue burden in kidneys and brain were investigated. Results The FICI category of ‘no interaction’ was most frequent, while ‘synergism’ or ‘antagonism’ was rarely observed. FICI failed to predict the in vivo outcome of both combinatorial treatment strategies. In vivo outcome was strain-dependent rather than species-dependent, even though effects on fungal tissue burden were more pronounced for S. boydii. Both combinations improved survival significantly when compared with untreated controls and micafungin monotherapy. Voriconazole and posaconazole did not differ in their efficacy and micafungin failed to be effective. Combinations were by trend better than voriconazole and posaconazole as single therapy, but statistically significant differences were lacking. Conclusions No benefit of the azole/echinocandin combination was found when compared with voriconazole and posaconazole monotherapies. FICI failed to predict the outcome of in vivo drug combinations in the murine study. [ABSTRACT FROM PUBLISHER]

The fungal genus Pithomyces comprises numerous dematiaceous saprobic species commonly found on dead leaves and stems of a great variety of plants. Occasionally, they have been recovered from clinical specimens. We morphologically and molecularly (rDNA sequences) investigated a set of 42 isolates tentatively identified as Pithomyces recovered from clinical specimens in the United States. The predominant species were P. chartarum and P. sacchari (33.3% each), followed by Pithomyces sp. I (28.6%) and P. maydicus (4.8%). Most of the isolates were obtained from samples of superficial tissue (50%), the respiratory tract (21.4%), and the nasal region (19%). In general, these fungi were highly susceptible in vitro to the eight antifungal agents tested. [ABSTRACT FROM PUBLISHER]

Acremonium is an emerging fungal pathogen causing severe infections. We evaluated the virulence of three clinically relevant species within the genus, i.e., Acremonium kiliense (currently Sarocladium kiliense), Acremonium sclerotigenum-A. egyptiacum complex and Acremonium implicatum in a murine model of disseminated infection. Both immunocompetent and immunosuppresssed mice were infected with two inocula concentrations (2 × 106 and 2 × 108 conidia/animal) of two strains of each species. Tissue burden, mortality rate, histopathology and levels of (1→3)-β-D-glucan were used as virulence markers. None of the species of Acremonium tested was able to cause infection in immunocompetent mice. Conversely, severe infections were produced in immunocompromised mice, the spleen being the most affected organ. In general, the virulence of the Acremonium species tested was low, S. kiliense being the most virulent species. [ABSTRACT FROM PUBLISHER]

We describe an opportunistic, disseminated infection in a German shepherd dog associated with two fungal organisms not previously reported to cause disease. Lecythophora canina, a new species here described, was isolated from an osteolytic bone lesion. A fine needle aspirate of the lesion demonstrated septate hyphae. Plectospharella cucumerina (anamorph Plectosporium tabacinum) was isolated from a urine sample. Clinical manifestations were blindness, altered mentation, and osteomyelitis. Treatment with itraconazole and terbinafine for greater than one year resulted in stable clinical disease. [ABSTRACT FROM AUTHOR]

We have determined the in vitro activity of amphotericin B (AMB) and posaconazole (PSC) against Saksenaea vasiformis using broth microdilution and disk diffusion methods and determined the minimal fungicidal concentration (MFC). PSC was found to have the greatest in vitro activity in all cases and was the most efficacious in prolonging survival and reducing the fungal load in an immunocompetent murine model of disseminated infection caused by four strains of the fungus. [ABSTRACT FROM AUTHOR]

Soilborne fungal pathogens cause devastating yield losses and are highly persistent and difficult to control. During the infection process, these organisms must cope with limited availability of iron. Here we show that the bZIP protein HapX functions as a key regulator of iron homeostasis and virulence in the vascular wilt fungus Fusarium oxysporum. Deletion of hapX does not affect iron uptake but causes derepression of genes involved in iron-consuming pathways, leading to impaired growth under iron-depleted conditions. F. oxysporum strains lacking HapX are reduced in their capacity to invade and kill tomato (Solanum lycopersicum) plants and immunodepressed mice. The virulence defect of Δ hapX on tomato plants is exacerbated by coinoculation of roots with a biocontrol strain of Pseudomonas putida , but not with a siderophore-deficient mutant, indicating that HapX contributes to iron competition of F. oxysporum in the tomato rhizosphere. These results establish a conserved role for HapX-mediated iron homeostasis in fungal infection of plants and mammals. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the in vitro activity of posaconazole and amphotericin B against several clinical strains of the mucoralean fungus Apophysomyces variabilis, and their efficacy in a murine model of disseminated infection caused by that fungus. Methods The in vitro susceptibility of seven strains of A. variabilis to posaconazole and amphotericin B was determined by using a broth microdilution method. The in vivo efficacy of both drugs, posaconazole at 20 mg/kg twice daily orally by gavage and amphotericin B at 0.8 mg/kg once daily intravenously, was evaluated against six of the strains previously tested in vitro using immunocompetent mice. Results In general, MICs of both drugs were within the range of susceptibility or intermediate susceptibility. Posaconazole and amphotericin B were able to significantly reduce the percentages of positive cultures in the affected tissues. However, in general, posaconazole significantly improved survival (median, 23 days; range, 7–30 days) compared with untreated controls (median, 6 days; range, 4–7 days) and, in some cases, with respect to the animals treated with amphotericin B (median, 15 days; range, 5–30 days). Conclusions Our results demonstrate the efficacy of posaconazole in the treatment of a disseminated murine infection caused by A. variabilis. However, further clinical studies are required to ascertain the potential use in human infections caused by this fungus. [ABSTRACT FROM PUBLISHER]

Members of the Cryptococcus neoformans/C. gattii species complex are grouped into eight molecular types, differing in their epidemiology, disease severity and geographic range. Recent in vitro antifungal susceptibility studies of isolates of the complex revealed contradictory results. The objective of the present study was to assess if this variation is random or correlates with different molecular types by testing the in vitro antifungal susceptibility of 18 C. neoformans (VNI), 11 C. gattii (VGI) and 38 C. gattii (VGII) strains from Brazil to eight antifungal drugs using the CLSI microdilution method. We herein report that the molecular type VGII is the least susceptible genotype, followed by VGI and VNI. This indicates a clear correlation between antifungal susceptibilities and genotypes of the causative cryptococcosis agents, emphasizing the importance of determining the molecular type as part of the clinical diagnostic process to enable an informed decision as to the most appropriate antifungal treatment. [ABSTRACT FROM AUTHOR]

Objectives A murine model of chromoblastomycosis caused by Cladophialophora carrionii was used to compare the efficacy of posaconazole and voriconazole with that of terbinafine and itraconazole, the currently used drugs in the management of chromoblastomycosis. Methods Athymic nude mice were infected with 2 × 107 cfu of a clinical isolate of C. carrionii. When typical lesions were established, treatments with posaconazole at 20 mg/kg/day, voriconazole at 20 mg/kg/day, itraconazole at 50 mg/kg/day or terbinafine at 250 mg/kg/day were initiated. Treatment efficacy was evaluated for 4 months by measuring the size of the lesions, observing any histopathological changes and culturing the excised tissue. Results Posaconazole was the only drug that reduced the initial lesion size, while voriconazole and terbinafine reduced growth relative to controls. Conclusions This study suggests that the newer triazoles have potential in the treatment of chromoblastomycosis caused by C. carrionii. [ABSTRACT FROM PUBLISHER]

During a survey on the incidence of Aspergillus in clinical environments, we found some interesting isolates that were morphologically similar to Aspergillus parasiticus, but differed in the color of the colonies and in the pattern of their conidial ornamentation. In the present study, those isolates were characterized using a polyphasic approach. A phylogenetic analysis was carried out, based on partial fragments of the acetamidase ( amdS) and O-methyltransferase ( omtS) genes and the internal transcribed spacer (ITS) region of rDNA. This information was combined with a detailed morphological and physiological study that included aflatoxin production and assimilation profiles of different carbon and nitrogen sources. The phenotypic and genotypic results support the proposal of a new species, Aspergillus novoparasiticus, phylogenetically placed in a distinct sister clade to that of A. parasiticus. The former has lobate-reticulate conidia and does not produce aspergillic acid on AFPA or organic acids on CREA, while A. parasiticus has echinulate conidia and produces aspergillic and organic acids. In addition, this new species, as well as A. parasiticus, produces aflatoxins B1, B2, G1 and G2. [ABSTRACT FROM AUTHOR]

Clinical experience in the management of opportunistic infections, especially those caused by less common fungi, is, due to their rarity, very scarce; therefore, the most effective treatments remain unknown. The ever-increasing numbers of fungal infections due to opportunistic fungi have repeatedly proven the limitations of the antifungal armamentarium. Moreover, some of these fungi, such as Fusarium spp. or Scedosporium spp., are innately resistant to almost all the available antifungal drugs, which makes the development of new and effective therapies a high priority. Since it is difficult to conduct randomized clinical trials in these uncommon mycoses, the use of animal models is a good alternative for evaluating new therapies. This is an extensive review of the numerous studies that have used animal models for this purpose against a significant number of less common fungi. A table describing the different studies performed on the efficacy of the different drugs tested is included for each fungal species. In addition, there is a summary table showing the conclusions that can be derived from the analysis of the studies and listing the drugs that showed the best results. Considering the wide variability in the response to the antifungals that the different strains of a given species can show, the table highlights the drugs that showed positive results using at least two parameters for evaluating efficacy against at least two different strains without showing any negative results. These data can be very useful for guiding the treatment of rare infections when there is very little experience or when controversial results exist, or when treatment fails. [ABSTRACT FROM PUBLISHER]

Two new species in the order Mucorales, Mucor velutinosus and Mucor ellipsoideus, isolated from human clinical specimens in the USA, are described and illustrated. The former species is similar to Mucor ramosissimus, from which it can be differentiated by its ability to grow at 37°C and produce verrucose sporangiospores. Mucor ellipsoideus is also able to grow and sporulate at 37°C like M. indicus, the nearest phylogenetic species in this study, however, the former has narrow ellipsoidal sporangiospores in contrast to the subglobose to ellipsoidal sporangiospores of M. indicus. Analysis of the sequences of the ITS and the D1-D2 regions of the rRNA genes confirmed the novelty of these species. The in vitro antifungal susceptibility of the new species showed that amphotericin B was active against all isolates and posaconazole and itraconazole showed low activity. [ABSTRACT FROM AUTHOR]

The virulence of Exophiala dermatitidis, E. oligosperma and E. xenobiotica, three of the most common members of the genus that cause human infections, was evaluated using experimental models of disseminated infection in immunocompromised mice. Exophiala dermatitidis, and to a lesser extent E. oligosperma, were the two species causing the highest mortality, while mice infected with E. xenobiotica had the lowest mortality. Tissue burden and histopathology studies demonstrated the neurotropism of E. dermatitidis, while E. oligosperma and E. xenobiotica had a limited capacity for invading brain tissue. These models could be useful for testing new therapies against Exophiala infections. [ABSTRACT FROM AUTHOR]

We have developed two murine models of disseminated infections by Neoscytalidium dimidiatum, an emerging dematiaceous fungus. Immunosuppressed mice were challenged through the lateral tail vein with 1×105 or 1×106 CFU/ml and immunocompe-tent animals with 1×106 or 1×107 CFU/ml. N. dimidiatum var. dimidiatum was more virulent than the nonpigmented variety, N. dimidiatum var. hyalinum. All mice infected with N. dimidiatum var. dimidiatum died within 8 days while those infected with N. dimidiatum var. hyalinum survived to the end of the experiment. Fungal load in tissue was also higher in animals inoculated with N. dimidiatum var. dimidiatum. In general, of the five organs tested, spleens and kidneys were most affected. [ABSTRACT FROM AUTHOR]

Objectives: We have evaluated the efficacy of posaconazole, itraconazole and amphotericin B in murine models of disseminated infection caused by Exophiala spp. [ABSTRACT FROM PUBLISHER]

Scedosporium apiospermum has traditionally been thought of as the anamorph of Pseudallescheria boydii (Microascaceae, Ascomycota), but recent molecular studies has demonstrated that they are different species. Since a teleomorph was not observed among isolates recently identified as S. apiospermum, we investigated whether this species could be heterothallic. In this study, 15 isolates of S. apiospermum were paired in all possible combinations, including self-pairings. Several combinations produced fertile ascomata typical of the genus Pseudallescheria, while all isolates were self-sterile. The isolates were grouped into two different mating types. Crosses among F1 progeny ascospores demonstrated a bi-allelic heterothallic mating system. The new species Pseudallescheria apiosperma, teleomorph of S. apiospermum, is proposed and described. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pseudallescheria boydii sensu lato is a complex of species involved in severe human infections. We have evaluated, using a murine model, the virulence of 2 strains of each of the most representative species of the complex, i.e., P. boydii sensu stricto, P. minutispora, Scedosporium apiospermum, S. aurantiacum and S. dehoogii. We used two different inocula, i.e., 5×104 conidia/ml (for immunosuppressed animals) and 1×106 conidia/ml (for immunocompetent animals), which were administered intravenously. Scedosporium aurantiacum and S. dehoogii were the most virulent species, causing the death of 80% and 70% of the immunocompetent mice, respectively. The remaining species only killed 0-20% of the animals. [ABSTRACT FROM AUTHOR]

Scedosporium species are increasingly encountered opportunistic fungal pathogens not only in immunocompromised patients but are also significant primary pathogens in immunocompetent individuals. The environmental reservoir of these fungi is uncertain and the epidemiology and mode of transmission are not well-defined. Conventional phenotypic methods are of limited use for epidemiological purposes since they are insensitive and inadequately discriminatory. Molecular techniques not only enable accurate phylogenetic delineation of species but also provide the means for rapid, reliable genotyping of strains for epidemiological and population genetic studies. This review discusses the methods that have been applied for genotyping of these increasingly important pathogens. [ABSTRACT FROM AUTHOR]

We tested ten day courses of amphotericin B (AMB), micafungin (MFG), voriconazole (VRC), flucytosine (5FC) and posaconazole (PSC) alone and in double or triple combinations in the treatment of disseminated infections caused by Cladophialophora bantiana in a murine model. Animals were monitored for survival for 40 days. We found that PSC at 100 mg/kg or 5FC at 180 mg/kg prolonged survival over controls. The combinations PSC+MFG and PSC+5FC improved survival compared to MFG and 5FC alone, but were not superior to PSC alone. The triple combination of PSC+MFG+5FC improved the survival with respect to both the control group and the component monotherapies, but all the animals died during the experiment. When treatment with this triple therapy was extended up to 30 days, half of the animals survived for at least 10 months. Combination therapy with the three drugs (PSC, MFG and 5FC) appears to be a promising option for the treatment of C. bantiana infections. [ABSTRACT FROM AUTHOR]

Sporothrix schenckii var. luriei is a very rare pathogen reported on four occasions from human infections, but only isolated from one case in Africa. Here, it is proposed as a species different from Sporothrix schenckii on the basis of phenotypic characteristics and a multilocus sequence analysis. [ABSTRACT FROM AUTHOR]

Here we report on two isolates of Candida glabrata recovered from urine samples collected from of an Intensive Care Unit patient. D1/D2 and ITS 1+2 rDNA sequence analysis confirmed its identification. The isolates were cholesterol dependent and resistant to Amphotericin B. [ABSTRACT FROM AUTHOR]

Identification of unusual fungal isolates is a major challenge for the clinical laboratory. This report describes the isolation of Candida africana from a patient with vaginitis. This is a doubtful species which possibly represents atypical strains of Candida albicans. Candida africana can be separated morphologically and physiologically from C. albicans but not genetically. The analysis of 26S rRNA gene showed near 100% homology between C. africana and C. albicans. [ABSTRACT FROM AUTHOR]

Objectives: To develop proper treatments for patients who do not respond to current antifungal treatments, we tested new combinations of antifungal drugs for treating disseminated infections by Candida glabrata in a murine model. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Numerous patients were diagnosed with aspergillosis in a nosocomial outbreak caused by Aspergillus fumigatus and Aspergillus flavus . Thirty-three isolates of the former and 28 isolates of the latter were collected from the hospital environment and from the patients and studied for genetic relatedness by random amplified microsatellites (RAMS) analysis, in which two polymorphic regions were tested. Twenty-eight genotypes of A. fumigatus and 23 genotypes of A. flavus were identified. Four patients were infected by two isolates with the same genotype as the environmental isolates. One clinical genotype was shared by three patients and another was shared by two patients. We found that RAMS was useful for fingerprinting Aspergillus spp. [ABSTRACT FROM AUTHOR]

We established a reproducible lethal disseminated infection by the opportunistic fungus Scedosporium prolificans in an immunosuppressed murine model. We compared the effectiveness of the combined administration of liposomal amphotericin B (LAMB) and granulocyte colony-stimulating factor (G-CSF) with that of either agent alone and with that of amphotericin B deoxycholate (AMB). LAMB + G-CSF and LAMB treatments improved survival significantly with respect to the untreated control. The mean survival times of these three groups were 13.2, 9.1 and 7.9 days, respectively. Culture results in terms of colony counts for samples of deep organs were lower in mice treated with the combined therapy, although differences were not significant. Combined LAMB + G-CSF therapy could be a promising approach for the treatment of disseminated infections of S. prolificans, although further studies are required to determine the most appropriate doses. [ABSTRACT FROM AUTHOR]

Aeromonas popoffii is the most recent species within the genus Aeromonas described from freshwater. In our study this species was also recovered from this habitat and for the first time from seawater. Most of the virulence factors known in Aeromonas spp. (aerolysin/hemolysin, serine protease, lipases and DNases) were highly prevalent in this species. Third-generation cephalosporins and quinolones were the most active antimicrobial agents against A. popoffii. [Copyright &y& Elsevier]

The effect of inoculum form, i.e. ungerminated conidia, germinated conidia and hyphae on the in vitro antifungal susceptibility of 12 strains belonging to Aspergillus spp. was compared using a broth microdilution method. The isolates were tested three times on different days against amphotericin B, itraconazole and ketoconazole. There were no significant differences between MICs obtained with the three types of inoculum (P > 0.05) for any antifungal tested. The degree of reproducibility of the tests was high (>or=75%) for all antifungals with each type of inoculum, except for itraconazole (58.3%) when the inoculum was prepared with ungerminated conidia. [ABSTRACT FROM AUTHOR]

Comments on several articles concerning clinical infectious diseases. Outbreak of hemolytic uremic syndrome and bloody diarrhea; Microbiologic data regarding isolation of Aspergillus species from patients at the Detriot Medical Center from 1994 to 1998; Review of African trypanosomiasis among travelers from the United States.

The in-vitro antifungal susceptibilities of nine isolates belonging to Basidiobolus spp. and seven to Conidiobolus spp. against six antifungals (amphotericin B, ketoconazole, miconazole, itraconazole, fluconazole and flucytosine) were tested. A broth microdilution method, generally following the NCCLS guidelines, was used. Inoculum concentrations of the order of 100 cfu/mL were obtained by culturing fungi in a broth medium (Czapeck broth supplemented with 2% Tween 80 and 0.07% agar). MICs and MFCs were highly variable and isolate-dependent, with the exception of those of flucytosine which were constantly very high. In general, however, Basidiobolus spp. displayed low MICs of fluconazole, itraconazole, ketoconazole and miconazole, and Conidiobolus spp. were resistant to all antifungals tested. [ABSTRACT FROM AUTHOR]

Fungal endocarditis in premature infants has rarely been reported; only 16 cases have been described. We present a fatal case of endocarditis due to Candida albicans in a patient requiring neonatal intensive care and parenteral nutrition via a central venous catheter; there were no preexisting pathological abnormalities. The patient had sepsis with multisystem organ failure, resulting in death. A postmortem examination was performed, and the most important findings are presented. The literature on fungal endocarditis in premature infants is reviewed as well. [ABSTRACT FROM PUBLISHER]

Objectives The aim of this study was to determine the genetic variability of clinical isolates morphologically identified as Fusarium oxysporum and to assess if there are differences in antifungal susceptibility among the possible genetic clades obtained. Methods Twenty-eight isolates were molecularly characterized by sequence analysis of the elongation factor 1α gene. The antifungal susceptibilities of these isolates to 11 antifungal drugs were tested using a microdilution method. Results and conclusions We obtained four different phylogenetic clades in the molecular study. Although all the antifungals tested showed poor activity against all the genetic clades, terbinafine showed the best results. [ABSTRACT FROM AUTHOR]