当前位置:Home > 医源资料库 > 在线期刊 > 微生物临床杂志 > 2005年第43卷第4期 > Invasive Infections Caused by Trichosporon Species and Geotrichum capitatum in Patients with Hematological Malignancies: a Retrospective Multicenter Study fro

Invasive Infections Caused by Trichosporon Species and Geotrichum capitatum in Patients with Hematological Malignancies: a Retrospective Multicenter Study fro

来源:微生物临床杂志 作者:Corrado Girmenia, Livio Pagano, Bruno Martino, Dom 2007-5-10
336*280 ads

摘要: ABSTRACT Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients。 A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological disea......


    ABSTRACT

    Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.

    INTRODUCTION

    The incidence of invasive fungal infections in patients with hematological malignancies has risen over the last two decades, mainly as a result of the increased use of intensive cytotoxic therapy, allogeneic blood stem cell transplantation, and immunosuppressive therapy. Various groups have stressed the importance of new opportunistic fungal pathogens as causes of life-threatening infections (6, 102). Trichosporonosis is an uncommon but frequently fatal invasive fungal infection in immunocompromised patients, particularly those with hematological malignancies. The pathogens most commonly implicated in invasive trichosporonosis are the yeasts widely referred to as Trichosporon sp. and Geotrichum capitatum. Over the past decade, the taxonomy of the genus Trichosporon has been subjected to extensive revision on the basis of molecular data, and the previously named T. beigelii (or T. cutaneum) corresponds, in the most recent classification, to six different species: T. asahii, T. asteroides, T. cutaneum, T. inkin, T. mucoides, and T. ovoides (46, 48). Rare cases of systemic infection have also been attributed to other Trichosporon species, such as T. pullulans and T. loubieri. Geotrichum capitatum, originally known as Trichosporon capitatum, has also undergone extensive reclassification (23, 47, 110). Consensus has yet to be reached on the proper nomenclature for this organism, and it is also referred to by some authors as Blastoschizomyces capitatus (105).

    Despite the increasing attention being focused on all fungal infections, little is known about the current epidemiology of these emerging opportunistic pathogens. Therefore, we conducted a multicenter retrospective study to characterize cases of invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases and reviewed similar cases published to date in the international literature.

    MATERIALS AND METHODS

    A total of 15 hospital hematology departments located in 11 regions of Italy participated in the study. All were members of the Infection-Control Program of the Italian Group for Study of Hematologic Disease in Adults (Gruppo Italiano Malattie Ematologiche dell'Adulto ). Five of the participating centers were located in northern Italy (in Milan, Turin, Bergamo, Udine, and Bologna), six were in central Italy (in Florence, Pescara, and Ancona and in three centers in Rome), and four were in southern Italy (in Naples, Reggio Calabria, Bari, and San Giovanni Rotondo). In each center, all invasive infections caused by Trichosporon sp. or G. capitatum observed in patients with hematologic malignancies between January 1983 and December 2002 were retrospectively ascertained and reported to the study coordinator by means of a simple case report. Fungi were identified in all centers according to morphological and biochemical criteria. Morphological studies were carried out with corn meal agar by the observation of mycelium, arthroconidia, and blastoconidia. Morphological confirmation of G. capitatum isolates by the observation of the presence of anelloconidia, specific to this fungal species, was performed in only a minority of cases. Biochemical tests were performed by using either a API or VITEK system (BioMerieux Italia, Rome, Italy) or both. The Trichosporon sp. isolates from two centers (Rome and Pescara) were available for reidentification according to the new taxonomic classification by using a VITEK 2 system (BioMerieux Italia); the identification of T. asahii strains was confirmed by the PCR amplification of rRNA gene fragments by using species-specific primers as described by Sugita et al. (114, 115). For each case, data were collected on patient demographics, underlying condition, presentation and clinical characteristics of the infection, management, and outcome.

    Our analysis focused on those infections that could be classified as "proven" or "probable" according to the definitions of opportunistic invasive fungal infections published by the European Organization for Research and Treatment of Cancer Invasive Fungal Infection Cooperative Group (EORTC/IFICG) and National Institute of Allergy and Infectious Disease Mycoses Study Group (NIAID/MSG) (8).

    Invasive trichosporonosis was defined as "proven" when one or more of the following criteria were met: (i) blood cultures yielding Trichosporon species or G. capitatum in patients with temporally related clinical signs and symptoms of infection, (ii) positive CSF culture results, or (iii) biopsy specimens that were culture positive for Trichosporon species or G. capitatum and presented histopathologic evidence of fungal growth characterized by minimal septate hyphal branching, blastospores, and fragmentation of the mycelium in arthroconidia.

    Cases were defined as "probable" when all of the following criteria were met: (i) the presence of at least one host factor criterion (i.e., neutropenia, recent immunosuppressive therapy, or persisting fever refractory to appropriate broad-spectrum antibacterial treatment), (ii) one microbiological criterion, or (iii) one major clinical criterion (i.e., imaging) consistent with infection.

    The EORTC/IFICG and NIAID/MSG definitions do not provide specific indications on the significance of Trichosporon sp. and G. capitatum recovery from respiratory-tract specimens. Our experience indicates, however, that for cases of this type, the microbiological criteria provided for infections caused by molds or Cryptococcus neoformans can be applied with a good degree of reliability. Therefore, in keeping with these criteria, patients with pulmonary infiltrates and recovery of Trichosporon species or G. capitatum from sputum or bronchoalveolar lavage fluid samples in the absence of other pathogens causing opportunistic infections were considered to meet the criteria for "probable" pulmonary infection. Regardless of the isolation of the fungus from blood, invasive tissue infections were defined as focal when the involvement of a single organ was documented and as disseminated when two or more organs were involved.

    A MEDLINE-based literature search was conducted for the period 1965 to May 2004 to identify all reported cases of invasive trichosporonosis in patients with any underlying condition. The search terms used were "Trichosporon" or "Geotrichum" or "Blastoschizomyces" and "infection"; cases of superficial infection were excluded. For each case found, the following data were recorded, when available: geographical location, patient age and sex, underlying disease or condition, therapy for the underlying disease, site of infection, treatment of the infection, and outcome.

    Since the classification and nomenclature of the yeasts in question have undergone numerous modifications over the years, cases identified in our retrospective study and review of the literature were broadly classified as Trichosporon sp. infections when the causative agent was identified as any of the following: T. beigelii, T. asahii, T. asteroides, T. cutaneum, T. inkin, T. mucoides, and T. ovoides. Likewise, all infections attributed to Blastoschizomyces pseudotrichosporon, Blastoschizomyces capitatus, Trichosporon capitatum, or Geotrichum capitatum were grouped under the heading "G. capitatum infections."

    To shorten the references section, most of the papers cited in previous reviews (49, 74, 76, 77, 83, 92, 108, 118) have not been included in the References list.

    RESULTS

    Retrospective study of cases in Italy. Patient population. During the 20-year period examined in our study (January 1983 through December 2002), 52 cases of probable or proven invasive Trichosporon sp. or G. capitatum infections in patients with hematological malignancies were identified. The characteristics of these cases are summarized in Table 1. The mean age of infected patients was 40.3 years (range, 11 to 65 years), and 35 (67%) patients were male. A total of 17 of the cases were classified as Trichosporon sp. infections. They were T. asahii in 6 cases and T. pullulans in one case. In the remaining 10 cases previously identified as T. beigelii a reidentification according to the new taxonomic classification was not possible. A total of 35 cases were attributed to G. capitatum. Of the cases included in this series, 24 have been previously published (21, 22, 31, 32, 33, 39, 69, 76).

    The most common underlying hematologic malignancy was acute myeloid leukemia, which accounted for 65.4% of the cases. Prior to the onset of infection, 88.5% of the patients had received cytotoxic chemotherapy, and 86.5% had severe neutropenia (polymorphonuclear leukocytes < 100/mm3) at the time of infection.

    Epidemiology. Of the 15 participating hematological centers, 8 reported at least one case of Trichosporon sp. or G. capitatum infection during the 20-year study period. Of the 52 (44.2%) cases, 23 occurred during the first decade of the study period (1983 to 1992) in five different centers; the remaining 29 (55.8%) cases were observed between 1993 and 2002 in seven centers. The regional distribution of the infections is detailed in Fig. 1. All but 1 (97%) of the 35 G. capitatum infections occurred in central (29 cases) or southern (5 cases) Italy, and 20 (57%) cases were observed in a single institution in Rome. In particular, in this center 16 cases were observed in the period 1983 to 1985 (76) and only 4 cases were observed in the following 17 years.

    During the period 1992 to 2000, a total of 3,420 new cases of acute leukemia in patients over 12 years of age were observed in 13 of the participating centers. (These figures were not available for the other two centers, and none of the 15 centers could supply data for the years before and after the period 1992 to 2000). Of these 3,420 patients, 16 (0.5%) developed G. capitatum infections, and Trichosporon sp. infections were diagnosed in 15 (0.4%).

    Infection. Overall, 44 (84.6%) of the 52 infections were classified as "proven" on the basis of positive blood cultures (40 cases; 76.9%) or histopathology plus positive tissue culture (4 cases), while eight patients (15.4%) had probable infections (Table 1). In 24 (60%) of 40 cases of fungemia, focal or disseminated invasive tissue infection was documented; less commonly (16 cases; 40%), fever was the only sign of infection associated with fungemia. Pulmonary involvement was documented in a total of 14 (26.9%) of 52 cases (eight G. capitatum and six Trichosporon sp. infections). Eight of these were proven cases (as determined on the basis of blood culture findings in six cases and histopathologic findings in the other two). The other six patients met the criteria for probable pulmonary infection, i.e., fever that was unresponsive to broad-spectrum antibacterial therapy, multiple pulmonary infiltrates, and sputum or bronchoalveolar lavage fluid cultures that grew G. capitatum (5 cases) or Trichosporon spp. (1 case). Of the 52 patients, 2 (3.8%) had proven central nervous system infections caused by G. capitatum (focal meningitis in one case and multiple cerebral localizations with fungemia in the other). Two (3.8%) others had probable urinary tract infections documented by multiple urine cultures positive for G. capitatum or Trichosporon spp. (one case each) and sonographic evidence of renal lesions, and the remaining patient developed G. capitatum fungemia followed by documented infection of a intervertebral disk (22). Overall, 2 (11.8%) of 17 Trichosporon sp. and 14 (40%) of 35 G. capitatum infections were disseminated (P = 0.04; odds ratio, 0.20; 95% confidence interval, 0.03 to 1.16).

    Therapy and outcome. Various treatment regimens were used, but well over half (33 of 52; 63.5%) of all patients received conventional amphotericin B (alone, associated with flucytosine, or followed by fluconazole) (Table 1). The crude mortality rate was 59.6% (31 of 52 cases): 57.1% of the patients with G. capitatum infections and 64.7% infected by Trichosporon spp.

    Literature review. Infected patients. The literature search yielded 201 reports of trichosporonosis in patients with various types of predisposing conditions, including 24 of the 52 Italian cases described above, which had been reported in previous publications of ours (21, 22, 31, 32, 33, 39, 69, 76). For the present analysis, we also added the 28 unpublished cases of our series, bringing the total number to 396 cases. These included 287 cases classified under the broad heading of Trichosporon sp. infections (1, 2, 9, 10, 12, 14-19, 24, 26, 27, 31, 33, 34, 36, 42-45, 49, 50, 53-55, 57, 58-63, 66-69, 71-75, 79-85, 87-94, 98, 103, 104, 111, 112, 116-120, 123, 127-132, 134), 99 infections assigned to the category of G. capitatum infections (3, 4, 13, 20-22, 25, 32, 35, 37-39, 50, 52, 70, 76, 77, 93, 95, 97, 100, 101, 106,108, 133), 8 infections caused by T. pullulans (56, 64, 65, 86, 109), and 2 attributed to T. loubieri (78, 96). The patient characteristics and geographic origins of the cases are summarized in Table 2. The male/female ratio was 2:1 for both Trichosporon sp. and G. capitatum infections. Hematological diseases, peritoneal dialysis, and solid tumors were the three most commonly reported underlying diseases or conditions in patients with Trichosporon sp. infection (62.8, 8.3, and 6.8% of the cases, respectively). The 287 infections we assigned to the category of Trichosporon spp. included 28 cases (all reported after 1995) in which the yeast was identified, in accordance with the revised classification, as T. asahii (17 infections, including 10 in patients with hematological diseases) (1, 16, 26, 36, 58, 81, 84, 98, 131, 132, plus 6 cases from the present series); T. inkin (5 infections, 2 in patients with hematological malignancies) (19, 72, 74, 84, 104); T. mucoides (4 infections, none involving patients with hematological malignancies) (45, 92); and T. cutaneum or T. asteroides (each responsible for 1 infection, both involving patients with hematological malignancies) (18, 66). The vast majority of G. capitatum and T. pullulans infections occurred in patients with hematological disease (91.7 and 75%, respectively).

    The geographic distribution of the reported cases of trichosporonosis varied according to the pathogen involved. Trichosporon sp. and T. pullulans infections were reported in similar numbers on all the continents, whereas 86 (86.9%) of the 99 cases of G. capitatum infection were observed in Europe, in particular, in Italy (38 cases), Spain (30 cases), and France (7 cases). These three Mediterranean countries were thus the source of almost 90% of the European reports of G. capitatum disease and roughly three-fourths of all reports in the world literature.

    Table 3 shows the clinical characteristics of the 262 cases of invasive trichosporonosis documented for patients with underlying hematological disease. Well over half of these were suffering from acute leukemia (68, 84, and 50% of patients with Trichosporon sp., G. capitatum, and T. pullulans infections, respectively). Overall, 87% of the infected patients had been treated with conventional cytotoxic chemotherapy, and 11% had received allogeneic or autologous blood stem cell transplants. Analysis of cases in which site involvement was specified revealed that the fungal pathogen was isolated from the blood in the majority of patients (74.7% of those infected with Trichosporon sp. infections, 77.3% with G. capitatum infections, and 50% of those with T. pullulans infections). In only a few cases (3.2% for Trichosporon spp. and 1.1% for G. capitatum) the infection was related to a central venous catheter. Around 50% of all Trichosporon sp. and G. capitatum infections were classified as disseminated (defined as involvement of two or more organs, with or without fungemia). Disease was restricted to the lungs in fewer than 20% of all cases (16% of patients with Trichosporon sp. infection, 19% of those infected with G. capitatum). Focal hepatosplenic involvement was reported in 3.2 and 3.4% of Trichosporon sp. and G. capitatum infections, respectively. Crude mortality rates were higher for Trichosporon spp. (77%) than for G. capitatum (55.7%) (P < 0.001; odds ratio, 2.07; 95% confidence interval, 1.45 to 4.91).

    Information on antifungal treatment and outcome were reported for 128 of the Trichosporon sp. infections and 83 of those caused by G. capitatum (Table 4). All 22 patients who received no antifungal treatment died. Conventional amphotericin B, alone or associated with flucytosine, fluconazole, or itraconazole, was the drug most frequently employed in the initial antifungal regimen, as it was used in 90 (79.6%) of 113 Trichosporon sp. infections and 47 (61.8%) of 76 G. capitatum infections. Voriconazole was employed as initial antifungal regimen in only two cases of patients with G. capitatum infection who died. For both types of infection, survival rates in patients treated with combined therapy were similar to those for patients who received a single drug.

    DISCUSSION

    The first cases of G. capitatum and T. beigelii infections were reported in 1965 and 1970, respectively (38, 130). Later, in 1988, Trichosporon pullulans (recently renamed Guehomyces pullulans) (34) infection was described (56), and in 2003 reports of invasive infections caused by T. loubieri began to appear in the literature (78, 96). In 1992 the classification of members of the genus Trichosporon was substantially revised by Gueho et al. (46), and few years later a new classification was proposed by Sugita et al. (113-115) on the basis of analysis of 26S rRNA sequences. It is now widely accepted that this genus includes 17 species (113), including the 6 that were previously classified as a single species referred to as T. beigelii (or, formerly, T. cutaneum). These six species, T. asahii, T. asteroides, T. cutaneum, T. inkin, T. mucoides, and T. ovoides, are all recognized as potential human pathogens, and it has been suggested that each is associated with different types of infection. T. cutaneum and T. asteroides, for example, seem to be linked with superficial infections, while T. ovoides and T. inkin are involved in white piedra of the scalp and pubic area, respectively. T. asahii and T. mucoides have also been isolated from a few patients with white piedra, but they are usually associated with deep-seated infections (48, 113). It is difficult, however, to confirm these correlations, since, in many of the reports in the literature, isolates are identified using the older terms, T. beigelii or T. cutaneum. To determine which of the newly defined species are the causes of these infections, these isolates would all have to be reidentified, and in many cases, this is probably not feasible. Our search for reports of Trichosporon sp. infections yielded 28 cases (including 6 from the present series) in which the yeast was identified according to the new taxonomic classification. All six species were reported as causative agents of invasive disease, and all but T. mucoides were implicated in invasive infections in patients with hematological malignancies. Importantly, out of the 16 isolates of our series previously designated as T. beigelii, the six available for reidentification were all T. asahii according to their morphological characteristics and biochemical and molecular profiles.

    There is currently no standard classification for Geotrichum capitatum (23, 47, 105, 110). It was originally known as Trichosporon capitatum and classified among the basidiomycetes. Later, however, in light of its cell wall structure and septal pores and its tendency to produce numerous arthroconidia and few blastoconidia, it was considered to be an ascomycete. The appropriateness of this classification was further supported by the discovery of its sexual form (teleomorph), Dipodascus capitatus (23, 37, 110), and it was thus assigned to the genus Geotrichum. The subsequent discovery of its ability to produce anelloconidia, as well as arthroconidia and blastoconidia, led Salkin to reclassify G. capitatum as the single species of a new genus: Blastoschizomyces capitatus (105). However, from a taxonomic point of view, some authors maintain that G. capitatum is the correct anamorphic name (48, 108).

    G. capitatum and Trichosporon spp. are generally indistinguishable from one another on the basis of colony morphology alone. Both form arthroconidia as well as blastoconidia. G. capitatum can also produce anelloconidia, which unfortunately may be misidentified as arthroconidia or blastoconidia. Therefore, these two species are usually differentiated by their carbohydrate assimilation patterns and other biochemical properties. Geotrichum candidum is a further species with similar colony findings which is differentiated from the other two species by morphology (it produces only arthroconidia) and by biochemical properties.

    Our literature review demonstrates that while opportunistic infections with Trichosporon species or G. capitatum can occur in various types of immunocompromised patients, those with hematological malignancies are by far the most common victims of these infections. Patients of this type accounted for 92, 63, and 75% of invasive G. capitatum, Trichosporon sp., and T. pullulans infections, respectively, and one of the two reported patients with T. loubieri infection also had hematologic disease. Of the hematological malignancies mentioned in the reports we reviewed, acute leukemia, acute myeloid leukemia in particular, was the underlying disease most frequently associated with all these infections. Most of the infected patients had been treated with conventional cytotoxic chemotherapy, and very few had received blood stem cell transplants. The infections usually occurred during a period of profound neutropenia (neutrophil count, less than 100/mm3).

    Although acute leukemia is the major underlying condition in trichosporonosis, its incidence seems to be low even in this group. On the basis of our retrospective study of Italian cases, the incidence rates for Trichosporon sp. and G. capitatum infections among patients with acute leukemia were only 0.4 and 0.5%, respectively (four cases of Trichosporon spp. and five cases of G. capitatum per 1,000 adult patients with acute leukemia). It is important to recall, however, that retrospective ascertainment of documented cases of trichosporonosis (and all other fungal diseases) reveals little more than the tip of the mycological iceberg. Unfortunately, there is little information in the literature on the incidence of these infections. In a study of 353 hematology patients undergoing chemotherapy or allogeneic bone marrow transplantation, G. capitatum and Trichosporon sp. systemic infections were demonstrated with one (0.3%) and two (0.6%) patients, respectively (50). Their low epidemiological impact seems to be confirmed by a surveillance study of fungemia in cancer patients conducted by the IFICG/EORTC (125). In this study, which involved 30 centers and lasted 2 years (1992 to 1994), 269 cases of fungemia were reported but only 5 were caused by G. capitatum (2 cases) or Trichosporon spp. (3 cases) (unpublished data). On the other hand, the risk of underestimation has been highlighted by findings from an autopsy survey conducted at a university hospital in Japan (118). During the 10-year study period (1983 to 1992), disseminated Trichosporon sp. infection was found in 7 (7.7%) of 203 autopsy patients with malignant disease, and only two of these infections had been etiologically diagnosed before death occurred. The others had been misdiagnosed as candidiasis on the basis of clinical findings.

    Our experience and review of the literature suggest that the geographic distribution of trichosporonosis is by no means homogeneous. For example, although the 15 hematological centers participating in our study were uniformly distributed throughout the Italian peninsula, all but one of the 35 G. capitatum infections reported had occurred in central and southern regions. Furthermore, 20 of the 35 infections occurred in a single center in Rome, whereas in seven of the participating centers, there was not one single case of trichosporonosis during the entire 20-year period examined. It should be underlined that in the Roman institution, the distribution of G. capitatum infections was not homogeneous over the years. In fact, 16 of the 20 cases were observed in the period 1983 to 1985 (76) and only 4 cases were observed during the ensuing 17 years. An active search for G. capitatum was performed during the first period, but an environmental source of the infection was not found (76). On the other hand, although it does not take the Roman cluster of G. capitatum infections into account, the hypothesis of a peculiar geographic distribution of this mycosis continues to be valid. Underdiagnosis might be suspected in some centers, yet all of the hospitals involved in this study had reference microbiology laboratories fully capable of characterizing fungal isolates. Moreover, the case ascertainment rate in Trichosporon sp. and G. capitatum infections is probably higher than it is with other fungal infections. In fact, the high rate of isolation of these yeasts from the bloodstream (>74%) during a deep infection is in sharp contrast to those reported for most of other opportunistic fungi: for Candida spp., <50% (7); for Aspergillus spp., 10% (40); for Fusarium spp., 56% (11).

    Regional variations at the global level also emerged from an earlier review of the literature published through 1988 (76). At this point, Geotrichum capitatum and Trichosporon sp. infections were both observed almost exclusively in the United States and Europe. However, while G. capitatum infections were reported more frequently in Europe (85% of all cases) than in the United States (10%), the frequencies of Trichosporon spp. were reversed (15% of cases were reported in Europe and 78% of cases were reported in the United States). Our review, which also included papers published in the last 16 years, indicates that there is still a significantly higher frequency of G. capitatum infections in Europe, which now accounts for 87% of the reported cases. Furthermore, 87% of the European cases occurred in Italy, Spain, and France. This finding, together with the marked clustering of our cases in central and southern Italy, seems to suggest that climatic factors might play a selective role in the epidemiology of G. capitatum infections. As for Trichosporon spp., the previously noted concentration of these infections in the United States was not confirmed by our review. Only around one-third of all reported cases currently come from North America, and similar percentages are now registered for Europe and Asia.

    Similar pictures emerge from data collected during the ARTEMIS DISK Surveillance Study, a very recent prospective study conducted in more than 30 countries to identify global trends in the susceptibility of yeast pathogens to fluconazole and voriconazole (51). Isolates collected between June 1997 and December 2002 (unpublished data; reported with permission) included 81 Trichosporon sp. strains and 40 G. capitatum strains. While the former were recovered with roughly identical frequencies in Europe, the Americas, and Asia, 32 (80%) of the 40 G. capitatum isolates came from Europe, and over half (18 of 32; 56.3%) of the European isolates were recovered in Italy.

    The clinical features of trichosporonosis frequently resemble those of invasive candidosis, although there are some significant differences. Trichosporon spp. and G. capitatum are isolated from blood in over 70% of invasive infections, and approximately two-thirds of the reported cases of fungemia are associated with clinically or microbiologically documented invasive tissue localization; in a very small number of cases a central venous catheter is the portal of entry of the infection. These clinical features are in contrast with those observed in cancer patients with candidemia, as shown in a large prospective European study on candidemia in cancer patients in which only 10% of patients had a clinically or microbiologically-histologically documented organ involvement and a correlation of fungemia with a central venous catheter was demonstrated in 31% of cases (125). The EORTC/IFICG and NIAID/MSG definitions provide no specific indications on the significance of Trichosporon sp. and G. capitatum recovery from respiratory-tract specimens (8). Since both microorganisms are potential components of the normal microbial flora of the human digestive and respiratory tracts, it may be difficult to distinguish between colonization and infection. Several groups, however, have demonstrated that the isolation of these yeasts from superficial sites is significantly correlated with the development of invasive infection (50, 54, 76, 128). In a 10-year study at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, for example, Trichosporon spp. were isolated from 79 patients (54). For 60 of these patients, the isolation was believed to reflect colonization, but deep infections were ultimately documented in the remaining 19. Of particular interest is the fact that invasive pulmonary infections were subsequently documented for six of the nine patients whose sputum or bronchial lavage specimens had repeatedly grown Trichosporon spp. In another surveillance study (128), isolates of Trichosporon spp. or G. capitatum were recovered from 15 patients (any site): five were diagnosed as infected, five as possibly infected, and five as colonized. In the latter group, colonization was intermittent and transient. Our group at the Dipartimento di Biotecnologie Cellulari ed Ematologia of the University "La Sapienza" in Rome conducted epidemiologic surveys of G. capitatum colonization and infection during the periods 1983 to 1985 (76) and 2001 to 2003 (unpublished data). During the 6 years covered by these two surveys, the yeast was isolated from superficial sites (sputum, oral swab, stool, urine) for 26 patients. For eight (31%) of these patients, stool, urine, or oral colonization was transient, and their clinical courses were all uneventful. However, 13 (50%) cases ultimately satisfied the published criteria for proven invasive infections, and five other patients had radiologically documented diffuse alveolar infiltrates, with sputum yielding G. capitatum in the absence of microbiological data supporting other infectious etiologies. Collectively, these experiences support the view that the clinical significance of isolation of these pathogens from sputum in neutropenic patients seems to be comparable with that of molds and Cryptococcus neoformans, and for this reason, we and other investigators (77) feel that in the absence of other identifiable pathogens, the recovery of Trichosporon spp. or G. capitatum from respiratory-tract specimens of patients with clinically documented pneumonia is indicative of probable pulmonary trichosporonosis.

    Analysis of the cases reported in our study and those described in the literature reveals no significant differences in the clinicopathological features of deep-seated G. capitatum, Trichosporon sp., and T. pullulans infections in patients with hematological malignancies. However, the rate of mortality attributable to Trichosporon spp. and G. capitatum in this population appears to be higher than that associated with invasive Candida infections (107, 125). In particular, the prognosis was significantly worse for patients with Trichosporon sp. infections.

    The optimal therapy for trichosporonosis has yet to be identified. In our series and in the cases found in the literature, conventional amphotericin B, alone or associated with other antifungal agents, was the drug most frequently employed in first-line therapy of both Trichosporon sp. and G. capitatum infections. The low number of cases treated with alternative antifungal regimens does not allow any comparative evaluation of the efficacy of these strategies. Several investigators have proposed dual-drug therapy with amphotericin B and flucytosine as a valid option for both types of trichosporonosis (76, 94, 127), but we found no evidence in the literature that this (or any other) drug combination was more effective than single-drug regimens. As for the newer antifungal drugs, it is currently impossible to make any predictions of their clinical efficacy. The literature contains reports of only a few cases in which voriconazole or caspofungin was used as initial or salvage antifungal therapy (43, 77, 101).

    However, in vitro susceptibility findings can be a useful guide in selecting an antifungal regimen for trichosporonosis. In vitro resistance to amphotericin B has been detected in a number of Trichosporon sp. strains isolated from neutropenic patients with disseminated trichosporonosis that was refractory to this drug (127). Several groups have demonstrated the in vitro activity of azole antifungals against members of the Trichosporon genus, and these drugs have produced favorable responses in animal models (4, 5, 126, 127). However, relatively high fluconazole MICs have been found for some Trichosporon isolates (121, 122), and multidrug resistance to amphotericin B, flucytosine, fluconazole, and itraconazole has also been reported (131). In recent studies the new triazoles, voriconazole, posaconazole, and ravuconazole, have displayed potent in vitro activity against isolates of T. asahii and other Trichosporon species (99), and Falk et al. have reported low voriconazole MICs and minimal fungicidal concentrations for multidrug-resistant isolates of T. asahii (30). The high MICs reported thus far for the novel echinocandins, caspofungin, anidulafungin, and FK463, indicate that these agents are unlikely to be effective against Trichosporon species (28, 121, 122), and a breakthrough Trichosporon sp. infection in a bone marrow transplant recipient during caspofungin prophylaxis has in fact been reported (43).

    Data on the antifungal susceptibility of G. capitatum are limited (21, 29, 39, 124). We recently investigated the in vitro activities of amphotericin B, flucytosine, fluconazole, itraconazole, and voriconazole against 23 isolates of G. capitatum (most of which were the causes of the Italian infections described above) (41). The results confirmed previous observations on the high activity of amphotericin B against this species (124) and the reduced susceptibility of certain strains to flucytosine, fluconazole, and itraconazole (21) and revealed voriconazole as a very active drug against this yeast. This profile is consistent with that reported for seven G. capitatum isolates recovered from hematology patients with deep infections in a tertiary hospital in Madrid (37).

    In conclusion, Trichosporon spp. and G. capitatum cause life-threatening invasive infections, particularly in neutropenic patients with acute leukemia. The overall incidence of these infections seems to be low, even in leukemic patients, but their distribution is by no means homogeneous, and higher frequencies are observed in certain countries and in certain hematological centers. Our literature review confirms the emergence of G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are now being seen with similar frequencies on all continents. Both yeasts cause infections that are clinically similar to invasive candidosis, but they are associated with higher bloodstream recovery rates, more frequent deep organ involvement, and a poorer prognosis. The current body of published clinical data is too limited to allow reliable conclusions on the most effective form of treatment, but in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular voriconazole, in the therapeutic armamentarium against invasive Trichosporon sp. and G. capitatum infections.

    ACKNOWLEDGMENTS

    This work was supported by a grant from Pfizer Italia.

    We thank Marian Kent for revision of the manuscript.

    Study investigators included the following members of the GIMEMA Infection Program: Paolo Ricci, Istituto di Ematologia L & A Seragnoli, Universita di Bologna; Massimo Offidani, Clinica di Ematologia, Azienda Ospedaliera Umberto I, Universita Politecnica delle Marche, Ancona; Anna Candoni, Divisione di Ematologia, Universita di Udine; Laura Cudillo, Cattedra di Ematologia, Universita di Tor Vergata, Roma; Anna Maria Nosari, Divisione di Ematologia, Ospedale Niguarda, Milano; Anna Tonso, Divisione di Ematologia, Ospedale Molinette, Torino; and Marco Picardi, Divisione di Ematologia, Universita Federico II, Napoli.

    Participating members of the GIMEMA Infection Program are listed in Acknowledgments.

    REFERENCES

    Abliz, P., K. Fukushima, K. Takizawa, R. Yang, R. Li, and K. Nishimura. 2002. Identification of the first isolates of Trichosporon asahii var. asahii from disseminated trichosporonosis in China. Diagn. Microbiol. Infect. Dis. 44:17-22.

    Al-Hedaithy, S. S. A. 2003. The yeast species causing fungemia at a university hospital in Riyadh, Saudi Arabia, during a 10-year period. Mycoses 46:275-280.

    Amft, N., A. Miadonna, M. A. Viviani, and A. Tedeschi. 1996. Disseminated Geotrichum capitatum infection with predominant liver involvement in a patient with non-Hodgkin's lymphoma. Haematologica 81:352-355.

    Anaissie, E., A. Gokaslan, R. Hachem, R. Rubin, G. Griffin, R. Robinson, J. Sobel, and G. Bodey. 1992. Azole therapy for trichosporonosis: clinical evaluation of eight patients, experimental therapy for murine infection, and review. Clin. Infect. Dis. 15:781-787.

    Anaissie, E., J. R. Hachem, N. C. Karyotakis, A. Gokaslan, M. C. Dignani, L. C. Stephens, and U. C. Tin. 1994. Comparative efficacies of amphotericin B, triazoles, and combination of both as experimental therapy for murine trichosporonosis. Antimicrob. Agents Chemother. 38:2541-2544.

    Anaissie, E. J. 1992. Opportunistic mycoses in the immunocompromised host: experience at a cancer center and review. Clin. Infect. Dis. 14(Suppl. 1):43-53.

    Armstrong, D. 1989. Problems in management of opportunistic fungal diseases. Rev. Infect. Dis. 11(Suppl. 7):S1591-S1599.

    Ascioglu, S., J. H. Rex, B. de Pauw, J. E. Bennett, J. Bille, F. Crokaert, D. W. Denning, J. P. Donnelly, J. E. Edwards, Z. Erjavec, D. Fiere, O. Lortholary, J. Maertens, J. F. Meis, T. F. Patterson, J. Ritter, D. Selleslag, P. M. Shah, D. A. Stevens, and T. J. Walsh. 2002. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin. Infect. Dis. 34:7-14.

    Ashpole, R. D., K. Jacobson, A. T. King, and A. E. Holmes. 1991. Cysto-peritoneal shunt infection with Trichosporon beigelii. Br. J. Neurosurg. 5:515-517.

    Barchiesi, F., V. Morbiducci, F. Ancarani, D. Arzeni, and G. Scalise. 1993. Trichosporon beigelii fungaemia in an AIDS patient. AIDS 7:139-140.

    Boutati, E. I., and E. J. Anaissie. 1997. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years' experience at a cancer center and implications for management. Blood 90:999-1008.

    Brahn, E., and P. A. Leonard. 1982. Trichosporon cutaneum endocarditis: a sequela of intravenous drug abuse. Am. J. Clin. Pathol. 78:792-794.

    Buchta, V., P. Zak, A. Kohout, and M. Otcenasek. 2001. Disseminated infection of Blastoschizomyces capitatus in a patient with acute myelocytic leukaemia. Mycoses 44:505-512.

    Campbell, C. K., A. L. Payne, A. J. Teall, A. Brownell, and D. W. Mackenzie. 1985. Cryptococcal latex antigen test positive in patient with Trichosporon beigelii infection. Lancet ii:43-44.

    Cawley, M. J., G. R. Braxton, L. R. Haith, K. J. Reilly, R. E. Guilday, and M. L. Patton. 2000. Trichosporon beigelii infection: experience in a regional burn center. Burns 26:483-486.

    Chakrabarti, A., R. K. Marhawa, R. Mondal, A. Trehan, S. Gupta, D. S. Rao Raman, S. Sethi, and A. A. Padhyet. 2002. Generalized lymphadenopathy caused by Trichosporon asahii in a patient with Job's syndrome. Med. Mycol. 40:83-86.

    Chan, R. M., P. Lee, and J. Wroblewski. 2000. Deep-seated trichosporonosis in an immunocompetent patient: a case report of uterine trichosporonosis. Clin. Infect. Dis. 31:621.

    Chang, S. E., K. J. Kim, W. S. Lee, J. H. Choi, K. J. Sung, K. C. Moon, and J. K. Koh. 2003. A case of Trichosporon cutaneum folliculitis and septicaemia. Clin. Exp. Dermatol 28:37-38.

    Chaumentin, G., A. Boibieux, M. A. Piens, C. Douchet, P. Buttard, J. L. Bertrand, and D. Peyramond. 1996. Trichosporon inkin endocarditis: short-term evolution and clinical report. Clin. Infect. Dis. 23:396-397.

    Cheung, M. Y., N. C. Chiu, S. H. Chen, H. C. Liu, C. T. Ou, and D. C. Liang. 1999. Mandibular osteomyelitis caused by Blastoschizomyces capitatus in a child with acute myelogenous leukaemia. J. Formos. Med. Assoc. 98:787-789.

    D'Antonio, D., A. Mazzoni, A. Iacone, B. Violante, M. A. Capuani, F. Schioppa, and F. Romano. 1996. Emergence of fluconazole-resistant strains of Blastoschizomyces capitatus causing nosocomial infections in cancer patients. J. Clin. Microbiol. 34:753-755.

    D'Antonio, D., R. Piccolomini, G. Fioritoni, A. Iacone, S. Betti, P. Fazii, and A. Mazzoni. 1994. Osteomyelitis and intervertebral discitis caused by Blastoschizomyces capitatus in a patient with acute leukemia. J. Clin. Microbiol. 32:224-227.

    de Hoog, G. S., M. T. Smith, and E. Gueho. 1986. A revision of the genus Geotrichum and its teleomorphs. Stud. Mycol. 29:1-131.

    del Palacio, A., A. Perez-Revilla, R. Albanil, T. Sotelo, and D. C. Kalter. 1990. Disseminated neonatal trichosporosis associated with the hemophagocytic syndrome. Pediatr. Infect. Dis. J. 9:520-522.

    DeMaio, J., and L. Colman. 2000. The use of adjuvant interferon-gamma therapy for hepatosplenic Blastoschizomyces capitatus infection in a patient with leukemia. Clin. Infect. Dis. 31:822-824.

    Ebright, J. R., M. R. Fairfax, and J. A. Vazquez. 2001. Trichosporon asahii, a non-Candida yeast that caused fatal septic shock in a patient without cancer or neutropenia. Clin. Infect. Dis. 33:e28-e30.

    Erer, B., M. Galimberti, G. Lucarelli, C. Giardini, P. Polchi, D. Baronciani, D. Gaziev, E. Angelucci, and G. Izzi. 2000. Trichosporon beigelii: a life-threatening pathogen in immunocompromised hosts. Bone Marrow Transplant. 25:745-749.

    Espinel-Ingroff, A. 1998. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J. Clin. Microbiol. 36:2950-2956.

    Espinel-Ingroff, A. 1998. In vitro activity of the new triazole voriconazole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens. J. Clin. Microbiol. 36:198-202.

    Falk, R., D. G. Wolf, M. Shapiro, and I. Polacheck. 2003. Multidrug-resistant Trichosporon asahii isolates are susceptible to voriconazole. J. Clin. Microbiol. 41:911.

    Fanci, R., P. Pecile, R. L. Martinez, A. Fabbri, and P. Nicoletti. 1997. Amphotericin B treatment of fungemia due to unusual pathogens in neutropenic patients: report of two cases. J. Chemother. 9:427-430.

    Fanci, R., and P. Pecile. 2003. Geotrichum capitatum fungemia in a patient with acute myeloid leukemia: case report. J. Chemother. 13:412-413.

    Farina, C., F. Vailati, A. Manisco, and A. Goglio. 1999. Fungaemia survey: a 10-year experience in Bergamo, Italy. Mycoses 42:543-548.

    Fell, J. W., and G. Scorzetti. 2004. Reassignment of the basidiomycetous yeasts Trichosporon pullulans to Guehomyces pullulans gen. nov., comb. nov. and Hyalodendron lignicola to Trichosporon lignicola comb. nov. Int. J. Syst. Evol. Microbiol. 54:995-998.

    Fouassier, M., D. Joly, M. Cambon, H. Peigue-Lafeuille, and P. Condat. 1998. Geotrichum capitatum infection in a neutropenic patient. Apropos of a case and review of the literature. Rev. Med. Intern. 19:431-433.

    Fournier, S., W. Pavageau, M. Feuillhade, S. Deplus, A. M. Zagdanski, O. Verola, H. Dombret, and J. M. Molina. 2002. Use of voriconazole to successfully treat disseminated Trichosporon asahii infection in a patient with acute myeloid leukaemia. Eur. J. Clin. Microbiol. Infect. Dis. 21:892-896.

    Gadea, I., M. Cueca-Estrella, E. Prieto, T. M. Diaz-Guerra, J. I. Garcia-Cia, E. Mellado, J. F. Tomas, and J. L. Rodriguez-Tudela. 2004. Genotyping and antifungal susceptibility profile of Dipodascus capitatus isolates causing disseminated infection in seven hematological patients of a tertiary hospital. J. Clin. Microbiol. 42:1832-1836.

    Gemeinhardt, H. 1965. Lungenpathogenitat von Trichosporon capitatum beim menschen. Zentbl. Bakteriol. (series A) 196:121-133.

    Girmenia, C., A. Micozzi, M. Venditti, G. Meloni, A. P. Iori, S. Bastianello, and P. Martino. 1991. Fluconazole treatment of Blastoschizomyces capitatus meningitis in an allogeneic bone marrow recipient. Eur. J. Clin. Microbiol. Infect. Dis. 10:752-756.

    Girmenia, C., M. Nucci, and P. Martino. 2001.Clinical significance of Aspergillus fungaemia in patients with haematological malignancies and invasive aspergillosis. Br. J. Haematol. 114:93-98.

    Girmenia, C., G. Pizzarelli, D. D'Antonio, F. Cristini, and P. Martino. 2003. In vitro susceptibility testing of Geotrichum capitatum: comparison of the E-test, disk diffusion, and Sensititre colorimetric methods with the NCCLS M27-A2 broth microdilution reference method. Antimicrob. Agents Chemother. 47:3985-3988.

    Gokahmetoglu, S., A. N. Koc, T. Gunes, and N. Cetin. 2002. Case reports. Trichosporon mucoides infection in three premature newborns. Mycoses 45:123-125;

    Goodman, D., E. Pamer, A. Jakubowski, C. Morris, and K. Sepkowitz. 2002. Breakthrough trichosporonosis in a bone marrow transplant recipient receiving caspofungin acetate. Clin. Infect. Dis. 35:e35-e36.

    Grauer, M. E., C. Bokemeyer, W. Bautsch, M. Freund, and H. Link. 1994. Successful treatment of a Trichosporon beigelii septicemia in a granulocytopenic patient with amphotericin B and granulocyte colony-stimulating factor. Infection 22:283-286.

    Greenberg, R. G., and T. G. Berger. 1989. Postoperative Trichosporon beigelii soft tissue infection. J. Dermatol. Surg. Oncol. 15:432-434.

    Gueho, E., G. S. de Hoog, and M. Smith. 1992. Neotypification of the genus Trichosporon. Antonie Leeuwenhoek 61:285-288.

    Gueho, E., G. S. de Hoog, M. T. Smith, and S. A. Meyer. 1987. DNA relatedness, taxonomy, and medical significance of Geotrichum capitatum. J. Clin. Microbiol. 25:1191-1194.

    Gueho, E., L. Improvisi, G. S. de Hoog, and B. Dupont. 1994. Trichosporon on humans: a practical account. Mycoses 37:3-10.

    Hajjeh, R. A., and H. M. Blumberg. 1995. Bloodstream infection due to Trichosporon beigelii in a burn patient: case report and review of therapy. Clin. Infect. Dis. 20:913-916.

    Haupt, H. M., W. G. Merz, W. E. Beschorner, W. P. Vaughan, and R. Saral. 1983. Colonization and infection with Trichosporon species in the immunosuppressed host. J. Infect. Dis. 147:199-203.

    Hazen, K. C., E. J. Baron, A. L. Colombo, C. Girmenia, A. Sanchez-Sousa, A. del Palacio, C. de Bedout, D. L. Gibbs, and the Global Antifungal Surveillance Group. 2003. Comparison of the susceptibilities of Candida spp. to fluconazole and voriconazole in a 4-year global evaluation using disk diffusion. J. Clin. Microbiol. 41:5623-5632.

    Herbrecht, R., K. L. Liu, H. Koenig, J. Walzer, P. Dufour, F. Maloisel, J. P. Bergerat, and F. Oberling. 1990. Trichosporon capitatum septicemia in immunocompromised patients. Pathol. Biol. 38:585-588.

    Higgins, E. M., D. M. Layton, R. Arya, J. Salisbury, and A. W. du Vivier. 1994. Disseminated Trichosporon beigelii infection in an immunosuppressed child. J. R. Soc. Med. 87:292-293.

    Hoy, J., K. C. Hsu, K. Rolston, R. L. Hopfer, M. Luna, and G. P. Bodey. 1986. Trichosporon beigelii infection: a review. Rev. Infect. Dis. 8:959-967.

    Hsiao, G. H., C. C. Chang, J. C. Chen, W. L. Kuo, and S. F. Huang. 1994. Trichosporon beigelii fungemia with cutaneous dissemination. A case report and literature review. Acta Dermatol.-Venereol. 74:481-482.

    Hughes, C. E., D. Serstock, B. D. Wilson, and W. Payne. 1988. Infection with Trichosporon pullulans. Ann. Intern. Med. 108:772-773.

    Hung, C. C., S. C. Chang, Y. C. Chen, H. F. Tien, and W. C. Hsieh. 1995. Trichosporon beigelii fungemia in patients with acute leukemia: report of three cases. J. Formos. Med. Assoc. 94:127-131.

    Itoh, T., H. Hosokawa, U. Kohdera, N. Toyazaki, and Y. Asada. 1996. Disseminated infection with Trichosporon asahii. Mycoses 39:195-199.

    Jameson, B., R. L. Carter, J. G. Watson, and R. J. Hay. 1981. An unexpected fungal infection in a patient with leukaemia. J. Clin. Pathol. 34:267-270.

    Kahana, D. D., O. Cass, J. Jessurun, S. J. Schwarzenberg, H. Sharp, and K. Khan. 2003. Sclerosing cholangitis associated with trichosporon infection and natural killer cell deficiency in an 8-year-old girl. J. Pediatr. Gastroenterol. Nutr. 37:620-623.

    Kataoka-Nishimura, S., H. Akiyama, K. Saku, M. Kashiwa, S. Mori, S. Tanikawa, H. Sakamaki, and Y. Onozawa. 1998. Invasive infection due to Trichosporon cutaneum in patients with hematologic malignancies. Cancer 82:484-487.

    Kim, J. C., Y. S. Kim, C. S. Park, J. M. Kang, B. N. Kim, J. H. Woo, J. Ryu, and W. G. Kim. 2001. A case of disseminated Trichosporon beigelii infection in a patient with myelodysplastic syndrome after chemotherapy. J. Korean Med. Sci. 16:505-508.

    Ko, W. J., N. C. Chien, N. K. Chou, S. S. Wang, S. H. Chu, and S. C. Chang. 2000. Infection in heart transplant recipients: seven years' experience at the National Taiwan University Hospital. Transplant. Proc. 32:2392-2395.

    Kunova, A., J. Godal, J. Sufliarsky, S. Spanik, T. Kollar, and V. Krcmery, Jr. 1996. Fatal Richosporon pullulans breakthrough fungemia in cancer patients: report of three patients who failed on prophylaxis with itraconazole. Infection 24:273-274.

    Kunova, A., D. Sorkovska, J. Sufliarsky, and V. Krcmery, Jr. 1996. First report of catheter associated Trichosporon pullulans breakthrough fungaemia in a cancer patient. J. Infect. 32:70-71.

    Kustimur, S., A. Kalkanci, K. Caglar, M. Dizbay, F. Aktas, and T. Sugita. 2002. Nosocomial fungemia due to Trichosporon asteroids: firstly described bloodstream infection. Diagn. Microbiol. Infect. Dis. 43:167-170.

    Lascaux, A. S., F. Bouscarat, V. Descamps, E. Casalino, C. Picard-Dahan, B. Crickx, and S. Belaich. 1998. Cutaneous manifestations during disseminated trichosporonosis in an AIDS patient. Ann. Dermatol. Venereol. 125:111-113.

    Leaf, H. L., and M. S. Simberkoff. 1989. Invasive trichosporonosis in a patient with the acquired immunodeficiency syndrome. J. Infect. Dis. 160:356-357.

    Leone, G., L. Polonelli, L. M. Larocca, G. Morace, F. M. La Russa, and E. Pizzigallo. 1986. Recovery from disseminated Trichosporon beigelii (cutaneum) infection in a leukemia patient. J. Exp. Clin. Cancer Res. 5:89-92.

    Liu, K. L., R. Herbrecht, J. P. Bergerat, H. Koenig, J. Waller, and F. Oberling. 1990. Disseminated Trichosporon capitatum infection in a patient with acute leukaemia undergoing bone marrow transplantation. Bone Marrow Transplant. 6:219-221.

    Lopes, J. O., S. H. Alves, J. P. Benevenga, A. C. Rosa, and V. C. Gomez. 1994. Trichosporon beigelii peritonitis associated with continuous ambulatory peritoneal dialysis. Rev. Inst. Med. Trop. Sao Paulo 36:121-123.

    Lopes, J. O., S. H. Alves, C. Klock, L. T. Oliveira, and N. R. Dal Forno. 1997. Trichosporon inkin peritonitis during continuous ambulatory peritoneal dialysis with bibliography review. Mycopathologia 139:15-18.

    Lowenthal, R. M., K. Atkinson, D. R. Challis, R. G. Tucker, and J. C. Biggs. 1987. Invasive Trichosporon cutaneum infection: an increasing problem in immunosuppressed patients. Bone Marrow Transplant. 2:321-327.

    Madariaga, M. G., A. Tenorio, and L. Proia. 2003. Trichosporon inkin peritonitis treated with caspofungin. J. Clin. Microbiol. 41:5827-5829.

    Maples, H. D., C. D. Stowe, S. L. Saccente, and R. F. Jacobs. 2003. Voriconazole serum concentrations in an infant treated for Trichosporon beigelii infection. Pediatr. Infect. Dis. J. 22:1022-1024.

    Martino, P., M. Venditti, A. Micozzi, G. Morace, L. Polonelli, M. P. Mantovani, M. C. Petti, V. L. Burgio, C. Santini, P. Serra, and F. Mandelli. 1990. Blastoschizomyces capitatus: an emerging cause of invasive fungal disease in leukemia patients. Rev. Infect. Dis. 12:570-582.

    Martino, R., M. Salavert, R. Parody, J. F. Tomas, R. de la Camara, L. Vazquez, I. Jarque, E. Prieto, J. L. Sastre, I. Gadea, J. Peman, and J. Sierra. 2004. Blastoschizomyces capitatus infection in patients with leukemia: report of 26 cases. Clin. Infect. Dis. 38:335-341.

    Marty, F. M., D. H. Barouch, E. P. Coakley, and L. R. Baden. 2003. Disseminated trichosporonosis caused by Trichosporon loubieri. J. Clin. Microbiol. 41:5317-5320.

    Mathews, M. S., and S. Prabhakar. 1995. Chronic meningitis caused by Trichosporon beigelii in India. Mycoses 38:125-126.

    McWhinney, P. H., J. C. Madgwick, A. V. Hoffbrand, A. Bhamra, and C. C. Kibbler. 1992. Successful surgical management of septic arthritis due to Trichosporon beigelii in a patient with acute myeloid leukaemia. Scand. J. Infect. Dis. 24:245-247.

    Meyer, M. H., V. Letscher-Bru, J. Waller, P. Lutz, L. Marcellin, and R. Herbrecht. 2002. Chronic disseminated Trichosporon asahii infection in a leukemic child. Clin. Infect. Dis. 35:e22-e25.

    Miro, O., E. Sacanella, P. Nadal, M. M. Lluch, J. M. Nicolas, J. Milla, and A. Urbano-Marquez. 1994. Trichosporon beigelii fungemia and metastatic pneumonia in a trauma patient. Eur. J. Clin. Microbiol. Infect. Dis. 13:604-606.

    Mooty, M. Y., S. S. Kanj, M. Y. Obeid, G. Y. Hassan, and G. F. Araj. 2001. A case of Trichosporon beigelii endocarditis. Eur. J. Clin. Microbiol. Infect. Dis. 20:139-142.

    Moretti-Branchini, M. L., K. Fukushima, A. Z. Schreiber, K. Nishimura, P. M. Papaiordanou, P. Trabasso, R. Tanaka, and M. Miyaji. 2001. Trichosporon species infection in bone marrow transplanted patients. Diagn. Microbiol. Infect. Dis. 39:161-164.

    Morimoto, S., C. Shimazaki, H. Goto, Y. Hirata, T. Tasumi, N. Yamagata, T. Hirata, E. Ashihara, T. Inaba, and N. Fujita. 1994. Trichosporon cutaneum fungemia in patients with acute myeloblastic leukemia and measurement of serum D-arabinitol, Candida antigen (CAND-TEC), and beta-D-glucan. Ann. Hematol. 68:159-161.

    Moylett, E. H., J. Chinen, and W. T. Shearer. 2003. Trichosporon pullulans infection in 2 patients with chronic granulomatous diseases: an emerging pathogen and review of the literature. J. Allergy Clin. Immunol. 111:1370-1374.

    Muramatsu, H., H. Kume, M. Hojo, K. Iitaka, M. Okudaira, and H. Ohtani. 1992. A case of Trichosporon beigelii peritonitis in CAPD. Kansenshogaku Zasshi 66:1129-1132.

    Nahass, G. T., S. P. Rosenberg, C. L. Leonardi, and N. S. Penneys. 1993. Disseminated infection with Trichosporon beigelii. Report of a case and review of the cutaneous and histologic manifestations. Arch. Dermatol. 129:1020-1023.

    Nakagawa, T., K. Nakashima, T. Takaiwa, and K. Negayama. 2000. Trichosporon cutaneum (Trichosporon asahii) infection mimicking hand eczema in a patient with leukemia. J. Am. Acad. Dermatol. 42:929-931.

    Nesher, N., A. Erez, D. Nezer, R. Finkelstein, and Y. Barel. 1997. Acute fungal endocarditis due to Trichosporon beigelii. Harefuah 132:396-398.

    Ness, M. J., R. S. Markin, R. P. Wood, B. W. Shaw, Jr., and G. L. Woods. 1989. Disseminated Trichosporon beigelii infection after orthotopic liver transplantation. Am. J. Clin. Pathol. 92:119-123.

    Nettles, R. E., L. S. Nichols, K. Bell-McGuinn, M. R. Pipeling, P. J. Scheel, Jr., and W. G. Merz. 2003. Successful treatment of Trichosporon mucoides infection with fluconazole in a heart and kidney transplant recipient. Clin. Infect. Dis. 36:e63-e66.

    Oelz, O., A. Schaffner, P. Frick, and G. Schaer. 1983. Trichosporon capitatum: thrush-like oral infection, local invasion, fungaemia and metastatic abscess formation in a leukaemic patient. J. Infect. 6:183-185.

    Ogata, K., Y. Tanabe, K. Iwakiri, T. Ito, T. Yamada, K. Dan, and T. Nomura. 1990. Two cases of disseminated Trichosporon beigelii infection treated with combination antifungal therapy. Cancer 65:2793-2795.

    Ortiz, A. M., C. Sanz-Rodriguez, J. Culebras, B. Buendia, I. Gonzalez-Alvaro, E. Ocon, and R. de la Camara. 1998. Multiple spondylodiscitis caused by Blastoschizomyces capitatus in an allogeneic bone marrow transplantation recipient. J. Rheumatol. 25:2276-2278.

    Padhye, A. A., S. Verghese, P. Ravichandran, G. Balamurugan, L. Hall, P. Padmaja, and M. C. Fernandez. 2003. Trichosporon loubieri infection in a patient with adult polycystic kidney disease. J. Clin. Microbiol. 41:479-482.

    Pagano, L., G. Morace, E. Ortu-La Barbera, M. Sanguinetti, and G. Leone. 1996. Adjuvant therapy with rhGM-CSF for the treatment of Blastoschizomyces capitatus systemic infection in a patient with acute myeloid leukemia. Ann. Hematol. 73:33-34.

    Panagopoulou, P., J. Evdoridou, E. Bibashi, J. Filioti, D. Sofianou, G. Kremenopoulos, and E. Roilides. 2002. Trichosporon asahii: an unusual cause of invasive infection in neonates. Pediatr. Infect. Dis. J. 21:169-170.

    Paphitou, N. I., L. Ostrosky-Zeichner, V. L. Paetznick, J. R. Rodriguez, E. Chen, and J. H. Rex. 2002. In vitro antifungal susceptibilities of Trichosporon species. Antimicrob. Agents Chemother. 46:1144-1146.

    Paz, I., L. Barbeyto, A. Tinajas, J. L. Sastre, and J. L. Rodriguez-Tuleda. 2000. Blastoschizomyces capitatus fungemia in a neutropenic patient. Enferm. Infecc. Microbiol. Clin. 18:291-292.

    Perez-Sanchez, I., J. Anguita, P. Martin-Rabadan, P. Munoz, D. Serrano, A. Escudero, and T. Pintado. 2000. Blastoschizomyces capitatus infection in acute leukemia patients. Leuk. Lymphoma 39:209-212.

    Pfaller, M. A. 1994. Epidemiology and control of fungal infections. Clin. Infect. Dis. 19(Suppl. 1):S8-S13.

    Pierard, G. E., D. Read, C. Pierard-Franchimont, Y. Lother, A. Rurangirwa, and J. Arrese Estrada. 1992. Cutaneous manifestations in systemic trichosporonosis. Clin. Exp. Dermatol. 17:79-88.

    Piwoz, J. A., G. J. Stadtmauer, E. J. Bottone, I. Weitzman, E. Shlasko, and C. Cummingham-Rundles. 2000. Trichosporon inkin lung abscesses presenting as a penetrating chest wall mass. Pediatr. Infect. Dis. J. 19:1025-1027.

    Salkin, I. F., M. A. Gordon, W. A. Samsonoff, and C. L. Rieder. 1985. Blastoschizomyces capitatus, a new combination. Mycotaxon 22:375-380.

    Sanz, M. A., F. Lopez, M. L. Martinez, G. F. Sanz, J. A. Martinez, G. Martin, and M. Gobernado. 1996. Disseminated Blastoschizomyces capitatus infection in acute myeloblastic leukaemia. Report of three cases. Support Care Cancer 4:291-293.

    Saral, R. 1991. Candida and Aspergillus infections in immunocompromised patients: an overview. Rev. Infect. Dis. 13:487-492.

    Schiemann, R., A. Glasmacher, E. Bailly, R. Horre, E. Molitor, C. Leutner, M. T. Smith, R. Kleinschmidt, G. Marklein, and T. Sauerbruch. 1998. Geotrichum capitatum septicaemia in neutropenic patients: case report and review of the literature. Mycoses 41:113-116.

    Shigehara, K., K. Takahashi, K. Tsunematsu, H. Koba, S. Katoh, M. Asakawa, and A. Suzuki. 1991. A case of Trichosporon pullulans infection of the lung with adult T-cell leukaemia. Jpn. J. Med. 30:135-137.

    Smith, M. T., and G. A. Poot. 1998. Dipodascus capitatus, Dipodascus spicifer and Geotrichum clavatum: genomic characterization. Antonie Leeuwenhoek 74:229-235.

    Spanik, S., T. Kollar, J. Gyarfas, A. Kunova, and V. Krcmery. 1995. Successful treatment of catheter-associated fungemia due to Candida krusei and Trichosporon beigelii in a leukemic patient receiving prophylactic itraconazole. Eur. J. Clin. Microbiol. Infect. Dis. 14:148-149.

    Still, J. M., K. Orlet, and E. J. Law. 1994. Trichosporon beigelii septicaemia in a burn patient. Burns 20:467-468.

    Sugita, T., A. Nishikawa, T. Shinoda, and H. Kume. 1995. Taxonomic position of deep-seated, mucosa-associated, and superficial isolates of Trichosporon cutaneum from trichosporonosis patients. J. Clin. Microbiol. 33:1368-1370.

    Sugita, T., A. Nishikawa, and T. Shinoda. 1998. Identification of Trichosporon asahii by PCR based on sequences of the internal transcribed spacer regions. J. Clin. Microbiol. 36:2742-2744.

    Sugita, T., A. Nishikawa, R. Ikeda, and T. Shinoda. 1999. Identification of medically relevant Trichosporon species based on sequences of internal transcribed spacer regions and construction of a database for Trichosporon identification. J. Clin. Microbiol. 37:1985-1993.

    Surmont, I., B. Vergauwen, L. Marcelis, L. Verbist, G. Verhoef, and M. Boogaerts. 1990. First report of chronic meningitis caused by Trichosporon beigelii. Eur. J. Clin. Microbiol. Infect. Dis. 9:226-229.

    Takamura, S., T. Oono, H. Kanzaki, and J. Arata. 1999. Disseminated trichosporonosis with Trichosporon asahii. Eur. J. Dermatol. 9:577-579.

    Tashiro, T., H. Nagai, P. Kamberi, Y. Goto, H. Kikuchi, M. Nasu, and S. Akizuki. 1994. Disseminated Trichosporon beigelii infection in patients with malignant diseases: immunohistochemical study and review. Eur. J. Clin. Microbiol. Infect. Dis. 13:218-224.

    Tashiro, T., H. Nagai, H. Nagaoka, Y. Goto, P. Kamberi, and M. Nasu. 1995. Trichosporon beigelii pneumonia in patients with hematologic malignancies. Chest 108:190-195.

    Tashiro, T., H. Nagai, T. Yamasaki, Y. Goto, S. Akizuki, and M. Nasu. 1993. Disseminated Trichosporon beigelii infection: report of nine cases and review. Kansenshogaku Zasshi 67:704-711.

    Tawara, S., F. Ikeda, K. Maki, Y. Morishita, K. Otomo, N. Teratani, T. Goto, M. Tomishima, H. Ohki, A. Yamada, K. Kawabata, H. Takasugi, K. Sakane, H. Tanaka, F. Matsumo, and S. Kubahara. 2000. In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi. Antimicrob. Agents Chemother. 44:57-62.

    Uzun, O., S. Kocagoz, Y. Centikaya, S. Arikan, and S. Unal. 1997. In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates. Antimicrob. Agents Chemother. 41:1156-1157.

    Vasta, S., M. Menozzi, R. Scime, A. Indovina, A. Speciale, G. Liberti, C. Spano, and I. Majolino. 1993. Central catheter infection by Trichosporon beigelii after autologous blood stem cell transplantation. A case report and review of the literature. Haematologica 78:64-67.

    Venditti, M., B. Posteraro, G. Morace, and P. Martino. 1991. In vitro comparative activity of fluconazole and other antifungal agents against Blastoschizomyces capitatus. J. Chemother. 3:13-15.

    Viscoli, C., C. Girmenia, A. Marinus, L. Collette, P. Martino, B. Lebeau, D. Spence, V. Krcmery, B. De Pauw, and F. Meunier. 1999. Candidemia in cancer patients. A prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin. Infect. Dis. 28:1071-1079.

    Walsh, T. J., J. W. Lee, G. P. Melcher, E. Navarro, J. Bacher, D. Callender, K. D. Reed, T. Wu, G. Lopez-Berestein, and P. A. Pizzo. 1992. Experimental Trichosporon infection in persistently granulocytopenic rabbits: implications for pathogenesis, diagnosis, and treatment of an emerging opportunistic mycosis. J. Infect. Dis. 166:121-133.

    Walsh, T. J., G. P. Melcher, M. G. Rinaldi, J. Lecciones, D. A. McGough, P. Kelly, J. Lee, D. Callender, M. Rubin, and P. A. Pizzo. 1990. Trichosporon beigelii, an emerging pathogen resistant to amphotericin B. J. Clin. Microbiol. 28:1616-1622.

    Walsh, T. J., K. R. Newman, M. Moody, R. C. Wharton, and J. C. Wade. 1986. Trichosporonosis in patients with neoplastic disease. Medicine 65:268-279.

    Wang, H. Y., and J. L. Lin. 1999. Trichosporon beigelii fungaemia in a patient with haemodialysis. Nephrol. Dial. Transplant. 14:2017-2018.

    Watson, K. C., and S. Kallichurum. 1970. Brain abscess due to Trichosporon cutaneum. J. Med. Microbiol. 3:191-193.

    Wolf, D. G., R. Falk, M. Hacham, B. Theelen, T. Boekhout, G. Scorzetti, M. Shapiro, C. Block, I. F. Salkin, and I. Polacheck. 2001. Multidrug-resistant Trichosporon asahii infection of nongranulocytopenic patients in three intensive care units. J. Clin. Microbiol. 39:4420-4425.

    Yildiran, A., S. Kucukoduk, A. Sanic, N. Belet, and A. Guvenli. 2003. Disseminated Trichosporon asahii infection in a preterm. Am. J. Perinatol. 20:269-271.

    Yoshihara, T., K. Mori, Y. Nishimura, H. Ishida, A. Morimoto, and S. Imashuku. 2004. Osteocartilagineous involvement in Blastoschizomyces capitatus (Trichosporon capitatum) infection in a bone marrow transplant recipient. Br. J. Haematol. 124:405.

    Yoss, B. S., R. L. Sautter, and H. J. Brenker. 1997. Trichosporon beigelii, a new neonatal pathogen. Am. J. Perinatol. 14:113-117.


医学百科App—医学基础知识学习工具


页:
返回顶部】【打印本文】【放入收藏夹】【收藏到新浪】【发布评论



察看关于《Invasive Infections Caused by Trichosporon Species and Geotrichum capitatum in Patients with Hematological Malignancies: a Retrospective Multicenter Study fro》的讨论


关闭

网站地图 | RSS订阅 | 图文 | 版权说明 | 友情链接
Copyright © 2008 39kf.com All rights reserved. 医源世界 版权所有
医源世界所刊载之内容一般仅用于教育目的。您从医源世界获取的信息不得直接用于诊断、治疗疾病或应对您的健康问题。如果您怀疑自己有健康问题,请直接咨询您的保健医生。医源世界、作者、编辑都将不负任何责任和义务。
本站内容来源于网络,转载仅为传播信息促进医药行业发展,如果我们的行为侵犯了您的权益,请及时与我们联系我们将在收到通知后妥善处理该部分内容
联系Email: