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Sample records for acute invasive fungal

  1. Invasive Fungal Infections in Acute Leukemia

    PubMed Central

    Bhatt, Vijaya R.; Viola, George M.; Ferrajoli, Alessandra

    2011-01-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed. PMID:23556092

  2. Invasive fungal infections in acute leukemia.

    PubMed

    Bhatt, Vijaya R; Viola, George M; Ferrajoli, Alessandra

    2011-08-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed.

  3. Minireview: Invasive fungal infection complicating acute Plasmodium falciparum malaria.

    PubMed

    Däbritz, Jan; Schneider, Markward; Just-Nuebling, Gudrun; Groll, Andreas H

    2011-07-01

    Malaria is the most important parasitic infection in people, affecting 5-10% of the world's population with more than two million deaths a year. Whereas invasive bacterial infections are not uncommon during severe Plasmodium falciparum malaria, only a few cases of opportunistic fungal infections have been reported. Here, we present a fatal case of disseminated hyalohyphomycosis associated with acute P. falciparum malaria in a non-immune traveller, review the cases reported in the literature and discuss the theoretical foundations for the increased susceptibility of non-immune individuals with severe P. falciparum malaria to opportunistic fungal infections. Apart from the availability of free iron as sequelae of massive haemolysis, tissue damage, acidosis and measures of advanced life support, patients with complicated P. falciparum malaria also are profoundly immunosuppressed by the organism's interaction with innate and adaptive host immune mechanisms.

  4. Serum posaconazole levels during acute myeloid leukaemia induction therapy: correlations with breakthrough invasive fungal infections.

    PubMed

    Cattaneo, Chiara; Panzali, Annafranca; Passi, Angela; Borlenghi, Erika; Lamorgese, Cinzia; Petullà, Marta; Re, Alessandro; Caimi, Luigi; Rossi, Giuseppe

    2015-06-01

    The usefulness of posaconazole therapeutic drug monitoring (TDM) is still a matter of debate. A correlation between posaconazole serum levels and breakthrough invasive fungal infections (IFI) has not been clearly demonstrated so far. We analysed posaconazole serum levels in patients with acute myeloid leukaemia (AML) during induction therapy and correlated them with the incidence of breakthrough IFI and the need of systemic antifungal therapy. Overall, 77 AML patients receiving posaconazole were evaluated for serum levels; breakthrough IFI were observed in five with at least one posaconazole TDM (6.5%). Median serum level was 534 ng ml(-1) (IQ range: 298.5-750.5 ng ml(-1) ) and did not change significantly over time. Four of the 40 patients with median posaconazole levels <500 ng ml(-1) developed IFI, as compared with only 1 of the 37 patients with median levels ≥500 (10% vs. 2.7%, P = 0.19). Median posaconazole levels on day 7 were 384.5 ng ml(-1) (IQ range: 207-659 ng ml(-1) ) and 560.5 ng ml(-1) (IQ range: 395-756 ng ml(-1) ) in patients requiring or not systemic antifungal treatment respectively (P = 0.067). These results seem to confirm that higher median serum levels of posaconazole correlate with higher prophylactic efficacy against proven/probable IFI and with lesser need of systemic antifungal therapy.

  5. Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy

    PubMed Central

    Tüfekçi, Özlem; Yılmaz Bengoa, Şebnem; Demir Yenigürbüz, Fatma; Şimşek, Erdem; Karapınar, Tuba Hilkay; İrken, Gülersu; Ören, Hale

    2015-01-01

    Objective: Rapid and effective treatment of invasive fungal infection (IFI) in patients with leukemia is important for survival. In this study, we aimed to describe variations regarding clinical features, treatment modalities, time of restarting chemotherapy, and outcome in children with IFI and acute leukemia (AL). Materials and Methods: The charts of all pediatric AL patients in our clinic between the years of 2001 and 2013 were retrospectively reviewed. All patients received prophylactic fluconazole during the chemotherapy period. Results: IFI was identified in 25 (14%) of 174 AL patients. Most of them were in the consolidation phase of chemotherapy and the patients had severe neutropenia. The median time between leukemia diagnosis and definition of IFI was 122 days. Twenty-four patients had pulmonary IFI. The most frequent finding on computed tomography was typical parenchymal nodules. The episodes were defined as proven in 4 (16%) patients, probable in 7 (28%) patients, and possible in 14 (56%) patients. The median time for discontinuation of chemotherapy was 27 days. IFI was treated successfully in all patients with voriconazole, amphotericin B, caspofungin, or posaconazole alone or in combination. Chemotherapy was restarted in 50% of the patients safely within 4 weeks and none of those patients experienced reactivation of IFI. All of them were given secondary prophylaxis. The median time for antifungal treatment and for secondary prophylaxis was 26 and 90 days, respectively. None of the patients died due to IFI. Conclusion: Our data show that rapid and effective antifungal therapy with rational treatment modalities may decrease the incidence of death and that restarting chemotherapy within several weeks may be safe in children with AL and IFI. PMID:25913290

  6. [Emerging invasive fungal infections].

    PubMed

    Alvez, F; Figueras, C; Roselló, E

    2010-07-01

    The frequency and diversity of invasive fungal infections has changed over the last 25 years. The emergence of less common, but medically important fungi has increased, and the children at risk has expanded, with the inclusion of medical conditions such as cancer, mainly haematological malignancy or stem cell transplant, immunosuppressive therapy, prolonged neutropenia, and T-cell immunodeficiency. Among mould infections, fusariosis and phaeohyphomycosis (Dematiaceous fungi) have been increasingly reported in this group of patients. To successfully manage these challenging infections, it is imperative that paediatricians and sub-specialists remain aware of the optimal and timely diagnosis and therapeutic options. Unlike other common mycoses that cause human disease, there no simple antigen or serological tests available to detect these pathogens in tissue or blood. The outcome for these disseminate, and often refractory fungal infections in neutropenic patients and transplant recipients remains extremely poor, requiring early and aggressive therapy. Unfortunately there are no guidelines outlining the choices for optimal therapy in the treatment of paediatric invasive fungal infections do not exist, and on the other hand are limited paediatric data available comparing antifungal agents in children with proven, probable or suspected invasive fungal infection. The options for treatment rest mainly on some adult guidelines that comment on the treatment of these emerging and uncommon important fungi in children. Despite the sparse clinical trials available on treatment and its poor outcome, options for treatment of invasive fungal infections have increased with the advance of new antifungal agents, with improved tolerability and increased range of activity. The epidemiology, clinical manifestations, diagnosis and treatment of fusariosis and phaeohyphomycosis are discussed in this article.

  7. Chapter 8: Invasive fungal rhinosinusitis.

    PubMed

    Duggal, Praveen; Wise, Sarah K

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in the acute fulminant form. Early symptoms can often mimic rhinosinusitis, while late symptoms can cause significant morbidity and mortality. Swelling and mucosal thickening can quickly progress to pale or necrotic tissue in the nasal cavity and sinuses, and the disease can rapidly spread and invade the palate, orbit, cavernous sinus, cranial nerves, skull base, carotid artery, and brain. IFRS can be life threatening if left undiagnosed or untreated. While the acute fulminant form of IFRS is the most rapidly progressive and destructive, granulomatous and chronic forms also exist. Diagnosis of IFRS often mandates imaging studies in conjunction with clinical, endoscopic, and histopathological examination. Treatment of IFRS consists of reversing the underlying immunosuppression, antifungal therapy, and aggressive surgical debridement. With early diagnosis and treatment, IFRS can be treated and increase patient survival.

  8. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study)

    PubMed Central

    Caira, Morena; Candoni, Anna; Verga, Luisa; Busca, Alessandro; Delia, Mario; Nosari, Annamaria; Caramatti, Cecilia; Castagnola, Carlo; Cattaneo, Chiara; Fanci, Rosa; Chierichini, Anna; Melillo, Lorella; Mitra, Maria Enza; Picardi, Marco; Potenza, Leonardo; Salutari, Prassede; Vianelli, Nicola; Facchini, Luca; Cesarini, Monica; De Paolis, Maria Rosaria; Di Blasi, Roberta; Farina, Francesca; Venditti, Adriano; Ferrari, Antonella; Garzia, Mariagrazia; Gasbarrino, Cristina; Invernizzi, Rosangela; Lessi, Federica; Manna, Annunziata; Martino, Bruno; Nadali, Gianpaolo; Offidani, Massimo; Paris, Laura; Pavone, Vincenzo; Rossi, Giuseppe; Spadea, Antonio; Specchia, Giorgina; Trecarichi, Enrico Maria; Vacca, Adriana; Cesaro, Simone; Perriello, Vincenzo; Aversa, Franco; Tumbarello, Mario; Pagano, Livio

    2015-01-01

    Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient’s risk category and improve targeted prophylactic

  10. Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study).

    PubMed

    Caira, Morena; Candoni, Anna; Verga, Luisa; Busca, Alessandro; Delia, Mario; Nosari, Annamaria; Caramatti, Cecilia; Castagnola, Carlo; Cattaneo, Chiara; Fanci, Rosa; Chierichini, Anna; Melillo, Lorella; Mitra, Maria Enza; Picardi, Marco; Potenza, Leonardo; Salutari, Prassede; Vianelli, Nicola; Facchini, Luca; Cesarini, Monica; De Paolis, Maria Rosaria; Di Blasi, Roberta; Farina, Francesca; Venditti, Adriano; Ferrari, Antonella; Garzia, Mariagrazia; Gasbarrino, Cristina; Invernizzi, Rosangela; Lessi, Federica; Manna, Annunziata; Martino, Bruno; Nadali, Gianpaolo; Offidani, Massimo; Paris, Laura; Pavone, Vincenzo; Rossi, Giuseppe; Spadea, Antonio; Specchia, Giorgina; Trecarichi, Enrico Maria; Vacca, Adriana; Cesaro, Simone; Perriello, Vincenzo; Aversa, Franco; Tumbarello, Mario; Pagano, Livio

    2015-02-01

    Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient's risk category and improve targeted prophylactic

  11. Empirical caspofungin therapy in clinical practice for suspected invasive fungal disease in adults with acute lymphoblastic leukaemia.

    PubMed

    Kiehl, Michael G; Egerer, Gerlinde; Engelhardt, Monika; Gross, Barbara

    2015-02-01

    Patients with acute lymphoblastic leukaemia (ALL) after cytotoxic chemotherapy or haematopoietic stem cell transplantation (HSCT) are at risk for life-threatening invasive fungal disease (IFD). The aim was to evaluate the characteristics, antifungal therapy and outcome of adult patients with ALL after chemotherapy or HSCT receiving caspofungin empirically in a clinical setting. Retrospective chart reviews were conducted at nine large tertiary care centres in Germany. Adult patients with ALL treated empirically with caspofungin according to the product label between 2006 and 2012 were eligible. Data were extracted as case reports. In total, 25 patients (12 males, 13 females; median age 37 years; 19 with B-ALL, 6 with T-ALL) with 28 treatment episodes because of suspected IFD (18 episodes after chemotherapy, 10 episodes after allogeneic HSCT) were included in the analysis. Empirical caspofungin therapy (median duration: 19 days, range 1-105 days) was given as first-line monotherapy in 20 (71.4%), second-line monotherapy in five (17.9%) and combination therapy in three (10.7%) episodes respectively. Therapy rated successful according to the physician's overall assessment (inflammatory parameters, clinical symptoms): 20 (95%) of 21 evaluable episodes with therapy duration of at least 8 days. Empirical caspofungin appears to be an effective therapeutic option in critically ill adult ALL patients with suspected IFD in clinical practice.

  12. [Iron and invasive fungal infection].

    PubMed

    Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María

    2013-01-01

    Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis.

  13. The population biology of fungal invasions.

    PubMed

    Gladieux, P; Feurtey, A; Hood, M E; Snirc, A; Clavel, J; Dutech, C; Roy, M; Giraud, T

    2015-05-01

    Fungal invasions are increasingly recognized as a significant component of global changes, threatening ecosystem health and damaging food production. Invasive fungi also provide excellent models to evaluate the generality of results based on other eukaryotes. We first consider here the reasons why fungal invasions have long been overlooked: they tend to be inconspicuous, and inappropriate methods have been used for species recognition. We then review the information available on the patterns and mechanisms of fungal invasions. We examine the biological features underlying invasion success of certain fungal species. We review population structure analyses, revealing native source populations and strengths of bottlenecks. We highlight the documented ecological and evolutionary changes in invaded regions, including adaptation to temperature, increased virulence, hybridization, shifts to clonality and association with novel hosts. We discuss how the huge census size of most fungi allows adaptation even in bottlenecked, clonal invaders. We also present new analyses of the invasion of the anther-smut pathogen on white campion in North America, as a case study illustrating how an accurate knowledge of species limits and phylogeography of fungal populations can be used to decipher the origin of invasions. This case study shows that successful invasions can occur even when life history traits are particularly unfavourable to long-distance dispersal and even with a strong bottleneck. We conclude that fungal invasions are valuable models to contribute to our view of biological invasions, in particular by providing insights into the traits as well as ecological and evolutionary processes allowing successful introductions.

  14. Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy☆,☆☆,★,★★

    PubMed Central

    Neofytos, Dionissios; Lu, Kit; Hatfield-Seung, Amy; Blackford, Amanda; Marr, Kieren A.; Treadway, Suzanne; Ostrander, Darin; Nussenblatt, Veronique; Karp, Judith

    2014-01-01

    This is a retrospective, single-center study of adult patients with newly diagnosed acute myelogenous leukemia (AML), who received intensive induction timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%) patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%) probable, and 103 (95.4%) were possible, using current definitions. Overall, 6-month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and without an IFI, respectively. Older age (≥50 years; hazard ratio [HR]: 2.5, P < 0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We report relatively low rates of IC despite lack of routine primary antifungal prophylaxis, albeit associated with poor long-term survival. High rates of IMI, the vast majority with a possible diagnosis, were observed. Host-related variables (demographics and baseline organ dysfunction) were identified as the most significant risk factors for IFI and mortality predictors in this series. PMID:23142166

  15. High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan

    PubMed Central

    Kung, Hsiang-Chi; Yao, Ming; Wu, Un-In; Hsu, Szu-Chun; Lin, Chien-Ting; Li, Chi-Cheng; Wu, Shang-Ju; Hou, Hsin-An; Chou, Wen-Chien; Huang, Shang-Yi; Tsay, Woei; Chen, Yao-Chang; Chen, Yee-Chun; Chang, Shan-Chwen; Ko, Bor-Sheng; Tien, Hwei-Fang

    2015-01-01

    Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100–2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided. PMID:26061179

  16. Treatment cost of invasive fungal disease (Ifd) in patients with acute myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German hospitals.

    PubMed

    Rieger, C T; Cornely, O A; Hoppe-Tichy, T; Kiehl, M; Knoth, H; Thalheimer, M; Schuler, U; Ullmann, A J; Ehlken, B; Ostermann, H

    2012-11-01

    Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51,517 in the IFD group and €30,454 in the control group. Incremental costs of €21,063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.

  17. Combinatorial strategies for combating invasive fungal infections.

    PubMed

    Spitzer, Michaela; Robbins, Nicole; Wright, Gerard D

    2017-02-17

    Invasive fungal infections are an important cause of human mortality and morbidity, particularly for immunocompromised populations. However, there remains a paucity of antifungal drug treatments available to combat these fungal pathogens. Further, antifungal compounds are plagued with problems such as host toxicity, fungistatic activity, and the emergence of drug resistance in pathogen populations. A promising therapeutic strategy to increase drug effectiveness and mitigate the emergence of drug resistance is through the use of combination drug therapy. In this review we describe the current arsenal of antifungals in medicine and elaborate on the benefits of combination therapy to expand our current antifungal drug repertoire. We examine those antifungal combinations that have shown potential against fungal pathogens and discuss strategies being employed to discover novel combination therapeutics, in particular combining antifungal agents with non-antifungal bioactive compounds. The findings summarized in this review highlight the promise of combinatorial strategies in combatting invasive mycoses.

  18. Invasive fungal infection caused by geotrichum capitatum in patients with acute lymphoblastic leukemia: a case study and literature review

    PubMed Central

    Gao, Guang-Xun; Tang, Hai-Long; Zhang, Xuan; Xin, Xiao-Li; Feng, Juan; Chen, Xie-Qun

    2015-01-01

    Geotrichum capitatum infection has a very low incidence rate with atypical clinical symptoms, making diagnosis difficult, and it has a poor prognosis. The incidence is even more rare in China. This paper reports the first case of infection caused by G. capitatum during bone marrow suppression after chemotherapy in a Chinese patient with acute lymphoblastic leukemia. In addition, it reports a systematic literature review of diagnosis and treatment. The patient with acute lymphoblastic leukemia was confirmed to be infected with G. capitatum, involving lung, liver and skin, through a blood culture test. Caspofungin, amphotericin B loposome, and a combination therapy of amphotericin B liposome and voriconazole were used in succession for treatment. Despite normal body temperature and a slight improvement of clinical symptoms with the combination therapy treatment, the patient died 40 days after chemotherapy due to heart and lung failure. PMID:26550401

  19. Chronic invasive fungal sinusitis associated with intranasal drug use.

    PubMed

    Pekala, Kelly R; Clavenna, Matthew J; Shockley, Ross; Weiss, Vivian L; Turner, Justin H

    2015-12-01

    Chronic invasive fungal sinusitis (CIFS) is a rare but potentially aggressive form of invasive fungal disease that occurs in immunocompetent patients. We report a case of CIFS in an otherwise healthy young adult associated with intranasal illicit drug abuse. The patient presented with nonhealing nasal septal and palatal perforations. Biopsy demonstrated invasive Aspergillus flavus requiring surgical debridement and extended intravenous antifungal therapy. Tissue necrosis and ulceration related to intranasal drug use should be recognized as a potential risk factor for invasive fungal sinusitis.

  20. Nasal eschar: a warning sign of potentially fatal invasive fungal sinusitis in immunocompromised children.

    PubMed

    Idris, Nurliza; Lim, Lynne H Y

    2012-05-01

    Most invasive fungal sinusitis occurs in immunocompromised adult patients. We present the case study of a 12-year-old boy diagnosed with acute myeloblastic leukemia undergoing chemotherapy. He developed a progressive darkening discoloration over the dorsum of the nose that turned into an eschar. Nasal endoscopy revealed extensive necrotic tissue in the nasal cavity mucosa, inferior and middle turbinates, and septal cartilage that extended to the eschar of the skin over the nasal dorsum. Histopathology showed aspergillus invasive fungal rhinosinusitis.

  1. Combat-Related Invasive Fungal Wound Infections

    PubMed Central

    Rodriguez, Carlos J.

    2014-01-01

    Combat-related invasive fungal (mold) wound infections (IFIs) have emerged as an important and morbid complication following explosive blast injuries among military personnel. Similar to trauma-associated IFI cases among civilian populations, as in agricultural accidents and natural disasters, these infections occur in the setting of penetrating wounds contaminated by environmental debris. Specific risk factors for combat-related IFI include dismounted (patrolling on foot) blast injuries occurring mostly in southern Afghanistan, resulting in above knee amputations requiring resuscitation with large-volume blood transfusions. Diagnosis of IFI is based upon early identification of a recurrently necrotic wound following serial debridement and tissue-based histopathology examination with special stains to detect invasive disease. Fungal culture of affected tissue also provides supportive information. Aggressive surgical debridement of affected tissue is the primary therapy. Empiric antifungal therapy should be considered when there is a strong suspicion for IFI. Both liposomal amphotericin B and voriconazole should be considered initially for treatment since many of the cases involve not only Mucorales species but also Aspergillus or Fusarium spp., with narrowing of regimen based upon clinical mycology findings. PMID:25530825

  2. Posaconazole salvage treatment for invasive fungal infection.

    PubMed

    Kim, Jong Hun; Williams, Kali

    2014-10-01

    Invasive fungal infection (IFI) is an important cause of morbidity and mortality. Posaconazole is a second generation triazole with a broad spectrum, and it may be suitable for salvage antifungal treatment although posaconazole is not usually considered to be as first-line antifungal therapy for IFI. The purpose of this study was to assess the utility of posaconazole salvage treatment for IFI. We conducted a retrospective review of patients with salvage antifungal treatment with posaconazole for IFI at our institution between December 2007 and July 2012. A total of ten patients received posaconazole salvage IFI. Etiology of IFI was consisting of mucormycosis (four patients), Paecilomyces variotii (one patient), and unspecified IFI etiology (five patients). Causes of posaconazole treatment were following; intolerance of previous antifungal therapy in five patients, refractory IFI on previous antifungal therapy in four patients, and both intolerance of previous antifungal therapy and refractory IFI on previous antifungal therapy in one patient. Duration of posaconazole salvage treatment ranged from 15 to 355 days with median 47 days. The overall successful posaconazole salvage treatment response rate was 80.0 % (8 of 10 patients). There were three patients who died during the study period. However, only one death was attributed to the progression of IFI. Two patients discontinued posaconazole due to adverse events. Posaconazole salvage treatment was effective antifungal therapy for IFI. Further studies are needed to define the optimal therapeutic strategy.

  3. Invasive Fungal Infections after Natural Disasters

    PubMed Central

    Benedict, Kaitlin

    2014-01-01

    The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed. PMID:24565446

  4. Invasive fungal infections after natural disasters.

    PubMed

    Benedict, Kaitlin; Park, Benjamin J

    2014-03-01

    The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed.

  5. Invasive fungal infections in solid organ transplant recipients

    PubMed Central

    Shoham, Shmuel; Marr, Kieren A

    2014-01-01

    Invasive fungal infections are a major problem in solid organ transplant (SOT) recipients. Overall, the most common fungal infection in SOT is candidiasis, followed by aspergillosis and cryptococcosis, except in lung transplant recipients, where aspergillosis is most common. Development of invasive disease hinges on the interplay between host factors (e.g., integrity of anatomical barriers, innate and acquired immunity) and fungal factors (e.g., exposure, virulence and resistance to prophylaxis). In this article, we describe the epidemiology and clinical features of the most common fungal infections in organ transplantation. Within this context, we review recent advances in diagnostic modalities and antifungal chemotherapy, and their impact on evolving prophylaxis and treatment paradigms. PMID:22568718

  6. Management of invasive fungal infections: a role for polyenes.

    PubMed

    Chandrasekar, Pranatharthi

    2011-03-01

    The spectrum of invasive fungal infections (IFIs) continues to evolve with the emergence of rare and resistant fungal pathogens. Clinicians are faced with difficult diagnostic and treatment challenges in the management of immunocompromised patients at high risk of developing IFIs. Early and appropriate antifungal therapy is essential for a successful outcome when treating invasive mycoses. The armamentarium of antifungal drugs continues to grow; the three main classes of commonly administered drugs are the polyenes, azoles and echinocandins. The newer triazoles and the echinocandins have changed primary treatment options for some fungal infections, such as aspergillosis and candidiasis. However, despite their toxic potential, the oldest antifungal drugs, polyenes, remain useful in the treatment of IFIs because of their broad-spectrum activity, low rates of resistance and established clinical record, particularly in immunocompromised patients with breakthrough fungal infections. This review highlights important issues in the treatment of IFIs for consideration by clinicians.

  7. Invasive fungal disease in PICU: epidemiology and risk factors

    PubMed Central

    2012-01-01

    Candida and Aspergillus spp. are the most common agents responsible for invasive fungal infections in children. They are associated with a high mortality and morbidity rate as well as high health care costs. An important increase in their incidence has been observed during the past two decades. In infants and children, invasive candidiasis is five times more frequent than invasive aspergillosis. Candida sp. represents the third most common agent found in healthcare-associated bloodstream infections in children. Invasive aspergillosis is more often associated with hematological malignancies and solid tumors. Recommendations concerning prophylactic treatment for invasive aspergillosis have been recently published by the Infectious Diseases Society of America. Candida albicans is the main Candida sp. associated with invasive candidiasis in children, even if a strong trend toward the emergence of Candida non-albicans has been observed. The epidemiology and the risk factors for invasive fungal infections are quite different if considering previously healthy children hospitalized in the pediatric intensive care unit, or children with a malignancy or a severe hematological disease (leukemia). In children, the mortality rate for invasive aspergillosis is 2.5 to 3.5 higher than for invasive candidiasis (respectively 70% vs. 20% and 30%). PMID:22356683

  8. Invasive filamentous fungal infections associated with renal transplant tourism.

    PubMed

    Shoham, S; Hinestrosa, F; Moore, J; O'Donnell, S; Ruiz, M; Light, J

    2010-08-01

    'Transplant tourism,' the practice of traveling abroad to acquire an organ, has emerged as an issue in kidney transplantation. We treated a patient who developed invasive aspergillosis of the allograft vascular anastomosis after receiving a kidney transplant in Pakistan, prompting us to review the literature of invasive mycoses among commercial organ transplant recipients. We reviewed all published cases of infections in solid organ transplant recipients who bought their organs abroad and analyzed these reports for invasive fungal infections. Including the new case reported here, 19 cases of invasive fungal infections post commercial kidney transplant occurring in 17 patients were analyzed. Infecting organisms were Aspergillus species (12/19; 63%), Zygomycetes (5/19; 26%), and other fungi (2/19; 5%). Invasive mold infections were present at the transplanted graft in 6/17 patients (35%) with graft loss or death in 13/17 (76%) of patients and overall mortality (10/17) 59%. Invasive fungal infections, frequently originating at the graft site, have emerged as a devastating complication of commercial renal transplant and are associated with high rates of graft loss and death.

  9. Diagnosis of invasive fungal infections in immunocompromised children.

    PubMed

    Dornbusch, H J; Groll, A; Walsh, T J

    2010-09-01

    Early recognition and rapid initiation of effective treatment is a prerequisite for successful management of children with invasive fungal infections. The increasing diversity of fungal pathogens in high-risk patients, the differences in the antifungal spectra of available agents and the increasing rates of resistance call for identification of the infecting isolate at the species level and for information on drug resistance, in order to provide state-of-the-art patient care. Microscopy and culture of appropriate specimens remain the reference standard for mycological diagnosis, despite difficulties in obtaining appropriate and/or sufficient specimens, long durations of culture and false-negative results. Modern imaging studies and detection of circulating fungal cell wall components and DNA in blood and other body fluids or in affected tissues may improve the laboratory diagnosis of invasive mycoses.

  10. [General epidemiology of invasive fungal disease].

    PubMed

    Pemán, Javier; Salavert, Miguel

    2012-02-01

    Invasive mycoses associated with high morbidity and mortality rates are increasing among immunocompromised or severely ill patients. Candida, Cryptococcus, Pneumocystis and Aspergillus are most prevalent agents with varying distribution as regards geography, patient condition and hospital units. The latest multicentre candidaemia survey conducted in Spain, showed C. albicans as the most frequently isolated species followed by C. parapsilosis, C. glabrata, C. tropicalis and C. krusei in contrast with other European or American studies where C. glabrata was second in rank. Aspergillus spp. is the leading agent causing invasive mycoses among filamentous fungi followed by Fusarium spp., Scedosporium spp. and zygomycetes. Aspergillus fumigatus is the most common agent in invasive aspergillosis (and azole-resistant isolates have been reported) but in the last few years Aspergillus flavus, Aspergillus nidulans and Aspergillus terreus have been isolated with increasing frequency variable with geographical factors, patients' underlying conditions or previous antifungal treatments.

  11. Acute fungal sinusitis: natural history and the role of frozen section.

    PubMed

    Taxy, Jerome B; El-Zayaty, Shady; Langerman, Alexander

    2009-07-01

    Acute fungal sinusitis is a life-threatening infection affecting immunocompromised patients. Historically, the most commonly recovered fungi are Aspergillus and Mucor. The extent of potentially disfiguring debridement surgery is grossly determined by the appearance of bleeding at the margins, signifying viable tissue and the absence of fungus. Requests for frozen section may concern the initial diagnosis and the intraoperative verification of margin status. In 12 patients with acute fungal sinusitis, frozen section was used in 8. Routine H&E stains demonstrated fungal hyphae in necrotic debris in 5 cases, often associated with vascular and perineural invasion. All patients underwent extensive sinus debridement, including orbital exenteration in 2 cases. All 12 patients died, 9 of fungal sepsis. Autopsy in 3 patients showed pulmonary involvement (2 cases), intracranial spread (1 case), and no residual fungus (1 case). Inexperience with organism recognition is surmountable. Frozen section has a role in the management of this devastating disease.

  12. Recent advances in antifungal pharmacotherapy for invasive fungal infections.

    PubMed

    Gallagher, Jason C; MacDougall, Conan; Ashley, Elizabeth S Dodds; Perfect, John R

    2004-04-01

    Invasive fungal infections carry significant morbidity and mortality. Candida species have become one of the most frequent causes of bloodstream infections, and infections caused by molds such as Aspergillus are becoming more frequent in immunocompromised patients. As this population grows, more invasive fungal infections can be anticipated. In the past, treatment options have been limited for many of these infections due to toxicity and efficacy concerns with the available antifungals. Fortunately, the past few years have brought exciting developments in antifungal pharmacotherapy. Lipid-based formulations of amphotericin B were introduced in the 1990s to attenuate adverse effects caused by amphotericin B deoxycholate (Fungizone, Bristol-Myers Squibb). Most recently, the echinocandins have been added to our antifungal regimen with the introduction of caspofungin (Cancidas, Merck and Co.) and voriconazole (Vfend, Pfizer), a new triazole, has come to market. The introduction of the echinocandins has invigorated the discussion about combination antifungal therapy. Evidence-based studies using these new agents are accumulating, and they are assuming important roles in the pharmacotherapy of invasive fungal infections in seriously ill and complex patients.

  13. Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

    PubMed Central

    Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

    2014-01-01

    SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319

  14. Chronic Invasive Nongranulomatous Fungal Rhinosinusitis in Immunocompetent Individuals

    PubMed Central

    Turhan, Ozge; Ozbudak, Irem Hicran; Turhan, Murat

    2016-01-01

    Chronic invasive nongranulomatous fungal rhinosinusitis is a well-described but uncommon type of fungal rhinosinusitis (FRS). While the prevalence of chronic FRS is 0.11% in healthy individuals, only 1.3% of them are in nongranulomatous invasive nature. The majority of the cases in the literature have been reported from developing countries mostly located in the tropical regions, as typically occurring in the background of diabetes mellitus or corticosteroid treatment. The current paper reports four consecutive cases, who were diagnosed within a short period of six months at a single center of a country located outside the tropical climate zone. None of the patients had a comorbid disease that may cause immune suppression or a history of drug use. The only risk factor that may have a role in development of chronic invasive nongranulomatous FRS was that all of our patients were people working in greenhouse farming. Three cases underwent endoscopic sinus surgery, and one case underwent surgery with both endoscopic and external approaches. Systemic antifungal therapy was initiated in all cases in the postoperative period with voriconazole 200 mg orally twice a day. All patients achieved a complete clinical remission. Chronic invasive nongranulomatous FRS should be kept in mind in the presence of long-standing nonspecific sinonasal symptoms in immunocompetent individuals, particularly with a history of working in greenhouse farming. PMID:27703827

  15. Role of isavuconazole in the treatment of invasive fungal infections

    PubMed Central

    Wilson, Dustin T; Dimondi, V Paul; Johnson, Steven W; Jones, Travis M; Drew, Richard H

    2016-01-01

    Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug–drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation), and reduced drug–drug interactions (relative to voriconazole). Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of isavuconazole for invasive candidiasis (relative to comparator agents such as echinocandins) is not as robust. Therefore, isavuconazole use for invasive candidiasis may initially be reserved as a step-down oral option in those patients who cannot receive other azoles due to tolerability or spectrum of activity limitations. Post-marketing surveillance of isavuconazole will be important to better understand the safety and efficacy of this agent, as well as to better define the need for isavuconazole serum concentration monitoring

  16. Role of isavuconazole in the treatment of invasive fungal infections.

    PubMed

    Wilson, Dustin T; Dimondi, V Paul; Johnson, Steven W; Jones, Travis M; Drew, Richard H

    2016-01-01

    Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug-drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation), and reduced drug-drug interactions (relative to voriconazole). Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of isavuconazole for invasive candidiasis (relative to comparator agents such as echinocandins) is not as robust. Therefore, isavuconazole use for invasive candidiasis may initially be reserved as a step-down oral option in those patients who cannot receive other azoles due to tolerability or spectrum of activity limitations. Post-marketing surveillance of isavuconazole will be important to better understand the safety and efficacy of this agent, as well as to better define the need for isavuconazole serum concentration monitoring.

  17. Fungal invasion of normally non-phagocytic host cells.

    PubMed

    Filler, Scott G; Sheppard, Donald C

    2006-12-01

    Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

  18. Fungal Invasion of Normally Non-Phagocytic Host Cells

    PubMed Central

    Filler, Scott G; Sheppard, Donald C

    2006-01-01

    Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research. PMID:17196036

  19. Orbital Metastasis of Breast Cancer Mimicking Invasive Fungal Rhinosinusitis

    PubMed Central

    Hazboun, Igor Moreira; Sakuma, Emerson Taro Inoue; Sampaio, Marcelo Hamilton

    2016-01-01

    Introduction. A range of traumatic, vascular, inflammatory, infectious, and neoplastic processes can affect the orbit and its structures. In the area of otolaryngology, the rhino-orbital-cerebral involvement of invasive fungal rhinosinusitis can affect the orbit, which may look like initially a rhinosinusitis or even mimic malignancy. Case Presentation. Female patient, 32 years old, with headache and ocular proptosis. She was using prednisone in immunosuppressive doses for a year and had breast cancer treated three years earlier. The initial CT scan showed opacification of the sphenoid and ethmoid sinuses, left intraorbital involvement and contrast impregnation in the cavernous sinus. The biopsy resulted positive for invasive ductal carcinoma of the breast. Discussion. The initial CT scan of our patient showed both signs of early changes of invasive fungal rhinosinusitis (IFR) and possible metastatic involvement. The intracranial extension and ocular involvement are usually the most common signs of IFR (first hypothesis). Among metastases at the orbit and the eye, breast and lung carcinomas are the most frequent. Conclusion. Although several studies on the differential diagnosis of orbital lesions exist, especially when it concerns the involvement of the nasal cavity, the diagnosis by imaging is still a challenge. PMID:27563478

  20. Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia.

    PubMed

    Schmiedel, Yvonne; Zimmerli, Stephan

    2016-01-01

    Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of

  1. A Review of Diagnostic Methods for Invasive Fungal Diseases: Challenges and Perspectives.

    PubMed

    Falci, Diego R; Stadnik, Claudio M B; Pasqualotto, Alessandro C

    2017-03-29

    Invasive fungal diseases are associated with a high morbidity and mortality, particularly in the context of immunosuppression. Diagnosis of invasive fungal diseases is usually complicated by factors such as poor clinical suspicion and unspecific clinical findings. Access to modern diagnostic tools is frequently limited in developing countries. Here, we describe five real-life clinical cases from a Brazilian tertiary hospital, in order to illustrate how to best select diagnostic tests in patients with different fungal infections.

  2. Azole antifungals: 35 years of invasive fungal infection management.

    PubMed

    Allen, David; Wilson, Dustin; Drew, Richard; Perfect, John

    2015-06-01

    Prior to 1981, treatment options for invasive fungal infections were limited and associated with significant toxicities. The introduction of ketoconazole marked the beginning of an era of dramatic improvements over previous therapies for non-life-threatening mycosis. After nearly a decade of use, ketoconazole was quickly replaced by the triazoles fluconazole and itraconazole due to significant improvements in pharmacokinetic profile, spectrum of activity and safety. The triazoles posaconazole and voriconazole followed, and were better known for their further extended spectrum, specifically against emerging mold infections. With the exception of fluconazole, the triazoles have been plagued with significant inter- and intrapatient pharmacokinetic variability and all possess significant drug interactions. Azoles currently in development appear to combine an in vitro spectrum of activity comparable to voriconazole and posaconazole with more predictable pharmacokinetics and fewer adverse effects.

  3. Active invasion of bacteria into living fungal cells.

    PubMed

    Moebius, Nadine; Üzüm, Zerrin; Dijksterhuis, Jan; Lackner, Gerald; Hertweck, Christian

    2014-09-02

    The rice seedling blight fungus Rhizopus microsporus and its endosymbiont Burkholderia rhizoxinica form an unusual, highly specific alliance to produce the highly potent antimitotic phytotoxin rhizoxin. Yet, it has remained a riddle how bacteria invade the fungal cells. Genome mining for potential symbiosis factors and functional analyses revealed that a type 2 secretion system (T2SS) of the bacterial endosymbiont is required for the formation of the endosymbiosis. Comparative proteome analyses show that the T2SS releases chitinolytic enzymes (chitinase, chitosanase) and chitin-binding proteins. The genes responsible for chitinolytic proteins and T2SS components are highly expressed during infection. Through targeted gene knock-outs, sporulation assays and microscopic investigations we found that chitinase is essential for bacteria to enter hyphae. Unprecedented snapshots of the traceless bacterial intrusion were obtained using cryo-electron microscopy. Beyond unveiling the pivotal role of chitinolytic enzymes in the active invasion of a fungus by bacteria, these findings grant unprecedented insight into the fungal cell wall penetration and symbiosis formation.

  4. Active invasion of bacteria into living fungal cells

    PubMed Central

    Moebius, Nadine; Üzüm, Zerrin; Dijksterhuis, Jan; Lackner, Gerald; Hertweck, Christian

    2014-01-01

    The rice seedling blight fungus Rhizopus microsporus and its endosymbiont Burkholderia rhizoxinica form an unusual, highly specific alliance to produce the highly potent antimitotic phytotoxin rhizoxin. Yet, it has remained a riddle how bacteria invade the fungal cells. Genome mining for potential symbiosis factors and functional analyses revealed that a type 2 secretion system (T2SS) of the bacterial endosymbiont is required for the formation of the endosymbiosis. Comparative proteome analyses show that the T2SS releases chitinolytic enzymes (chitinase, chitosanase) and chitin-binding proteins. The genes responsible for chitinolytic proteins and T2SS components are highly expressed during infection. Through targeted gene knock-outs, sporulation assays and microscopic investigations we found that chitinase is essential for bacteria to enter hyphae. Unprecedented snapshots of the traceless bacterial intrusion were obtained using cryo-electron microscopy. Beyond unveiling the pivotal role of chitinolytic enzymes in the active invasion of a fungus by bacteria, these findings grant unprecedented insight into the fungal cell wall penetration and symbiosis formation. DOI: http://dx.doi.org/10.7554/eLife.03007.001 PMID:25182414

  5. Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

    PubMed

    Miyakoshi, Shigesaburo; Kusumi, Eiji; Matsumura, Tomoko; Hori, Akiko; Murashige, Naoko; Hamaki, Tamae; Yuji, Koichiro; Uchida, Naoyuki; Masuoka, Kazuhiro; Wake, Atsushi; Kanda, Yoshinobu; Kami, Masahiro; Tanaka, Yuji; Taniguchi, Shuichi

    2007-07-01

    Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.

  6. Update on epidemiology of and preventive strategies for invasive fungal infections in cancer patients.

    PubMed

    Perfect, John R; Hachem, Ray; Wingard, John R

    2014-11-15

    Changes in antineoplastic treatments and transplant practices are driving shifts in the epidemiology of invasive fungal diseases (IFDs). Patients with acute myelogenous leukemia (AML) and those undergoing bone marrow transplant (BMT) are at greatest risk for contracting IFDs. Unfortunately, there are few large population studies that can be used to track trends and help us to better understand why certain individuals within recognized high-risk groups are at greater risks than others for contracting IFDs. The growing use of antifungals in prophylaxis and treatment influences which species will cause an IFD as well as the resistance patterns of these fungi. On the one hand, antifungal prophylaxis has mitigated, but not eliminated, the threat of candidiasis. Furthermore, prophylaxis trials have shown trends of reduced aspergillosis in BMT patients; however, no survival benefits were seen, and 1 trial indicated a lower rate of aspergillosis and survival benefits in patients with AML. Future prophylaxis trials should reduce the heterogeneity of risk in study participants in order to better assess benefit; these trials should also incorporate fungal biomarkers into their design. The threat of emerging fungal resistance in prophylaxis strategies is real and must be monitored.

  7. Predicting Invasive Fungal Pathogens Using Invasive Pest Assemblages: Testing Model Predictions in a Virtual World

    PubMed Central

    Paini, Dean R.; Bianchi, Felix J. J. A.; Northfield, Tobin D.; De Barro, Paul J.

    2011-01-01

    Predicting future species invasions presents significant challenges to researchers and government agencies. Simply considering the vast number of potential species that could invade an area can be insurmountable. One method, recently suggested, which can analyse large datasets of invasive species simultaneously is that of a self organising map (SOM), a form of artificial neural network which can rank species by establishment likelihood. We used this method to analyse the worldwide distribution of 486 fungal pathogens and then validated the method by creating a virtual world of invasive species in which to test the SOM. This novel validation method allowed us to test SOM's ability to rank those species that can establish above those that can't. Overall, we found the SOM highly effective, having on average, a 96–98% success rate (depending on the virtual world parameters). We also found that regions with fewer species present (i.e. 1–10 species) were more difficult for the SOM to generate an accurately ranked list, with success rates varying from 100% correct down to 0% correct. However, we were able to combine the numbers of species present in a region with clustering patterns in the SOM, to further refine confidence in lists generated from these sparsely populated regions. We then used the results from the virtual world to determine confidences for lists generated from the fungal pathogen dataset. Specifically, for lists generated for Australia and its states and territories, the reliability scores were between 84–98%. We conclude that a SOM analysis is a reliable method for analysing a large dataset of potential invasive species and could be used by biosecurity agencies around the world resulting in a better overall assessment of invasion risk. PMID:22016773

  8. Invasive fungal sinusitis in a healthy athlete due to long-term anabolic steroid use.

    PubMed

    Kim, Irene A; Thompson, Christopher F; Kedeshian, Paul A; Palma-Diaz, Fernando; Suh, Jeffrey D

    2014-08-01

    Invasive fungal rhinosinusitis is a potentially fatal infection that affects immunocompromised patients. Prognosis is generally poor despite aggressive medical and surgical treatments. We present the first reported case of invasive fungal sinusitis in a healthy 18-year-old male athlete who was taking anabolic androgenic steroids (AAS). The effects of excessive AAS use on the immune system are not fully understood, but there may be consequences at supraphysiological concentrations. This case demonstrates potential immunomodulatory effects of anabolic steroids and highlights a previously unknown cause of invasive fungal sinusitis.

  9. Risk Factors Associated with Invasive Fungal Infections in Combat Trauma

    PubMed Central

    Rodriguez, Carlos J.; Weintrob, Amy C.; Shah, Jinesh; Malone, Debra; Dunne, James R.; Weisbrod, Allison B.; Lloyd, Bradley A.; Warkentien, Tyler E.; Murray, Clinton K.; Wilkins, Kenneth; Shaikh, Faraz; Carson, M. Leigh; Aggarwal, Deepak

    2014-01-01

    Abstract Background: In recent years, invasive fungal infections (IFI) have complicated the clinical course of patients with combat-related injuries. Commonalities in injury patterns and characteristics among patients with IFI led to the development of a Joint Trauma System (JTS) clinical practice guideline (CPG) for IFI management. We performed a case-control study to confirm and further delineate risk factors associated with IFI development in combat casualties with the objective of generating data to refine the CPG and promote timelier initiation of treatment. Methods: Data were collected retrospectively for United States (U.S.) military personnel injured during deployment in Afghanistan from June 2009 through August 2011. Cases were identified as IFI based upon wound cultures with fungal growth and/or fungal elements seen on histology, in addition to the presence of recurrent wound necrosis. Controls were matched using date of injury (±3 mo) and injury severity score (±10). Risk factor parameters analyzed included injury circumstances, blood transfusion requirements, amputations after first operative intervention, and associated injuries. Data are expressed as multivariate odds ratios (OR; 95% confidence interval [CI]). Results: Seventy-six IFI cases were identified from 1,133 U.S. military personnel wounded in Afghanistan and matched to 150 controls. Parameters associated significantly with the development of IFI multivariate analysis were blast injuries (OR: 5.7; CI: 1.1–29.6), dismounted at time of injury (OR: 8.5; CI: 1.2–59.8); above the knee amputations (OR: 4.1; CI: 1.3-12.7), and large-volume packed red blood cell (PRBC; >20 U) transfusions within first 24 h (OR: 7.0; CI: 2.5-19.7). Conclusions: Our analysis indicates that dismounted blast injuries, resulting in above the knee amputations, and requirement of large volume PRBC transfusions are independent predictors of IFI development. These data confirm all the preliminary risk factors, except for

  10. Epidemiology and identification of potential fungal pathogens causing invasive fungal infections in a tertiary care hospital in northeast Thailand.

    PubMed

    Faksri, Kiatichai; Kaewkes, Wanlop; Chaicumpar, Kunyaluk; Chaimanee, Prajuab; Wongwajana, Suwin

    2014-11-01

    Invasive fungal infections (IFIs) are life threatening and associated with a high mortality rate. Here, we describe the distribution of pathogens, host risk factors, and significance of fungi isolated from patients with IFIs. The study included 861 fungal isolates recovered between 2006 and 2011 from 802 patients at Srinagarind Hospital, Thailand. Based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group 2008 criteria, 28.5% (245/861 isolates) of the fungal isolates were considered to be causative agents of IFIs. The most common fungus was Candida albicans (46%, 396/861 isolates). However, the most common yeast causing IFIs was Cryptococcus neoformans (34.7%, 85/245 isolates), while the most common mould was Penicillium marneffei (10.6%, 26/245 isolates). Cryptococcosis was significantly associated with human immunodeficiency virus infections (P < 0.001). Trend analysis revealed that there was no significant increase in IFI cases (P = 0.34) from 2006 to 2011 or from 2007 to 2011 (P = 0.05), but there was a trend toward significant increases in candidiasis (P = 0.04). The fungal isolates were categorized according to the positive predictive value of their recovery in cultures as being true (>95%), moderate (5%-95%), and rare (<5%) pathogens. This classification system could facilitate the prediction of the likelihood of diseases caused by the isolated fungi.

  11. Alarmin(g) the innate immune system to invasive fungal infections.

    PubMed

    Caffrey, Alayna K; Obar, Joshua J

    2016-08-01

    Fungi encounter numerous stresses in a mammalian host, including the immune system, which they must adapt to in order to grow and cause disease. The host immune system tunes its response to the threat level posed by the invading pathogen. We discuss recent findings on how interleukin (IL)-1 signaling is central to tuning the immune response to the virulence potential of invasive fungi, as well as other pathogens. Moreover, we discuss fungal factors that may drive tissue invasion and destruction that regulate IL-1 cytokine release. Moving forward understanding the mechanisms of fungal adaption to the host, together with understanding how the host innate immune system recognizes invading fungal pathogens will increase our therapeutic options for treatment of invasive fungal infections.

  12. Improved outcomes associated with advances in therapy for invasive fungal infections in immunocompromised hosts.

    PubMed

    Metcalf, S C; Dockrell, D H

    2007-10-01

    Invasive fungal infections cause substantial morbidity and mortality in immunocompromised hosts. The response rate to therapy, in particular for invasive aspergillosis and invasive mould infections, has been poor. Recently a number of techniques to facilitate early diagnosis of these infections, in parallel with the development of a number of antifungals with increased potency and lower toxicity, have raised optimism that outcomes for invasive fungal infection can be improved upon. The availability of lipid formulations of amphotericin B, azoles with extended spectrum against filamentous fungi and the development of a new class of antifungal agents, the echinocandins, presents the clinician with a range of therapeutic choices. Recent clinical trials have provided important insights into how these agents should be used. In particular, voriconazole has demonstrated superior efficacy to amphotericin B in the management of invasive aspergillosis, posaconazole has been shown to have significant efficacy in the prophylaxis of invasive fungal infection in high-risk individuals and a role in salvage therapy of invasive aspergillosis, caspofungin has demonstrated efficacy in salvage therapy of invasive aspergillosis, and each of the echinocandins show activity without significant toxicity in invasive candidiasis. Nevertheless, many therapeutic areas of uncertainty remain, including the role of combination therapy, and will provide the focus for future studies.

  13. Optimizing Outcomes in Immunocompromised Hosts: Understanding the Role of Immunotherapy in Invasive Fungal Diseases

    PubMed Central

    Ravikumar, Sharada; Win, Mar Soe; Chai, Louis Yi Ann

    2015-01-01

    A major global concern is the emergence and spread of systemic life-threatening fungal infections in critically ill patients. The increase in invasive fungal infections, caused most commonly by Candida and Aspergillus species, occurs in patients with impaired defenses due to a number of reasons such as underlying disease, the use of chemotherapeutic and immunosuppressive agents, broad-spectrum antibiotics, prosthetic devices and grafts, burns, neutropenia and HIV infection. The high morbidity and mortality associated with these infections is compounded by the limited therapeutic options and the emergence of drug resistant fungi. Hence, creative approaches to bridge the significant gap in antifungal drug development needs to be explored. Here, we review the potential anti-fungal targets for patient-centered therapies and immune-enhancing strategies for the prevention and treatment of invasive fungal diseases. PMID:26635780

  14. Severe plant invasions can increase mycorrhizal fungal abundance and diversity.

    PubMed

    Lekberg, Ylva; Gibbons, Sean M; Rosendahl, Søren; Ramsey, Philip W

    2013-07-01

    Invasions by non-native plants can alter ecosystem functions and reduce native plant diversity, but relatively little is known about their effect on belowground microbial communities. We show that invasions by knapweed (Centaurea stoebe) and leafy spurge (Euphorbia esula, hereafter spurge)--but not cheatgrass (Bromus tectorum)--support a higher abundance and diversity of symbiotic arbuscular mycorrhizal fungi (AMF) than multi-species native plant communities. The higher AMF richness associated with knapweed and spurge is unlikely due to a co-invasion by AMF, because a separate sampling showed that individual native forbs hosted a similar AMF abundance and richness as exotic forbs. Native grasses associated with fewer AMF taxa, which could explain the reduced AMF richness in native, grass-dominated communities. The three invasive plant species harbored distinct AMF communities, and analyses of co-occurring native and invasive plants indicate that differences were partly driven by the invasive plants and were not the result of pre-invasion conditions. Our results suggest that invasions by mycotrophic plants that replace poorer hosts can increase AMF abundance and richness. The high AMF richness in monodominant plant invasions also indicates that the proposed positive relationship between above and belowground diversity is not always strong. Finally, the disparate responses among exotic plants and consistent results between grasses and forbs suggest that AMF respond more to plant functional group than plant provenance.

  15. Severe plant invasions can increase mycorrhizal fungal abundance and diversity

    PubMed Central

    Lekberg, Ylva; Gibbons, Sean M; Rosendahl, Søren; Ramsey, Philip W

    2013-01-01

    Invasions by non-native plants can alter ecosystem functions and reduce native plant diversity, but relatively little is known about their effect on belowground microbial communities. We show that invasions by knapweed (Centaurea stoebe) and leafy spurge (Euphorbia esula, hereafter spurge)—but not cheatgrass (Bromus tectorum)—support a higher abundance and diversity of symbiotic arbuscular mycorrhizal fungi (AMF) than multi-species native plant communities. The higher AMF richness associated with knapweed and spurge is unlikely due to a co-invasion by AMF, because a separate sampling showed that individual native forbs hosted a similar AMF abundance and richness as exotic forbs. Native grasses associated with fewer AMF taxa, which could explain the reduced AMF richness in native, grass-dominated communities. The three invasive plant species harbored distinct AMF communities, and analyses of co-occurring native and invasive plants indicate that differences were partly driven by the invasive plants and were not the result of pre-invasion conditions. Our results suggest that invasions by mycotrophic plants that replace poorer hosts can increase AMF abundance and richness. The high AMF richness in monodominant plant invasions also indicates that the proposed positive relationship between above and belowground diversity is not always strong. Finally, the disparate responses among exotic plants and consistent results between grasses and forbs suggest that AMF respond more to plant functional group than plant provenance. PMID:23486251

  16. Different degrees of plant invasion significantly affect the richness of the soil fungal community.

    PubMed

    Si, Chuncan; Liu, Xueyan; Wang, Congyan; Wang, Lei; Dai, Zhicong; Qi, Shanshan; Du, Daolin

    2013-01-01

    Several studies have shown that soil microorganisms play a key role in the success of plant invasion. Thus, ecologists have become increasingly interested in understanding the ecological effects of biological invasion on soil microbial communities given continuing increase in the effects of invasive plants on native ecosystems. This paper aims to provide a relatively complete depiction of the characteristics of soil microbial communities under different degrees of plant invasion. Rhizospheric soils of the notorious invasive plant Wedelia trilobata with different degrees of invasion (uninvaded, low-degree, and high-degree using its coverage in the invaded ecosystems) were collected from five discrete areas in Hainan Province, P. R. China. Soil physicochemical properties and community structure of soil microorganisms were assessed. Low degrees of W. trilobata invasion significantly increased soil pH values whereas high degrees of invasion did not significantly affected soil pH values. Moreover, the degree of W. trilobata invasion exerted significant effects on soil Ca concentration but did not significantly change other indices of soil physicochemical properties. Low and high degrees of W. trilobata invasion increased the richness of the soil fungal community but did not pose obvious effects on the soil bacterial community. W. trilobata invasion also exerted obvious effects on the community structure of soil microorganisms that take part in soil nitrogen cycling. These changes in soil physicochemical properties and community structure of soil microbial communities mediated by different degrees of W. trilobata invasion may present significant functions in further facilitating the invasion process.

  17. Different Degrees of Plant Invasion Significantly Affect the Richness of the Soil Fungal Community

    PubMed Central

    Si, Chuncan; Liu, Xueyan; Wang, Congyan; Wang, Lei; Dai, Zhicong; Qi, Shanshan; Du, Daolin

    2013-01-01

    Several studies have shown that soil microorganisms play a key role in the success of plant invasion. Thus, ecologists have become increasingly interested in understanding the ecological effects of biological invasion on soil microbial communities given continuing increase in the effects of invasive plants on native ecosystems. This paper aims to provide a relatively complete depiction of the characteristics of soil microbial communities under different degrees of plant invasion. Rhizospheric soils of the notorious invasive plant Wedelia trilobata with different degrees of invasion (uninvaded, low-degree, and high-degree using its coverage in the invaded ecosystems) were collected from five discrete areas in Hainan Province, P. R. China. Soil physicochemical properties and community structure of soil microorganisms were assessed. Low degrees of W. trilobata invasion significantly increased soil pH values whereas high degrees of invasion did not significantly affected soil pH values. Moreover, the degree of W. trilobata invasion exerted significant effects on soil Ca concentration but did not significantly change other indices of soil physicochemical properties. Low and high degrees of W. trilobata invasion increased the richness of the soil fungal community but did not pose obvious effects on the soil bacterial community. W. trilobata invasion also exerted obvious effects on the community structure of soil microorganisms that take part in soil nitrogen cycling. These changes in soil physicochemical properties and community structure of soil microbial communities mediated by different degrees of W. trilobata invasion may present significant functions in further facilitating the invasion process. PMID:24392015

  18. Chronic Invasive Fungal Granuloma–A Diagnostic Dilemma in an Immunocompetent Host

    PubMed Central

    S. Chavan, Shrinivas; Bhople, K.S.; Deshmukh, Sunil D; V. Jain, Prateek; Sonavani, Mangala

    2016-01-01

    Introduction: Invasive fungal sinusitis, though considered to be rare entity, is nowadays frequently encountered, not only in immunocompromised patients but also in immunocompetent patients. The changing prevalence towards immunocompetent hosts is due to the indiscriminate usage of broad spectrum antibiotics, steroids, and immunosuppressive drugs. Diagnosing invasive fungal sinusitis should not pose any difficulty to both the clinician [a whitish colour secretion in elderly Diabetics, and CT Scan PNS showing concretion in the sinus along with destruction of the surrounding bone] and to the pathologist; however, when the invasive fungal sinus infection presents in a form of a granuloma then its diagnosis imposes a challenge to medical professionals. Case Report We are presenting a case study,which consists of 3 cases of chronic invasive fungal sinus infection.Two patients were treated for tuberculoma and had completed a course of Anti Koch’s Treatment and one patient was given a trial of broad spectrum antibiotics and steroids.Eventually all cases were diagnosed as a chronic invasive form of fungal granuloma (CIFG). Conclusion: CIFG of the paranasal sinuses is seen in immunocompetent hosts, especially those that are in the 2nd and 3rd decades of their lives. Gradually progressive proptosis is the primary presenting symptom. MRI scanning is a better imaging modality compared to CT scanning. Routine H&E staining may prove inadequate and special stains such as the GMS stain should be employed in the slightest doubt of a fungal aetiology. A team approach towards patients is paramount for early diagnosis and timely medical and surgical intervention. PMID:26878009

  19. Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years*

    PubMed Central

    Shi, Ji-min; Pei, Xu-ying; Luo, Yi; Tan, Ya-min; Tie, Ru-xiu; He, Jing-song; Zheng, Wei-yan; Zhang, Jie; Cai, Zhen; Lin, Mao-fang; Huang, He

    2015-01-01

    Invasive fungal infection (IFI) is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively reviewed the records of 408 patients undergoing allo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 (22.5%) episodes suffered proven or probable IFI (4 patients were proven, 88 patients were probable). Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen (HLA) mismatch, long-time neutropenia, and acute graft-versus-host-disease (GVHD) were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus (CMV) disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival (OS) rate for IFI was significantly lower than that of patients without IFI (41.9% vs. 63.6%, P<0.01). PMID:26365122

  20. Survival following lung resection in immunocompromised patients with pulmonary invasive fungal infection

    PubMed Central

    Wu, Geena X.; Khojabekyan, Marine; Wang, Jami; Tegtmeier, Bernard R.; O'Donnell, Margaret R.; Kim, Jae Y.; Grannis, Frederic W.; Raz, Dan J.

    2016-01-01

    OBJECTIVES Pulmonary invasive fungal infections (IFIs) are associated with high mortality in patients being treated for haematological malignancy. There is limited understanding of the role for surgical lung resection and outcomes in this patient population. METHODS This is a retrospective cohort of 50 immunocompromised patients who underwent lung resection for IFI. Patient charts were reviewed for details on primary malignancy and treatment course, presentation and work-up of IFI, reasons for surgery, type of resection and outcomes including postoperative complications, mortality, disease relapse and survival. Analysis was also performed on two subgroups based on year of surgery from 1990–2000 and 2001–2014. RESULTS The median age was 39 years (range: 5–64 years). Forty-seven patients (94%) had haematological malignancies and 38 (76%) underwent haematopoietic stem cell transplantation (HSCT). Surgical indications included haemoptysis, antifungal therapy failure and need for eradication before HSCT. The most common pathogen was Aspergillus in 34 patients (74%). Wedge resections were performed in 32 patients (64%), lobectomy in 9 (18%), segmentectomy in 2 (4%) and some combination of the 3 in 7 (14%) for locally extensive, multifocal disease. There were 9 (18%) minor and 14 (28%) major postoperative complications. Postoperative mortality at 30 days was 12% (n = 6). Acute respiratory distress syndrome was the most common cause of postoperative death. Overall 5-year survival was 19%. Patients who had surgery in the early period had a median survival of 24 months compared with 5 months for those who had surgery before 2001 (P = 0.046). At the time of death, 15 patients (30%) had probable or proven recurrent IFI. Causes of death were predominantly related to refractory malignancy, fungal lung disease or complications of graft versus host disease (GVHD). Patients who had positive preoperative bronchoscopy cultures had a trend towards worse survival compared with

  1. Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4)

    PubMed Central

    Boğa, Can; Bolaman, Zahit; Çağırgan, Seçkin; Karadoğan, İhsan; Özcan, Mehmet Ali; Özkalemkaş, Fahir; Saba, Rabin; Sönmez, Mehmet; Şenol, Esin; Akan, Hamdi; Akova, Murat

    2015-01-01

    This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease. PMID:26316478

  2. [Regional laboratory network for surveillance of invasive fungal infections and antifungal susceptibility in Latin America].

    PubMed

    Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan L; Córdoba, Susana; Melhem, Marcia C; Szeszs, María W; Castañeda, Elizabeth; Martínez, Gerardo; Gabastou, Jean-Marc

    2008-02-01

    This article describes the general objectives of the Regional Laboratory Network for Surveillance of Invasive Fungal Infections and Antifungal Susceptibility in Latin America. Formation of the Network was coordinated by the Essential Medicines, Vaccines, and Health Technologies Unit of the Pan American Health Organization, with the technical and financial support of the National Center for Microbiology of the Carlos III Health Institute (Spain), and the technical support of the Microbiology Department of the Dr. C. Malbrán National Institute on Infectious Diseases (Argentina) and the Microbiology Unit of the Parasitology Service of the Adolfo Lutz Institute (Brazil). The Network's principle objectives are epidemiological surveillance of invasive fungal infections through detection of antifungal resistance and identification of emergent, invasive fungal infections; establishment of norms and common protocols for early diagnosis of mycoses; and strengthening coordination, communications, and transference mechanisms among countries. The Network must be gradually implemented and must include staff training, a systematic process for sharing technology, evaluation of diagnostic techniques, identification of fungal species, and standardized tests for antifungal susceptibility.

  3. Non-Invasive Methods to Diagnose Fungal Infections in Pediatric Patients with Hematologic Disorders

    PubMed Central

    Badiee, Parisa; Hashemizadeh, Zahra; Ramzi, Mani; Karimi, Mohammad; Mohammadi, Rasoul

    2016-01-01

    Background Invasive fungal infection (IFIs) is a major infectious complication in immunocompromised patients. Early diagnosis and initiation of antifungal therapy is important to achieve the best outcome. Objectives The current study aimed to investigate the incidence of IFIs and evaluate the diagnostic performance of non-invasive laboratory tests: serologic (β-D-glucan, galactomannan) and molecular (nested polymerase chain reaction) tests to diagnose fungal infections in hematologic pediatric patients. Patients and Methods In a cross-sectional study from October 2014 to January 2015, 321 blood samples of 62 pediatric patients with hematologic disorders and at high risk for fungal infections were analyzed. Non-invasive tests including the Platelia Aspergillus enzyme immunoassay (EIA) to detect galactomannan antigen, Glucatell for β–D–glucan and nested PCR to detect Candida and Aspergillus species-specific DNA were used in a weekly screening strategy. Results Twenty six patients (42%) were considered as proven and probable IFIs, including 3 (5%) proven and 23 (37%) probable cases. Eighteen patients (29%) were considered as possible cases. The sensitivity, specificity, positive and negative predictive values for galactomannan test in 26 patients with proven and probable fungal infections were 94.4%, 100%, 100% and 94.7%; for β-D-glucan test 92.3%, 77.7%, 85%, 87.5% and for nested-PCR were 84.6%, 88.8%, 91.7% and 80%, respectively. Conclusions The rate of IFIs in pediatric patients with hematologic disorders is high, and sample collection from the sterile sites cannot be performed in immunocompromised patients. Detection of circulating fungal cell wall components and DNA in the blood using non-invasive methods can offer diagnostic help in patients with suspected IFIs. Their results should be interpreted in combination with clinical, radiological and microbiological findings. PMID:28138379

  4. Voriconazole: a broad-spectrum triazole for the treatment of invasive fungal infections.

    PubMed

    Cecil, Jane A; Wenzel, Richard P

    2009-06-01

    Over the last 20 years, the frequency of life-threatening, invasive fungal infections has risen dramatically, corresponding to an increase in the number of immunocompromised patients. Thus, the development of newer, better tolerated, more effective antifungal drugs has become critically important. Voriconazole was the first second-generation triazole to be approved by the US FDA and the EMEA, both in 2002. Voriconazole is currently approved for the treatment of invasive aspergillosis, candidemia, candidal esophagitis and disseminated candidiasis in adults, and serious fungal infections due to Scedosporium apiospermum and Fusarium species. In addition to providing an alternative treatment option for Candida infections and many emerging and refractory invasive fungal infections, voriconazole is currently the treatment of choice for invasive aspergillosis. Voriconazole has excellent in vitro activity against a wide spectrum of yeasts and molds, with only a few notable exceptions. Although it has the potential for some unique and interesting side effects, as well as important drug-drug interactions, the use of therapeutic drug monitoring can be used to optimize its efficacy and safety.

  5. Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series

    PubMed Central

    2014-01-01

    Background Invasive fungal infections are very severe infections associated with high mortality rates, despite the availability of new classes of antifungal agents. Based on pathophysiological mechanisms and limited pre-clinical and clinical data, adjunctive immune-stimulatory therapy with interferon-gamma (IFN-γ) may represent a promising candidate to improve outcome of invasive fungal infections by enhancing host defence mechanisms. Methods In this open-label, prospective case series, we describe eight patients with invasive Candida and/or Aspergillus infections who were treated with recombinant IFN-γ (rIFN-γ, 100 μg s.c., thrice a week) for 2 weeks in addition to standard antifungal therapy. Results Recombinant IFN-γ treatment in patients with invasive Candida and/or Aspergillus infections partially restored immune function, as characterized by an increased HLA-DR expression in those patients with a baseline expression below 50%, and an enhanced capacity of leukocytes from treated patients to produce proinflammatory cytokines involved in antifungal defence. Conclusions The present study provides evidence that adjunctive immunotherapy with IFN-γ can restore immune function in fungal sepsis patients, warranting future clinical studies to assess its potential clinical benefit. Trial registration ClinicalTrials.gov - NCT01270490 PMID:24669841

  6. An invasive plant-fungal mutualism reduces arthropod diversity.

    PubMed

    Rudgers, Jennifer A; Clay, Keith

    2008-08-01

    Ecological theory holds that competition and predation are the most important biotic forces affecting the composition of communities. Here, we expand this framework by demonstrating that mutualism can fundamentally alter community and food web structure. In large, replicated field plots, we manipulated the mutualism between a dominant plant (Lolium arundinaceum) and symbiotic fungal endophyte (Neotyphodium coenophialum). The presence of the mutualism reduced arthropod abundance up to 70%, reduced arthropod diversity nearly 20%, shifted arthropod species composition relative to endophyte-free plots and suppressed the biomass and richness of other plant species in the community. Herbivorous arthropods were more strongly affected than carnivores, and for both herbivores and carnivores, effects of the mutualism appeared to propagate indirectly via organisms occurring more basally in the food web. The influence of the mutualism was as great or greater than previously documented effects of competition and predation on arthropod communities. Our work demonstrates that a keystone mutualism can significantly reduce arthropod biodiversity at a broad community scale.

  7. Invasive fungal laryngopharyngitis resulting in laryngeal destruction with complete laryngotracheal separation: Report of a case.

    PubMed

    Swiss, Tyler; Cervantes, Sergio Santino; Hinni, Michael; Lott, David G

    2017-01-01

    As the treatment of hematopoietic cancers evolves, otolaryngologists will see a higher incidence of opportunistic infections. We discuss a case of invasive fungal disease that invaded the larynx, pharynx, trachea, and pulmonary parenchyma after chemotherapy. The patient, a 46-year-old woman, presented 1 week after undergoing induction chemotherapy. Her initial symptoms were odynophagia and dysphagia. Despite encouraging findings on physical examination, her health rapidly declined and she required an urgent tracheotomy and multiple operations to address spreading necrosis. Because of her inability to heal, she was not a candidate for laryngectomy, so she was treated with conservative management. The patient was then lost to follow-up, but she returned 5 months later with laryngeal destruction and a complete laryngotracheal separation. While noninvasive fungal laryngitis is routinely encountered, its invasive counterpart is rare. The literature demonstrates that some cases completely resolve with medical therapy alone but that surgery is necessary in others. We recommend surgical debridement of all necrotic tissue.

  8. Invasive Fungal Rhinosinusitis versus Bacterial Rhinosinusitis with Orbital Complications: A Case-Control Study

    PubMed Central

    Thanaviratananich, Sanguansak

    2013-01-01

    Background. Invasive fungal rhinosinusitis with orbital complications (IFSwOC) is a life-threatening condition. The incidence of mortality has been reported to be up to 80 percent. This study was conducted to determine the risk factors, presentations, clinical, and imaging findings that could help to manage this condition promptly. Methods. We conducted a case-control study of 100 patients suffering from rhinosinusitis with orbital complications. The risk factors, clinical presentations, radiological findings, medical and surgical managements, durations of hospital stay, and mortality rate data were collected. Results. Sixty-five patients were diagnosed with IFSwOC, while the other thirty-five patients composed the control group. The most important risk factor for IFSwOC was diabetes mellitus. Visual loss and diplopia were the significant symptom predictors. The significant clinical predictors were nasal crust, oculomotor nerve, and optic nerve involvement. The CT findings of IFSwOC were sinus wall erosion and hyperdensity lesions. The mortality rate was 25.71 percent in the IFSwOC group and 3.17 percent in the control group. Conclusions. Invasive fungal rhinosinusitis with orbital complications is symptomatic of a high mortality rate. The awareness of a patient's risk factors, the presenting symptoms, signs of fungal invasion, and aggressive management will determine the success of any treatment procedures. PMID:24298218

  9. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases.

    PubMed

    Walsh, T J; Hiemenz, J W; Seibel, N L; Perfect, J R; Horwith, G; Lee, L; Silber, J L; DiNubile, M J; Reboli, A; Bow, E; Lister, J; Anaissie, E J

    1998-06-01

    The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P < .02). Among 162 patients with serum creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy.

  10. A novel insight into the immunologic basis of chronic granulomatous invasive fungal rhinosinusitis

    PubMed Central

    Rae, William; Doffinger, Rainer; Shelton, Fenella; Sproson, Eleanor; Ismail-Koch, Hasnaa; Lund, Valerie J.; Harries, Philip G.; Eren, Efrem

    2016-01-01

    Background: Chronic granulomatous invasive fungal rhinosinusitis (CGIFRS) is a rare disease. The underlying immune responses that drive the development of CGIFRS, as opposed to successful pathogen clearance and controlled inflammation, are not currently known. Objective: To characterize the immune responses associated with CGIFRS. Methods: In addition to a battery of basic investigations, more in-depth immunologic testing involves ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with interleukin (IL) 12, was undertaken to investigate cell-mediated immune responses associated with CGIFRS. Results: Ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with IL-12 identified reduced interferon gamma and increased IL-17A levels within the supernatant, which indicated increased in vivo T-helper (Th)17 responses and impaired Th1 responses compared with healthy controls. Conclusion: These findings suggest that the development of CGIFRS may be associated with an abnormally exaggerated host Th17 response, which caused failure to clear the fungal pathogen with refractory fungal infection of mucosal membranes, resulting in chronic tissue inflammation. PMID:27658186

  11. New developments in the diagnosis and management of invasive fungal infections.

    PubMed

    De Marie, S

    2000-01-01

    Invasive fungal infections in cancer patients are on the increase. Candidemia is now the fourth leading cause of bloodstream infections in many intensive care units (ICUs). Although a number of risk factors have been identified, antifungal therapy should not be started in non-neutropenic patients until a diagnosis of invasive candidiasis or candidemia is made or presumed in order to avoid the development of resistance. Even a single positive blood culture should be treated, and requires removal of intravascular lines. Fluconazole is the first line agent for treatment candidemia other than that caused by Candida glabrata or C. krusei. High-resolution CT scan pictures showing a halo sign or crescent air sign are helpful for establishing the diagnosis of invasive aspergillosis. Sandwich ELISA can be used to detect circulating galactomannan in serial serum samples. Polymerase chain reaction (PCR) of blood samples may also be used. There are only a few randomized studies of newly developed antifungal drugs compared to conventional amphotericin B (AmB). So far, both AmB colloidal dispersion and AmB lipid complex have failed to show more favorable efficacy or lesser toxicity rates, except for nephrotoxicity. Liposomal AmB, used during febrile neutropenia, did have a significantly lower toxicity rate. In neutropenic patients with invasive fungal infections liposomal AmB proved to be better than conventional AmB in terms of clinical efficacy, mortality and nephrotoxicity rates. The use of tests to achieve an earlier diagnosis combined with more potent treatment formulations such as liposomal AmB may be significant steps towards successful management of invasive fungal infections.

  12. Chlorine gas exposure increases susceptibility to invasive lung fungal infection

    PubMed Central

    Gessner, Melissa A.; Doran, Stephen F.; Yu, Zhihong; Dunaway, Chad W.; Matalon, Sadis

    2013-01-01

    Chlorine (Cl2) is a highly irritating and reactive gas with potential occupational and environmental hazards. Acute exposure to Cl2 induces severe epithelial damage, airway hyperreactivity, impaired alveolar fluid clearance, and pulmonary edema in the presence of heightened inflammation and significant neutrophil accumulation in the lungs. Herein, we investigated whether Cl2 exposure affected the lung antimicrobial immune response leading to increased susceptibility to opportunistic infections. Mice exposed to Cl2 and challenged intratracheally 24 h thereafter with the opportunistic mold Aspergillus fumigatus demonstrated an >500-fold increase in A. fumigatus lung burden 72 h postchallenge compared with A. fumigatus mice exposed to room air. Cl2-exposed A. fumigatus challenged mice also demonstrated significantly higher lung resistance following methacholine challenge and increased levels of plasma proteins (albumin and IgG) in the bronchoalveolar lavage fluid. Despite enhanced recruitment of inflammatory cells to the lungs of Cl2-exposed A. fumigatus challenged mice, these cells (>60% of which were neutrophils) demonstrated a profound impairment in generating superoxide. Significantly higher A. fumigatus burden in the lungs of Cl2 exposed mice correlated with enhanced production of IL-6, TNF-α, CXCL1, CCL2, and CCL3. Surprisingly, however, Cl2-exposed A. fumigatus challenged mice had a specific impairment in the production of IL-17A and IL-22 in the lungs compared with mice exposed to room air and challenged with A. fumigatus. In summary, our results indicate that Cl2 exposure markedly impairs the antimicrobial activity and inflammatory reactivity of myeloid cells in the lung leading to increased susceptibility to opportunistic pathogens. PMID:23564508

  13. Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections.

    PubMed

    McKeage, Kate

    2015-03-01

    Posaconazole (Noxafil(®)) is a triazole antifungal agent with an extended spectrum of antifungal activity. It is approved for the prophylaxis of invasive fungal infections in patients with neutropenia or in haematopoietic stem cell transplant recipients undergoing high-dose immunosuppressive therapy for graft-versus-host disease, and for the treatment of fungal infections. The efficacy and good tolerability of posaconazole oral suspension administered three or four times daily is well established. However, in order to overcome pharmacokinetic limitations associated with the suspension, a new gastro-resistant tablet and intravenous (IV) solution were developed. This article reviews the pharmacokinetic properties of the new posaconazole formulations and briefly summarizes efficacy data relating to the suspension. The pharmacokinetic advantages of the posaconazole gastro-resistant tablet compared with the suspension formulation include less interpatient variability, better systemic availability enabling once-daily administration, and absorption that is unaffected by changes in gastric pH or motility; in addition the tablets may be taken with or without food. The posaconazole tablet achieves higher and more consistent mean plasma concentrations than the suspension and, therefore, it is the preferred option to optimize efficacy in the prophylaxis or treatment of invasive fungal disease. The posaconazole IV solution provides an option for these same indications in patients who are unable to receive oral formulations.

  14. Invasive Fungal Infections Acquired from Contaminated Food or Nutritional Supplements: A Review of the Literature.

    PubMed

    Benedict, Kaitlin; Chiller, Tom M; Mody, Rajal K

    2016-07-01

    Fungi are an integral part of the natural environment and, therefore, play many roles in relation to food: some fungi are used in food production, some are food sources themselves, and some are agents of food spoilage. Some fungi that contaminate food can also be harmful to human health. The harmful but noninfectious health consequences of mycotoxins have been well-characterized, but the extent to which fungi in food pose a risk for invasive infections is unknown. We conducted a literature review to identify cases of invasive fungal infections (IFIs) believed to have resulted from ingestion or inhalation of food, beverages, or dietary supplements (excluding Saccharomyces infections). We identified 11 publications describing cases or small outbreaks of IFIs related to foods or beverages and three describing IFIs related to dietary supplements. These food-associated IFIs were predominantly mold infections, and the few yeast infections were associated with dairy products. Suspected foodborne IFIs appear to be rare, but are increasingly described in the electronically searchable literature. They are associated with a variety of foods, are due to a variety of fungal pathogens, and primarily occur in persons with immunosuppressive conditions or other predisposing factors. Various guidelines for high-risk patients recommend avoidance of certain food products that may contain high levels of fungi, but further work is needed to evaluate the effectiveness of these restrictive diets in preventing fungal infections. The relationships between food spoilage, food insecurity, and IFI risk are another area that may warrant further exploration.

  15. New and investigational triazole agents for the treatment of invasive fungal infections.

    PubMed

    De Sarro, A; La Camera, E; Fera, M T

    2008-12-01

    The incidence of invasive fungal infections (IFIs) caused by both common and uncommon opportunistic fungi is increasing along with emerging fungal resistance. Since traditional agents (amphotericin B, fluconazole, itraconazole) are limited by an inadequate spectrum of activity, drug resistance or toxicity, there is a great interest in the development of new antifungal agents for treatment of IFIs in high-risk populations. In recent years a number of systemic antifungal drugs have become available and options for treatment of IFIs have expanded. A new generation of triazole agents (voriconazole, posaconazole, isavuconazole, ravuconazole and albaconazole), with a broad spectrum of activity and sufficient improvements in potency to overcome resistance have emerged and represent an alternative to conventional antifungals for the prevention and treatment of IFIs. This article focuses on the microbiology, pharmacology, clinical efficacy and safety of the new antifungal triazole generation.

  16. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations.

    PubMed

    Pagano, Livio; Busca, Alessandro; Candoni, Anna; Cattaneo, Chiara; Cesaro, Simone; Fanci, Rosa; Nadali, Gianpaolo; Potenza, Leonardo; Russo, Domenico; Tumbarello, Mario; Nosari, Annamaria; Aversa, Franco

    2017-03-01

    Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations. The extensive use of antifungal prophylaxis has reduced the infections from yeasts (e.g., candidemia) even though they are still associated with high mortality rates. This paper analyzes concurrent multiple predisposing factors that could favor the onset of fungal infections. Although neutropenia is common to almost all hematologic patients, other factors play a key role in specific patients, in particular in patients with AML or allogeneic HSCT recipients. Defining those patients at higher risk of IFIs may help to design the most appropriate diagnostic work-up and antifungal strategy.

  17. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases.

    PubMed

    Ruhnke, Markus; Schwartz, Stefan

    2016-12-01

    Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay (Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the 'traditional' empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B

  18. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases

    PubMed Central

    Ruhnke, Markus; Schwartz, Stefan

    2016-01-01

    Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay (Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the ‘traditional’ empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B

  19. Risk factors for early invasive fungal disease in critically ill patients

    PubMed Central

    Singh, Gurmeet; Pitoyo, Ceva Wicaksono; Aditianingsih, Dita; Rumende, Cleopas Martin

    2016-01-01

    Background: The incidence of invasive fungal disease (IFD) is increasing worldwide in the past two to three decades. Critically ill patients in Intensive Care Units are more vulnerable to fungal infection. Early detection and treatment are important to decrease morbidity and mortality in critically ill patients. Objective: Our study aimed to assess factors associated with early IFD in critically ill patients. Materials and Methods: This prospective cohort study was conducted in critically ill patients, from March to September 2015. Total number of patients (74) in this study was drawn based on one of the risk factors (human immunodeficiency virus). Specimens were collected on day 5–7 of hospitalization. Multivariate analysis with logistic regression was performed for factors, with P < 0.25 in bivariate analysis. Results: Two hundred and six patients were enrolled in this study. Seventy-four patients were with IFD, majority were males (52.7%), mean age was 58 years (range 18–79), mean Leon's score was 3 (score range 2–5), majority group was nonsurgical/nontrauma (72.9%), and mean fungal isolation was positive on day 5. Candida sp. (92.2%) is the most frquently isolated fungal infection. Urine culture yielded the highest number of fungal isolates (70.1%). Mortality rate in this study was 50%. In multivariate analysis, diabetes mellitus (DM) (P = 0.018, odds ratio 2.078, 95% confidence interval 1.135–3.803) was found as an independent factor associated with early IFD critically ill patients. Conclusion: DM is a significant factor for the incidence of early IFD in critically ill patients. PMID:27994377

  20. New Panfungal Real-Time PCR Assay for Diagnosis of Invasive Fungal Infections.

    PubMed

    Valero, Clara; de la Cruz-Villar, Laura; Zaragoza, Óscar; Buitrago, María José

    2016-12-01

    The diagnosis of invasive fungal infections (IFIs) is usually based on the isolation of the fungus in culture and histopathological techniques. However, these methods have many limitations often delaying the definitive diagnosis. In recent years, molecular diagnostics methods have emerged as a suitable alternative for IFI diagnosis. When there is not a clear suspicion of the fungus involved in the IFI, panfungal real-time PCR assays have been used, allowing amplification of any fungal DNA. However, this approach requires subsequent amplicon sequencing to identify the fungal species involved, increasing response time. In this work, a new panfungal real-time PCR assay using the combination of an intercalating dye and sequence-specific probes was developed. After DNA amplification, a melting curve analysis was also performed. The technique was standardized by using 11 different fungal species and validated in 60 clinical samples from patients with proven and probable IFI. A melting curve database was constructed by collecting those melting curves obtained from fungal species included in the standardization assay. Results showed high reproducibility (coefficient of variation [CV] < 5%; r > 0.95) and specificity (100%). The overall sensitivity of the technique was 83.3%, with the group of fungi involved in the infection detected in 77.8% of the positive samples with IFIs covered by molecular beacon probes. Moreover, sequencing was avoided in 67.8% of these "probe-positive" results, enabling report of a positive result in 24 h. This technique is fast, sensitive, and specific and promises to be useful for improving early diagnosis of IFIs.

  1. Efficacy of liposomal amphotericin B for prophylaxis of acute or reactivation models of invasive pulmonary aspergillosis.

    PubMed

    Leleu, Christopher; Menotti, Jean; Meneceur, Pascale; Choukri, Firas; Sulahian, Annie; Garin, Yves J-F; Derouin, Francis

    2013-05-01

    The efficacy of antifungal prophylaxis for prevention of invasive aspergillosis (IA) may depend on whether IA results from recent inhalation of spores or reactivation of latent colonisation. Compare the efficacy of liposomal amphotericin B (LAmB) for prophylaxis in acute and reactivation models of IA. In the acute model, mice immunosuppressed from day 0 were challenged at day 3 with an aerosol of Aspergillus fumigatus. LAmB (15 mg kg(-1) ) was administered at day 0 or at challenge. In the reactivation model, naïve mice exposed to A. fumigatus remained untreated until clearance of spores from the lungs, then immunosuppressed to induce reactivation. A single LAmB dose was administered at start of immunosuppression. In the acute model, a single administration of LAmB at start of immunosuppression was not effective, but an additional administration resulted in a significant decrease in lung fungal burden (P < 0.05 vs. controls). A significant prophylactic efficacy was observed when LAmB was administered once at challenge (P < 0.01). In the reactivation model, a single LAmB administration at start of immunosuppression significantly reduced both reactivation rate and fungal burden vs. controls (P < 0.01). Our results show that the conditions under which IA develop and timing of administration of LAmB were determinant variables for prophylactic efficacy.

  2. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients.

    PubMed

    Walsh, T J; Hiemenz, J W; Anaissie, E

    1996-06-01

    Invasive fungal infections, including disseminated candidiasis and invasive pulmonary aspergillosis, are important causes of morbidity and mortality in neutropenic patients. The recent development of fluconazole, itraconazole, lipid formulations of amphotericin B, and recombinant cytokines have expanded our therapeutic armamentarium. Clinical trials have elucidated new strategies for utilizing these compounds in the prevention and treatment of opportunistic mycoses. The population of more severely immunocompromised patients, however, continues to expand and the spectrum of drug-resistant fungi, including but not limited to Candida spp, Fusarium spp, Zygomycetes, and dematiaceous moulds, continues to evolve, thus presenting new challenges to recent therapeutic advances. Development of new antifungal chemotherapeutic agents and novel approaches for augmentation of host response will be required to meet these new mycologic challenges.

  3. [Non-invasive ventilation and acute cardiogenic pulmonary oedema].

    PubMed

    Golmard, Céline

    2015-11-01

    Non-invasive ventilation is an integral part of therapies used in patients presenting acute cardiogenic pulmonary oedema. In cardiac intensive care, these patients are treated by teams trained and practised in this technique. The nurses play a central role in the support and monitoring of the patients.

  4. Invasive fungal infections among inpatients with acquired immune deficiency syndrome at a Chinese university hospital.

    PubMed

    Shen, Yin Zhong; Qi, Tang Kai; Ma, Jian Xin; Jiang, Xue Yan; Wang, Jiang Rong; Xu, Qing Nian; Huang, Qin; Liu, Xi Nian; Sun, Hong Qing; Lu, Hong Zhou

    2007-11-01

    Invasive fungal infections (IFIs) have become a major cause of morbidity and mortality among people with acquired immune deficiency syndrome (AIDS), however, little is known about the clinical features and prognosis of IFI in AIDS in China. This study aimed to characterise the clinical features and prognosis of IFI in AIDS patients in China. We retrospectively reviewed the records of all HIV-infected patients at a Chinese university hospital between December 2004 and May 2006. We identified 35 patients with IFI. IFIs included thrush, oesophageal candidiasis, fungal pneumonia, cryptococcosis, penicilliosis and fungaemia, 44.4% of IFIs occurred in the digestive tract, 71.8% of IFIs occurred in patients with CD4(+)T-lymphocyte counts <100 cells mm(-3). Candida albicans accounted for 57.4% of fungal pathogens isolated. All the patients received both antiretroviral and antifungal therapy; 27 patients were cured and eight died. IFI is one of the most common opportunistic infections in AIDS patients in China. IFIs mainly occur in patients with low CD4(+)T-lymphocyte counts. The majority of IFIs occur in the digestive tract. The most common pathogen causing IFI is C. albicans. The mortality rate remains high although antiretroviral therapy and many newer antifungals are available in China.

  5. Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer?

    PubMed

    Halliday, C L; Kidd, S E; Sorrell, T C; Chen, S C-A

    2015-04-01

    Rapid, accurate diagnostic laboratory tests are needed to improve clinical outcomes of invasive fungal disease (IFD). Traditional direct microscopy, culture and histological techniques constitute the 'gold standard' against which newer tests are judged. Molecular diagnostic methods, whether broad-range or fungal-specific, have great potential to enhance sensitivity and speed of IFD diagnosis, but have varying specificities. The use of PCR-based assays, DNA sequencing, and other molecular methods including those incorporating proteomic approaches such as matrix-assisted laser desorption ionisation-time of flight mass spectroscopy (MALDI-TOF MS) have shown promising results. These are used mainly to complement conventional methods since they require standardisation before widespread implementation can be recommended. None are incorporated into diagnostic criteria for defining IFD. Commercial assays may assist standardisation. This review provides an update of molecular-based diagnostic approaches applicable to biological specimens and fungal cultures in microbiology laboratories. We focus on the most common pathogens, Candida and Aspergillus, and the mucormycetes. The position of molecular-based approaches in the detection of azole and echinocandin antifungal resistance is also discussed.

  6. Prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole.

    PubMed

    Soysal, Ahmet

    2015-01-01

    Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug. Pharmacokinetic studies have found that the oral suspension form of posaconazole has problemeatic bioavailability: its absorption is affected by concomitant medication and food. This article discusses the pharmacokinetic properties of the newly developed posaconazole delayed-release tablet formulation and reviews the efficacy, safety, and cost-effectiveness of both the oral suspension and the new tablet formulation. In conclusion, the posaconazole tablet formulation has better systemic bioavailability, thereby enabling once-daily administration and better absorption in the presence of concomitant medication and food. However, well-designed clinical studies are needed to evaluate the use of the tablet formulation in real-life settings.

  7. Posaconazole prophylaxis--impact on incidence of invasive fungal disease and antifungal treatment in haematological patients.

    PubMed

    Peterson, Lisa; Ostermann, Julia; Rieger, Heidi; Ostermann, Helmut; Rieger, Christina Theresa

    2013-11-01

    Since two large-scale, randomised studies on posaconazole prophylaxis have demonstrated a clear benefit for patients at high risk for contracting invasive fungal disease (IFD), posaconazole prophylaxis has been adopted as standard of care for this patient collective. Several years on from implementation at our institution, we wanted to evaluate its impact on the incidence and use of empirical antifungal therapy in a real-life setting. We analysed retrospectively incidence and severity of IFD in high-risk patients with prophylaxis, using a historical cohort as comparator. A total of 200 patients had either received the extended spectrum triazole posaconazole in prophylactic dosage of 200 mg tid or empirical antifungal therapy. Disease events were analysed by application of the revised EORTC/MSG definitions for IFD. Before posaconazole prophylaxis, we recorded 57/100 cases of IFD which was reduced to 28/100 with prophylaxis. The empirical use of antifungal drugs was reduced to 41% from 91% in the non-prophylaxis cohort. Furthermore, we observed a shift in the categorisation of IFD according to EORTC/MSG criteria. Our data suggest that posaconazole was effective in reducing the rate and probability of invasive fungal disease in high-risk patients.

  8. Inherited fungal symbionts enhance establishment of an invasive annual grass across successional habitats.

    PubMed

    Uchitel, Andrea; Omacini, Marina; Chaneton, Enrique J

    2011-02-01

    Plants infected with vertically transmitted fungal endophytes carry their microbial symbionts with them during dispersal into new areas. Yet, whether seed-borne endophytes enhance the host plant's ability to overcome colonisation barriers and to regenerate within invaded sites remains poorly understood. We examined how symbiosis with asexual endophytic fungi (Neotyphodium) affected establishment and seed loss to predators in the invasive annual grass Lolium multiflorum (Italian ryegrass) across contrasting successional plots. Italian ryegrass seeds with high and low endophyte incidence were sown into three communities: a 1-year-old fallow field, a 15-year-old grassland, and a 24-year-old forest, which conformed to an old-field chronosequence in the eastern Inland Pampa, Argentina. We found that endophyte infection consistently increased host population recruitment and reproductive output. Endophyte presence also enhanced aerial biomass production of ryegrass in a low recruitment year but not in a high recruitment year, suggesting that symbiotic effects on growth performance are density dependent. Endophyte presence reduced seed removal by rodents, although differential predation may not account for the increased success of infected grass populations. Overall, there was no statistical evidence for an endophyte-by-site interaction, indicating that the fungal endosymbiont benefitted host establishment regardless of large differences in biotic and abiotic environment among communities. Our results imply that hereditary endophytes may increase the chances for host grass species to pass various ecological filters associated with invasion resistance across a broad range of successional habitats.

  9. Epidemiology of invasive fungal infections in lung transplant recipients on long-term azole antifungal prophylaxis.

    PubMed

    Chong, Pearlie P; Kennedy, Cassie C; Hathcock, Matthew A; Kremers, Walter K; Razonable, Raymund R

    2015-04-01

    Lung transplant recipients (LTR) at our institution receive prolonged and mostly lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (IFI) is unknown. This was a single-center, retrospective cohort study. We reviewed the medical records of all adult LTR from January 2002 to December 2011. Overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed IFI. Nineteen IFI episodes were identified (eight proven, 11 probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI: 1.15-15.91; p = 0.03). A higher hazard of mortality was observed among those who developed IFI, although this was not statistically significant (hazard ratio [HR]: 1.71; 95% confidence interval [CI] [0.58-4.05]; p = 0.27). Aspergillus fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being the most common site of infection. None of our patients developed disseminated invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue to occur in LTR, and the eradication of IFI appears to be challenging even with prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF exposure.

  10. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

    PubMed Central

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. PMID:26730212

  11. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.

    PubMed

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed.

  12. Epidemiology of invasive fungal infections after liver transplantation and the risk factors of late-onset invasive aspergillosis.

    PubMed

    Nagao, Miki; Fujimoto, Yasuhiro; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Takakura, Shunji; Uemoto, Shinji; Ichiyama, Satoshi

    2016-02-01

    Invasive fungal infection (IFI) in liver transplant recipients is associated with poor outcomes. Targeted antifungal prophylaxis is recommended for high-risk populations; however, the epidemiology of IFI has changed, and the risk criteria remain unclear. In addition, the risk factors for late-onset invasive aspergillosis (IA) have not been fully characterized. We examined 279 recipients over 16 years of age to uncover their IFI epidemiology, clinical characteristics and outcomes. In addition, a case-control study was performed to identify the risk factors of late-onset IA. Of the 279 recipients, 96.1% underwent living donor liver transplantation. Antifungal prophylaxis was administered to 80.6% of the recipients. IFI occurred in 15 patients, among which 8 cases were early-onset (≤90 days after liver transplantation) and 7 cases were late-onset (>90 days after liver transplantation). Five of the late-onset cases were invasive pulmonary aspergillosis, and 2 were fungemia cases. The mortality rate of late-onset IA was 80.0%. According to a multivariate analysis, steroid use before liver transplantation, bloodstream infection within 90 days after liver transplantation and reoperation within 90 days after liver transplantation were significant risk factors for late-onset IA after liver transplantation. The prevalence of IFI was low in our population given that over 80% of liver recipients received antifungal prophylaxis. The prognosis of late-onset IA remains poor, and predictors associated with late-onset IA, such as steroid use before liver transplantation, bloodstream infection and reoperation after liver transplantation, may help clinicians to optimize prevention measures for these devastating infections.

  13. Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

    PubMed Central

    Ju, Hyunsu; Wheat, L. Joseph; Baden, Lindsey; Stafford, Susan; Wu, Zheng; Issa, Nicolas; Caliendo, Angela M.; Denning, David W.; Soman, Kizhake; Clancy, Cornelius J.; Nguyen, M. Hong; Sugrue, Michele W.; Alexander, Barbara D.; Wingard, John R.

    2015-01-01

    Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides), fungal polysaccharides (galactomannan), and cell wall components (β-D glucan) were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS) produced a greater case classification accuracy than galactomannan (GM) or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients undergoing treatment

  14. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.

    PubMed

    Neofytos, D; Fishman, J A; Horn, D; Anaissie, E; Chang, C-H; Olyaei, A; Pfaller, M; Steinbach, W J; Webster, K M; Marr, K A

    2010-06-01

    Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received >or=2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12-week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non-lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.

  15. Comparative evaluation of pan-fungal real-time PCR, galactomannan and (1-3)-β-D-glucan assay for invasive fungal infection in paediatric cancer patients.

    PubMed

    Gupta, Prashant; Ahmad, Abrar; Khare, Vineeta; Kumar, Archana; Banerjee, Gopa; Verma, Nitya; Singh, Mastan

    2017-04-01

    Limited specific data and investigations are available for the diagnosis of Invasive Fungal Infection (IFI) in paediatrics cancer patients. Three non-invasive tests; Platelia Aspergillus EIA for galactomannan (GM), β-D-glucan (BDG) assay and pan-fungal real-time PCR for fungal DNA in blood were evaluated. One hundred twenty-five paediatrics cancer patients at the high risk of IFI were enrolled. Single blood and serum samples were evaluated by all the three methods. Patients were classified into 10 proven, 52 probable and 63 no IFI cases in accordance with EORTC MSG 2008 revised guidelines. The sensitivity, specificity, PPV and NPV of all the three tests in proven, probable and no IFIs cases were analysed singly and in combination. The sensitivity, specificity, PPV and NPV of GM, BDG and pan-fungal real-time PCR were: 87%, 61%, 81%, 69.5% for GM, 88%, 59.5%, 81%, 71.4% for BDG and 89%, 69.2%, 85%, 67.5% for PCR (95% CI). Among different combinations, best combination was found to be GM and PCR with sensitivity, specificity, PPV and NPV of 98.2%, 89.3%, 97.1% and 90% respectively. Single samples must be evaluated by combination of tests.

  16. Treatment of Invasive Fungal Infections in Renally Impaired Patients with Amphotericin B Colloidal Dispersion

    PubMed Central

    Anaissie, Elias J.; Mattiuzzi, Gloria N.; Miller, Carole B.; Noskin, Gary A.; Gurwith, Marc J.; Mamelok, Richard D.; Pietrelli, Larry A.

    1998-01-01

    Amphotericin B colloidal dispersion (ABCD) is a new formulation of conventional amphotericin B designed to minimize drug distribution in the kidney and reduce nephrotoxicity. We studied the safety and efficacy of ABCD in 133 renally compromised patients with invasive fungal infections. Patients had either nephrotoxicity from amphotericin B or preexisting renal disease. Intravenous treatment with ABCD (4 mg/kg of body weight daily) was administered for up to 6 weeks. Evaluations included clinical response to treatment and adverse events, with emphasis on changes in serum creatinine levels. ABCD did not appear to have an adverse effect on renal function: mean serum creatinine level tended to decrease slightly with days on therapy, and increases were not dose related. Complete or partial response to treatment was reported for 50% of the 133 intent-to-treat patients and 67% of the 58 evaluable patients. PMID:9517940

  17. Isavuconazole: a new and promising antifungal triazole for the treatment of invasive fungal infections.

    PubMed

    Guinea, Jesús; Bouza, Emilio

    2008-12-01

    Invasive fungal infections (IFIs) are an important cause of morbidity and mortality. Isavuconazole (BAL4815) is a promising novel broad-spectrum triazole in late-stage clinical development that has proven to be active in vitro against Aspergillus, Candida and Cryptococcus neoformans, the most common agents of IFIs. Furthermore, isavuconazole has a pharmacokinetic profile that allows oral and intravenous administration with no severe toxicity. In vivo data from animal models are also encouraging. However, very little information on clinical efficacy is available. Four clinical trials are currently in progress to demonstrate the safety and efficacy of isavuconazole for the treatment and prevention of IFIs. In the absence of clinical and cost data, the real possibilities of this agent as a competitor for the treatment and prevention of IFIs in the clinical setting are still unknown.

  18. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections.

    PubMed

    Denning, David W; Kibbler, Christopher C; Barnes, Rosemary A

    2003-04-01

    Outcomes for invasive fungal infections have greatly improved in the past decade, and several new antifungal drugs have been or will be licensed in the next few years. Early accurate diagnosis and appropriate treatment have major impact on survival. In a 1995 survey of laboratory practice in the UK for mycology, major disparities were seen, with many laboratories not undertaking even simple diagnostic procedures. Delays in processing and inadequate procedures for handling samples, incomplete or delayed reporting of results, or a combination of these, compromise the care of patients. In randomised trials of antifungal chemotherapy, optimum treatments and good alternatives for others have been defined for some infections. High-quality care requires a multidisciplinary approach to diagnosis and management. In this review, we propose microbiology, histopathology, radiology, and clinical auditing standards, with the evidence base for each reviewed. The standards are absolutes, and, therefore, provide a straightforward basis for improving services to patients if they are all implemented.

  19. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

    PubMed Central

    De Pauw, Ben; Walsh, Thomas J.; Donnelly, J. Peter; Stevens, David A.; Edwards, John E.; Calandra, Thierry; Pappas, Peter G.; Maertens, Johan; Lortholary, Olivier; Kauffman, Carol A.; Denning, David W.; Patterson, Thomas F.; Maschmeyer, Georg; Bille, Jacques; Dismukes, William E.; Herbrecht, Raoul; Hope, William W.; Kibbler, Christopher C.; Kullberg, Bart Jan; Marr, Kieren A.; Muñoz, Patricia; Odds, Frank C.; Perfect, John R.; Restrepo, Angela; Ruhnke, Markus; Segal, Brahm H.; Sobel, Jack D.; Sorrell, Tania C.; Viscoli, Claudio; Wingard, John R.; Zaoutis, Theoklis; Bennett, John E.

    2009-01-01

    Background Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results The revised definitions retain the original classifications of “proven,” “probable,” and “possible” invasive fungal disease, but the definition of “probable” has been expanded, whereas the scope of the category “possible” has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients. PMID:18462102

  20. Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

    PubMed Central

    Ge, H.F.; Liu, X.Q.; Zhu, Y.Q.; Chen, H.Q.; Chen, G.Z.

    2016-01-01

    Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI. PMID:27683823

  1. Diagnostic strategies for invasive fungal infections in patients with hematologic malignancies and hematopoietic stem cell transplant recipients.

    PubMed

    Norkin, Maxim; Wingard, John R

    2013-08-01

    Invasive fungal infections (IFIs) frequently occur and are associated with high morbidity and mortality in patients with hematologic malignancies (HMs) and hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis of IFI in these patients facilitates prompt institution of therapy and leads to improved clinical outcomes. This article reviews widely used methodologies for diagnosing IFIs in patients with HM and HSCT recipients. Advantages and limitations of radiologic studies; microbiologic and histopathologic techniques; fungal biomarker assays, including those for galactomannan antigen and β-(1-3)-D-glucan; and molecular assays that are available to establish an early diagnosis of clinically relevant invasive fungal infections are discussed. Recommendations are provided regarding effective use of these methodologies in clinical practice.

  2. [Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) guidelines for the diagnosis of invasive fungal infections. 2010 update].

    PubMed

    Ayats, Josefina; Martín-Mazuelos, Estrella; Pemán, Javier; Quindós, Guillermo; Sánchez, Fernando; García-Rodríguez, Julio; Guarro, Josep; Guinea, Jesús; Linares, María J; Pontón, José; Rodríguez-Tudela, Juan L; Cuenca-Estrella, Manuel

    2011-01-01

    These guidelines are an update of recommendations for the diagnosis of invasive fungal infections by the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) published in 2004 (Enferm Infecc Microbiol Clin. 2004, 22:32-9). In this updated version of the guidelines, a comprehensive review of the most recent diagnostic innovations and levels of evidence to recommend those diagnostic procedures are included. We first analyse conventional diagnostic methods, microscopic examination and culture, underlining their limitations which have led to the development of alternative methods, such as fungal antigen and DNA quantification. Those alternative methods of diagnosis are analysed by fungal infection. We also briefly review the methods for molecular identification of fungal species and recommendations for carrying out susceptibility tests for antifungal drugs, including reference procedures, commercial techniques and their indications.

  3. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology.

    PubMed

    Cornely, Oliver A; Böhme, Angelika; Buchheidt, Dieter; Einsele, Hermann; Heinz, Werner J; Karthaus, Meinolf; Krause, Stefan W; Krüger, William; Maschmeyer, Georg; Penack, Olaf; Ritter, Jörg; Ruhnke, Markus; Sandherr, Michael; Sieniawski, Michal; Vehreschild, Jörg-Janne; Wolf, Hans-Heinrich; Ullmann, Andrew J

    2009-01-01

    There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).

  4. Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

    PubMed

    Jarque, I; Tormo, M; Bello, J L; Rovira, M; Batlle, M; Julià, A; Tabares, S; Rivas, C; Fernández-Sevilla, A; García-Boyero, R; Debén, G; González-Campos, J; Capote, F J; Sanz, M A

    2013-02-01

    Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

  5. Risk Factors for the Development of Intra-Abdominal Fungal Infections in Acute Pancreatitis

    PubMed Central

    Schwender, Brian J.; Gordon, Stuart R.; Gardner, Timothy B.

    2015-01-01

    Objectives Intra-abdominal fungal infections (AFI) complicating acute pancreatitis arise in the context of pancreatic necrosis. Our goal was to determine which risk factors contribute to AFI in patients with acute pancreatitis. Methods Records were reviewed from 479 non-transfer patients admitted to our medical center with acute pancreatitis from 1985–2009. Using multivariable regression models, risk factors for AFI were identified. Results Out of 479 patients admitted with acute pancreatitis, 17 patients were subsequently found to have an AFI and 3 of these patients expired. The mean length of stay for patients with an AFI was 24 days and 76% were admitted to the intensive care unit. Patients with AFI were more likely to have received prophylactic antibiotics on admission (OR 1.7, 95% C.I. 1.2–2.3), TPN within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7) or to have necrosis on CT scan within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7). Multivariable regression models identified admission antibiotic use (OR 1.6, 95% C.I. 1.4–1.8) as the strongest predictor of AFI. Conclusion Admission antibiotics are the biggest risk factor for the development of intra-abdominal fungal infections in acute pancreatitis. Prophylactic antibiotics to prevent infected necrosis should therefore be discouraged. PMID:25872170

  6. Overview of fungal rhinosinusitis.

    PubMed

    Chakrabarti, Arunaloke; Das, Ashim; Panda, Naresh K

    2004-10-01

    The incidence of fungal rhinosinusitis has increased to such extent in recent years that fungal infection should be considered in all patients with chronic rhino sinusitis. In India though the disease was reported earlier only from northern regions of this country, nowadays the disease is increasingly diagnosed from other parts as well. The disease has been categorized with possible five types: acute necrothing (fulminant), chronic invasive, chronic granulomatous invasive, fungal hall (sinus mycetoma), allergic. The first three types are tissue-invasive and the last two are non-invasive fungal rhinosinusitis. However, the categorization is still controversial and open to discussion. Chronic fungal rhinosinusitis can occur in otherwise healthy host and Aspergillus flavus is the common etiological agent in Indian scenario. The pathophys iologic mechanism of the disease remains unclear. It may represent an allergic IgE response, a cell-mediated reaction, or a combination of two. Early diagnosis may prevent multiple surgical procedures and lead to effective treatment. Histopathology and radio-imaging techniques help to distinguish different types and delineate extension of disease process. Culture helps to identify the responsible etiological agent. The presence or absence oj precipitating antibody correlates well with disease progression or recovery. The most immediate need regarding management is to establish the respective roles of surgery and antifungal therapy. Non-invasive disease requires surgical debridement and sinus ventilation only, though, additional oral or local corticosterold therapy may be beneficial in allergie type. For invasive disease, the adjuvant medical therapy is recommended to prevent recurrence and further extension. Itraconazole has been found as an effective drug in such situation. Patients with acute neerotizing type require radical surgery and amphotericin B therapy.

  7. Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections.

    PubMed

    Falci, Diego R; Pasqualotto, Alessandro C

    2013-10-22

    The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position isavuconazole in the current antifungal armamentarium.

  8. Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections

    PubMed Central

    Falci, Diego R; Pasqualotto, Alessandro C

    2013-01-01

    The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position isavuconazole in the current antifungal armamentarium. PMID:24187505

  9. Application of a Non-amplification based Technology to Detect Invasive Fungal Pathogens

    PubMed Central

    Hsu, Joe L.; Binkley, Jon; Clemons, Karl V.; Stevens, David A.; Nicolls, Mark R.; Holodniy, Mark

    2014-01-01

    Current diagnostic techniques for fungal diseases could be improved with respect to sensitivity, specificity and timeliness. To address this clinical need, we adapted a non-amplification based nucleic acid detection technology to identify fungal pathogens. We demonstrate a high-specificity, detection sensitivity, reproducibility and multiplex capacity for detecting fungal strains. PMID:24359934

  10. Utilization of posaconazole oral suspension or delayed-released tablet salvage treatment for invasive fungal infection.

    PubMed

    Kim, Jong Hun; Benefield, Russell J; Ditolla, Kali

    2016-11-01

    Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed-released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 μg mL(-1) ) compared to posaconazole SUS (median 1.0 μg mL(-1) ). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST.

  11. CotH3 mediates fungal invasion of host cells during mucormycosis.

    PubMed

    Gebremariam, Teclegiorgis; Liu, Mingfu; Luo, Guanpingsheng; Bruno, Vincent; Phan, Quynh T; Waring, Alan J; Edwards, John E; Filler, Scott G; Yeaman, Michael R; Ibrahim, Ashraf S

    2014-01-01

    Angioinvasion is a hallmark of mucormycosis. Previously, we identified endothelial cell glucose-regulated protein 78 (GRP78) as a receptor for Mucorales that mediates host cell invasion. Here we determined that spore coat protein homologs (CotH) of Mucorales act as fungal ligands for GRP78. CotH proteins were widely present in Mucorales and absent from noninvasive pathogens. Heterologous expression of CotH3 and CotH2 in Saccharomyces cerevisiae conferred the ability to invade host cells via binding to GRP78. Homology modeling and computational docking studies indicated structurally compatible interactions between GRP78 and both CotH3 and CotH2. A mutant of Rhizopus oryzae, the most common cause of mucormycosis, with reduced CotH expression was impaired for invading and damaging endothelial cells and CHO cells overexpressing GRP78. This strain also exhibited reduced virulence in a diabetic ketoacidotic (DKA) mouse model of mucormycosis. Treatment with anti-CotH Abs abolished the ability of R. oryzae to invade host cells and protected DKA mice from mucormycosis. The presence of CotH in Mucorales explained the specific susceptibility of DKA patients, who have increased GRP78 levels, to mucormycosis. Together, these data indicate that CotH3 and CotH2 function as invasins that interact with host cell GRP78 to mediate pathogenic host-cell interactions and identify CotH as a promising therapeutic target for mucormycosis.

  12. Multiple introductions of divergent genetic lineages in an invasive fungal pathogen, Cryphonectria parasitica, in France.

    PubMed

    Dutech, C; Fabreguettes, O; Capdevielle, X; Robin, C

    2010-08-01

    The occurrence of multiple introductions may be a crucial factor in the successful establishment of invasive species, but few studies focus on the introduction of fungal pathogens, despite their significant effect on invaded habitats. Although Cryphonectria parasitica, the chestnut blight fungus introduced in North America and Europe from Asia during the 20th century, caused dramatic changes in its new range, the history of its introduction is not well retraced in Europe. Using 10 microsatellite loci, we investigated the genetic diversity of 583 isolates in France, where several introductions have been hypothesized. Our analyses showed that the seven most frequent multilocus genotypes belonged to three genetic lineages, which had a different and geographically limited distribution. These results suggest that different introduction events occurred in France. Genetic recombination was low among these lineages, despite the presence of the two mating types in each chestnut stand analysed. The spatial distribution of lineages suggests that the history of introductions in France associated with the slow expansion of the disease has contributed to the low observed rate of recombination among the divergent lineages. However, we discuss the possibility that environmental conditions or viral interactions could locally reduce recombination among genotypes.

  13. Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections.

    PubMed

    Folk, Alexandra; Cotoraci, Coralia; Balta, Cornel; Suciu, Maria; Herman, Hildegard; Boldura, Oana Maria; Dinescu, Sorina; Paiusan, Lucian; Ardelean, Aurel; Hermenean, Anca

    2016-01-01

    Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-α and IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.

  14. Application of Mass Spectrometry Technology to Early Diagnosis of Invasive Fungal Infections

    PubMed Central

    Mery, Alexandre; Sendid, Boualem; François, Nadine; Cornu, Marjorie; Poissy, Julien; Guerardel, Yann

    2016-01-01

    We recently developed a mass spectrometry (MS) procedure based on the detection of a serum disaccharide (MS-DS) in patients with invasive candidiasis (IC). Here, we compare the performance of MS-DS for the diagnosis of IC, invasive aspergillosis (IA), and mucormycosis (MM) with those of commercially available antigen detection tests. This retrospective study included 48 patients (23 IC patients [74 serum samples], 15 IA patients [40 serum samples], and 10 MM patients [15 serum samples]) and 49 appropriate controls (102 serum samples). MS-DS, mannan (Mnn), galactomannan (GM), and (1,3)-β-d-glucan (BDG) were detected by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS, Platelia, and Fungitell assays, respectively. For IC, the sensitivity and specificity of the MS-DS index, BDG detection, and Mnn detection were 62% and 84%, 82% and 60%, and 33% and 94% per serum sample and 83% and 69%, 96% and 31%, and 39% and 86% per patient, respectively. For IA, the corresponding values in comparison to BDG and GM detection were 83% and 81%, 62% and 95%, and 62% and 100% per serum sample and 93% and 76%, 87% and 90%, and 93% and 100% per patient, respectively. Nine of the 10 MM patients had a positive MS-DS result. MS-DS gave an early diagnosis in IC (73% positivity before blood culture), IA (positive before GM detection in six patients), and MM (positivity mainly preceded the date of diagnosis) patients. For IC, persisting MS-DS was associated with a poor prognosis. The different biomarkers were rarely detected simultaneously, suggesting different kinetics of release and clearance. For IA, MS-DS provided better complementation to GM monitoring than BDG monitoring. MS-DS detects panfungal molecules circulating during invasive fungal infections. The performance of MS-DS compared favorably with those of biological tests currently recommended for monitoring at-risk patients. Further validation of this test in multicenter studies is required. PMID:27605710

  15. Successful management of gastropulmonary fistula due to invasive fungal infection after chemotherapy and autologous stem cell transplantation: a case report

    PubMed Central

    Ričardas, Janilionis; Lina, Lukoševičiūtė; Virgilijus, Beiša; Valdemaras, Jotautas; Roberta, Petrauskaitė; Valdas, Pečeliūnas; Renata, Jucaitienė

    2016-01-01

    Background. Invasive fungal infections (IFI) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for hematologic malignancies. Acquired gastropulmonary fistula is a rare complication of IFI. Material and methods. We present a case history of a patient with malignant myeloma. She was treated with autologous stem cell transplantation and chemotherapy for three years. She had been treated with antifungal agents as well. Following a specific treatment, she developed an invasive fungal infection (IFI) of the left lung which had been complicated with left gastropulmonary fistula. The patient’s general condition was deteriorating, so it was decided to perform a surgical intervention. At the first procedure, open-window thoracostomy was created in order to facilitate treatment by daily packing of the cavity. Four weeks after the thoracostomy, a thoracomyoplasty was performed to repair a gastropleural fistula. During the laparotomy, the gastric fundus was freed from adjacent tissues and repaired. Intrathoracic transposition of the latissimus dorsi and anterior serratus muscle flaps was performed simultaneously to create a new diaphragm. The open-window thoracostomy was left open due to some small bronchial fistulas. The thoracostomy opening healed spontaneously during the following six months. Conclusion. We report what is, to the best of our knowledge, the first case of an invasive fungal infection (Geotrichum capitatum) successfully treated with intravenous amphotericin B, voriconazole, and surgery on infected soft tissues (organs) for a patient with multiple myeloma in prolonged neutropenia. The efficacy and safety of the surgery for infected soft tissues requires further evaluation. PMID:28356805

  16. Population genetic analysis of a parasitic mycovirus to infer the invasion history of its fungal host.

    PubMed

    Schoebel, Corine N; Botella, Leticia; Lygis, Vaidotas; Rigling, Daniel

    2017-02-04

    Hymenoscyphus fraxineus mitovirus 1 (HfMV1) occurs in the fungus Hymenoscyphus fraxineus, an introduced plant pathogen responsible for the devastating ash dieback epidemic in Europe. Here, we explored the prevalence and genetic structure of HfMV1 to elucidate the invasion history of both the virus and the fungal host. A total of 1298 H. fraxineus isolates (181 from Japan and 1117 from Europe) were screened for the presence of this RNA virus and 301 virus-positive isolates subjected to partial sequence analysis of the viral RNA polymerase gene. Our results indicate a high mean prevalence (78.7%) of HfMV1 across European H. fraxineus isolates, which is supported by the observed high transmission rate (average 83.8%) of the mitovirus into sexual spores of its host. In accordance with an expected founder effect in the introduced population in Europe, only 1.1% of the Japanese isolates were tested virus positive. In Europe, HfMV1 shows low nucleotide diversity but a high number of haplotypes, which seem to be subject to strong purifying selection. Phylogenetic and clustering analysis detected two genetically distinct HfMV1 groups, both present throughout Europe. This pattern supports the hypothesis that only two (mitovirus-carrying) H. fraxineus individuals were introduced into Europe as previously suggested from the bi-allelic nature of the fungus. Moreover, our data points to reciprocal mating events between the two introduced individuals, which presumably initiated the ash dieback epidemic in Europe.

  17. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

    PubMed

    Girmenia, Corrado; Raiola, Anna Maria; Piciocchi, Alfonso; Algarotti, Alessandra; Stanzani, Marta; Cudillo, Laura; Pecoraro, Clara; Guidi, Stefano; Iori, Anna Paola; Montante, Barbara; Chiusolo, Patrizia; Lanino, Edoardo; Carella, Angelo Michele; Zucchetti, Elisa; Bruno, Benedetto; Irrera, Giuseppe; Patriarca, Francesca; Baronciani, Donatella; Musso, Maurizio; Prete, Arcangelo; Risitano, Antonio Maria; Russo, Domenico; Mordini, Nicola; Pastore, Domenico; Vacca, Adriana; Onida, Francesco; Falcioni, Sadia; Pisapia, Giovanni; Milone, Giuseppe; Vallisa, Daniele; Olivieri, Attilio; Bonini, Alessandro; Castagnola, Elio; Sica, Simona; Majolino, Ignazio; Bosi, Alberto; Busca, Alessandro; Arcese, William; Bandini, Giuseppe; Bacigalupo, Andrea; Rambaldi, Alessandro; Locasciulli, Anna

    2014-06-01

    Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival. The cumulative incidence of PP-IFDs was 5.1% at 40 days, 6.7% at 100 days, and 8.8% at 12 months post-transplantation. Multivariate analysis identified the following variables as associated with PP-IFDs: transplant from an unrelated volunteer donor or cord blood, active acute leukemia at the time of transplantation, and an IFD before transplantation in the early phase; transplant from an unrelated volunteer donor or cord blood and grade II-IV acute graft-versus-host disease (GVHD) in the late phase; and grade II-IV acute GVHD and extensive chronic GVHD in the very late phase. The risk for PP-IFD was significantly higher when acute GVHD was followed by chronic GVHD and when acute GVHD occurred in patients undergoing transplantation with grafts from other than matched related donors. The presence of PP-IFD was an independent factor in long-term survival (hazard ratio, 2.90; 95% confidence interval, 2.32 to 3.62; P < .0001). Our findings indicate that tailored prevention strategies may be useful in subpopulations at differing levels of risk for PP-IFDs.

  18. Sinonasal Fungal Infections and Complications: A Pictorial Review

    PubMed Central

    Gavito-Higuera, Jose; Mullins, Carola Birgit; Ramos-Duran, Luis; Sandoval, Hugo; Akle, Nassim; Figueroa, Ramon

    2016-01-01

    Fungal infections of the nose and paranasal sinuses can be categorized into invasive and non-invasive forms. The clinical presentation and course of the disease is primarily determined by the immune status of the host and can range from harmless or subtle presentations to life threatening complications. Invasive fungal infections are categorized into acute, chronic or chronic granulomatous entities. Immunocompromised patients with poorly controlled diabetes mellitus, HIV and patients receiving chemotherapy or chronic oral corticosteroids are mostly affected. Mycetoma and Allergic Fungal Rhinosinusitis are considered non-invasive forms. Computer tomography is the gold-standard in sinonasal imaging and is complimented by Magnetic resonance imaging (MRI) as it is superior in the evaluation of intraorbital and intracranial extensions. The knowledge and identification of the characteristic imaging patterns in invasive – and non- invasive fungal rhinosinusitis is crucial and the radiologist plays an important role in refining the diagnosis to prevent a possible fatal outcome. PMID:27403401

  19. Treatment of invasive fungal infections in high risk hematological patients. The outcome with liposomal amphotericin B is not negatively affected by prior administration of mold-active azoles.

    PubMed

    De la Serna, Javier; Jarque, Isidro; López-Jiménez, Javier; Fernández-Navarro, Jose María; Gómez, Valle; Jurado, Manuel; Pascual, Adriana; Serrano, Josefina; Romero, Mónica; Vallejo, Carlos

    2013-03-01

    There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.

  20. Diagnosis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-2)

    PubMed Central

    Arıkan Akdağlı, Sevtap; Azap, Alpay; Başaran Demirkazık, Figen; Ener, Beyza; Aşcıoğlu Hayran, Sibel; Özdemir Kumbasar, Özlem; Metan, Gökhan; Odabaşı, Zekaver; Uzun, Ömrüm; Akan, Hamdi

    2014-01-01

    One of the most problematic issues in hematological malignancies is the diagnosis of invasive fungal diseases. Especially, the difficulty of mycological diagnosis and the necessity of immediate intervention in molds have led to the adoption of “surrogate markers” that do not verify but rather strongly suggest fungal infection. The markers commonly used are galactomannan (GM), beta-glucan, and imaging methods. Although there are numerous studies on these diagnostic approaches, none of these markers serve as a support for the clinician, as is the case in human immunodeficiency virus (HIV) or cytomegalovirus (CMV) infections. This paper has been prepared to explain the diagnostic tests. As molecular tests have not been standardized and are not used routinely in the clinics, they will not be mentioned here. PMID:25541650

  1. Diagnosis of invasive fungal infections in hematology and oncology--guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO).

    PubMed

    Ruhnke, M; Böhme, A; Buchheidt, D; Cornely, O; Donhuijsen, K; Einsele, H; Enzensberger, R; Hebart, H; Heussel, C P; Horger, M; Hof, H; Karthaus, M; Krüger, W; Maschmeyer, G; Penack, O; Ritter, J; Schwartz, S

    2012-04-01

    Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either 'empirical' or 'preemptive' antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.

  2. Invasive infection in an acute myeloblastic leukemia patient due to triazole-resistant Candida tropicalis.

    PubMed

    de Carvalho Parahym, Ana Maria Rabelo; da Silva, Carolina Maria; Leão, Mariele Porto Carneiro; Macario, Michele Chianca; Filho, Gustavo Antônio da Trindade Meira Henriques; de Oliveira, Neiva Tinti; Neves, Rejane Pereira

    2011-11-01

    Non-albicans Candida species are being increasingly reported as causes of nosocomial fungal infections. For example, invasive candidiasis caused by C. tropicalis has been associated with hematologic malignancies. In this study, we report a fatal case of fungemia and a possible urinary and pulmonary infection in a leukemia patient that was due to a strain of C. tropicalis resistant to 2 triazole antifungals.

  3. Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections.

    PubMed

    Moen, Marit D; Lyseng-Williamson, Katherine A; Scott, Lesley J

    2009-01-01

    Liposomal amphotericin B (AmBisome) is a lipid-associated formulation of the broad-spectrum polyene antifungal agent amphotericin B. It is active against clinically relevant yeasts and moulds, including Candida spp., Aspergillus spp. and filamentous moulds such as Zygomycetes, and is approved for the treatment of invasive fungal infections in many countries worldwide. It was developed to improve the tolerability profile of amphotericin B deoxycholate, which was for many decades considered the gold standard of antifungal treatment, despite being associated with infusion-related events and nephrotoxicity. In well controlled trials, liposomal amphotericin B had similar efficacy to amphotericin B deoxycholate and amphotericin B lipid complex as empirical therapy in adult and paediatric patients with febrile neutropenia. In addition, caspofungin was noninferior to liposomal amphotericin B as empirical therapy in adult patients with febrile neutropenia. For the treatment of confirmed invasive fungal infections, liposomal amphotericin B was more effective than amphotericin B deoxycholate treatment in patients with disseminated histoplasmosis and AIDS, and was noninferior to amphotericin B deoxycholate in patients with acute cryptococcal meningitis and AIDS. In adults, micafungin was shown to be noninferior to liposomal amphotericin B for the treatment of candidaemia and invasive candidiasis. Data from animal studies suggested that higher dosages of liposomal amphotericin B might improve efficacy; however, in the AmBiLoad trial in patients with invasive mould infection, there was no statistical difference in efficacy between the standard dosage of liposomal amphotericin B 3 mg/kg/day and a higher 10 mg/kg/day dosage, although the standard dosage was better tolerated. Despite being associated with fewer infusion-related adverse events and less nephrotoxicity than amphotericin B deoxycholate and amphotericin B lipid complex, liposomal amphotericin B use is still limited to

  4. Probiotic supplementation for preventing invasive fungal infections in preterm neonates--a systematic review and meta-analysis.

    PubMed

    Agrawal, Sachin; Rao, Shripada; Patole, Sanjay

    2015-11-01

    Invasive fungal infections (IFI) are associated with significant health burden in preterm neonates. The objective of this study was to systematically review effect of probiotic supplementation (PS) for preventing IFI in preterm neonates. We searched Cochrane Central Register of Controlled Trials, Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, and proceedings of the Pediatric Academic Society meetings in August 2014. Study selection was performed on randomised controlled trials (RCT) of PS in neonates born <37 weeks. Primary outcome of this study was IFI (Isolation of fungus in blood/body fluids) and secondary outcome was fungal gut colonisation. Information on IFI/colonisation was available in 8 of 27 RCT. Meta-analysis (fixed effects model) showed that PS reduced the risk of IFI (RR: 0.50, 95% CI: 0.34, 0.73, I(2) = 39%). Results were not significant with random effects model (RR: 0.64, 95%, CI: 0.30, 1.38, P = 0.25, I(2) = 39%). Analysis after excluding the study with a high baseline incidence (75%) of IFI showed that PS had no significant benefits (RR: 0.89; 95% CI: 0.44, 1.78). Of the five studies reporting on fungal gut colonisation, three reported benefits of probiotics; two did not. Current evidence is limited to derive firm conclusions on the effect of PS for preventing IFI/gut colonisation in preterm neonates.

  5. Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study.

    PubMed

    Lewis, Russell E; Cahyame-Zuniga, Lizebeth; Leventakos, Konstantinos; Chamilos, Georgios; Ben-Ami, Ronen; Tamboli, Pheroze; Tarrand, Jeffrey; Bodey, Gerald P; Luna, Mario; Kontoyiannis, Dimitrios P

    2013-11-01

    Autopsy studies remain an essential tool for understanding the patterns of fungal disease not detected ante mortem with current diagnostic approaches. We collected data concerning the microbiological trends, patient clinical characteristics and sites of involvement for invasive fungal infections (IFIs) identified at autopsy in a single large cancer treatment centre over a 20-year period (1989-2008). The autopsy rate and IFI prevalence both declined significantly during the study period. The prevalence of Aspergillus spp. decreased significantly from the first 15 years of the study (from 0.12 to 0.14 cases per 100 autopsies to 0.07 in 2004-2008; P = 0.04), with only Mucorales accounting for a greater proportion of IFIs over the duration of the study period (0.06 to 0.2 cases per 100 autopsies, P = 0.04). After 2003, moulds accounted for the majority of infections identified at autopsy in the spleen, kidney, heart and gastrointestinal tract. Despite a trend of decreasing prevalence from 1989 to 2004, invasive candidiasis increased in prevalence during later periods 2004-2008 (0.02-0.05 per 100 autopsies) with decreasing kidney, heart and spleen involvement. Despite a declining autopsy rate, these data suggest a decreasing prevalence overall of IFIs with changing patterns of dissemination in patients with haematological malignancies.

  6. Spatial patterns of ectomycorrhizal fungal inoculum in arbuscular mycorrhizal barrens communities: implications for controlling invasion by Pinus virginiana.

    PubMed

    Thiet, Rachel K; Boerner, R E J

    2007-09-01

    Invasion of globally threatened ecosystems dominated by arbuscular mycorrhizal plants, such as the alkaline prairies and serpentine barrens of eastern North America, by species of ectomycorrhizal (ECM) pine (Pinus) seriously threatens the persistence, conservation, and ongoing restoration of these rare plant communities. Using Maryland serpentine barrens and an Ohio alkaline prairie complex as model systems, we tested the hypothesis that the invasiveness of Virginia pine (Pinus virginiana L.) into such communities is regulated by the spatial pattern of ECM fungal inoculum in the soil. ECM colonization of pine seedlings can occur by (1) hyphae growing from the roots of mature ECM pines colonizing nearby seedlings (contagion model), (2) pine seedlings being infected after germinating in open areas where spores are concentrated in feces of animals that have consumed sporocarps (centers of infection model), and (3) colonization from spores that are wind-dispersed across the landscape (background model). To test these models of dispersal of ECM fungal inoculum into these barrens, we used autocorrelation and spatially explicit mapping techniques (semivariance analysis and kriging) to characterize the distribution and abundance of ECM inoculum in soil. Our results strongly suggest that ECM fungi most often disperse into open barrens by contagion, thereby facilitating rapid pine colonization in an advancing front from mature pine forests bordering the barrens. Spatial patterns consistent with the centers of infection model were present but less common. Thus, current management techniques that rely on cutting and fire to reverse pine invasion may be ineffective because they do not kill or disrupt hyphal mats attached to mature roots of neighboring pines. Management alternatives are discussed.

  7. Non-invasive ventilation in acute respiratory failure in children

    PubMed Central

    Abadesso, Clara; Nunes, Pedro; Silvestre, Catarina; Matias, Ester; Loureiro, Helena; Almeida, Helena

    2012-01-01

    The aim of this paper is to assess the clinical efficacy of non-invasive ventilation (NIV) in avoiding endotracheal intubation (ETI), to demonstrate clinical and gasometric improvement and to identify predictive risk factors associated with NIV failure. An observational prospective clinical study was carried out. Included Patients with acute respiratory disease (ARD) treated with NIV, from November 2006 to January 2010 in a Pediatric Intensive Care Unit (PICU). NIV was used in 151 patients with acute respiratory failure (ARF). Patients were divided in two groups: NIV success and NIV failure, if ETI was required. Mean age was 7.2±20.3 months (median: 1 min: 0,3 max.: 156). Main diagnoses were bronchiolitis in 102 (67.5%), and pneumonia in 44 (29%) patients. There was a significant improvement in respiratory rate (RR), heart rate (HR), pH, and pCO2 at 2, 6, 12 and 24 hours after NIV onset (P<0.05) in both groups. Improvement in pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) was verified at 2, 4, 6, 12 and 24 hours after NIV onset in the success group (P<0.001). In the failure group, significant SpO2/FiO2 improvement was only observed in the first 4 hours. NIV failure occurred in 34 patients (22.5%). Risk factors for NIV failure were apnea, prematurity, pneumonia, and bacterial co-infection (P<0.05). Independent risk factors for NIV failure were apneia (P<0.001; odds ratio 15.8; 95% confidence interval: 3.42–71.4) and pneumonia (P<0.001, odds ratio 31.25; 95% confidence interval: 8.33–111.11). There were no major complications related with NIV. In conclusion this study demonstrates the efficacy of NIV as a form of respiratory support for children and infants with ARF, preventing clinical deterioration and avoiding ETI in most of the patients. Risk factors for failure were related with immaturity and severe infection. PMID:22802994

  8. A native fungal symbiont facilitates the prevalence and development of an invasive pathogen-native vector symbiosis.

    PubMed

    Zhao, Lilin; Lu, Min; Niu, Hongtao; Fang, Guofei; Zhang, Shuai; Sun, Jianghua

    2013-12-01

    Invasive pathogen-insect symbioses have been extensively studied in many different ecological niches. Whether the damage of symbioses in different introduced regions might be influenced by other microorganisms has, however, received little attention. Eight years of field data showed that the varied levels of the nematode and beetle populations and infested trees of the invasive Bursaphelenchus xylophilus--Monochamus alternatus symbiosis were correlated with patterns in the isolation frequencies of ophiostomatoid fungi at six sites, while the laboratory experiments showed that the nematode produced greater numbers of offspring with a female-biased sex ratio and developed faster in the presence of one native symbiotic ophiostomatoid fungus, Sporothrix sp. 1. Diacetone alcohol (DAA) from xylem inoculated with Sporothrix sp. 1 induced B. xylophilus to produce greater numbers of offspring. Its presence also significantly increased the growth and survival rate of M. alternatus, and possibly explains the prevalence of the nematode-vector symbiosis when Sporothrix sp. 1 was dominant in the fungal communities. Studying the means by which multispecies interactions contributed to biogeographical dynamics allowed us to better understand the varied levels of damage caused by biological invasion across the invaded range.

  9. Liposomal amphotericin B (AmBisome) efficacy in confirmed invasive aspergillosis and other filamentous fungal infections in immunocompromised hosts: a pooled analysis.

    PubMed

    Cordonnier, C; Bresnik, M; Ebrahimi, R

    2007-05-01

    A pooled efficacy analysis applying current diagnostic standards for case selection was performed on previously published trials of liposomal amphotericin B for invasive filamentous fungal infections (IFFI). Favourable responses were observed in 51% of microbiologically confirmed cases of proven or probable IFFI. Despite the limitations inherent in a retrospective analysis of pooled studies, the response rates observed in this analysis were consistent with previous reports for antifungal therapy with amphotericin B deoxycholate or voriconazole in the treatment of invasive aspergillosis.

  10. Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia.

    PubMed

    Duarte, Rafael F; López-Jiménez, Javier; Cornely, Oliver A; Laverdiere, Michel; Helfgott, David; Haider, Shariq; Chandrasekar, Pranatharthi; Langston, Amelia; Perfect, John; Ma, Lei; van Iersel, Marlou L P S; Connelly, Nancy; Kartsonis, Nicholas; Waskin, Hetty

    2014-10-01

    Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).

  11. [Non-invasive mechanical ventilation in the treatment of acute heart failure].

    PubMed

    Alfonso Megido, Joaquín; González Franco, Alvaro

    2014-03-01

    When acute heart failure progresses and there is acute cardiogenic pulmonary edema, routine therapeutic measures should be accompanied by other measures that help to correct oxygenation of the patient. The final and most drastic step is mechanical ventilation. Non-invasive ventilation has been developed in the last few years as a method that attempts to improve oxygenation without the need for intubation, thus, in theory, reducing morbidity and mortality in these patients. The present article describes the controversies surrounding the results of this technique and discusses its indications. The article also discusses how to start non-invasive ventilation in patients with acute pulmonary edema from a practical point of view.

  12. CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System

    PubMed Central

    Swamydas, Muthulekha; Rodriguez, Carlos A.; Lim, Jean K.; Mendez, Laura M.; Fink, Danielle L.; Hsu, Amy P.; Zhai, Bing; Karauzum, Hatice; Mikelis, Constantinos M.; Rose, Stacey R.; Ferre, Elise M. N.; Yockey, Lynne; Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D.; Lin, Xin; Chittiboina, Prashant; Datta, Sandip K.; Belhorn, Thomas H.; Weimer, Eric T.; Hernandez, Michelle L.; Hohl, Tobias M.; Kuhns, Douglas B.; Lionakis, Michail S.

    2015-01-01

    Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. PMID:26679537

  13. Potential role of aerosolized amphotericin B formulations in the prevention and adjunctive treatment of invasive fungal infections.

    PubMed

    Drew, Richard

    2006-06-01

    The incidence of invasive fungal infections (IFIs) continues to increase, largely due to the steady rise in the number of at-risk patients and the increased use of aggressive immunosuppressant agents. Many available treatments are often limited by concerns about efficacy, safety, drug interactions, and/or cost. Owing to the poor treatment outcomes of immunosuppressed patients with IFIs, new preventative and treatment strategies are being investigated. Among these are the aerosolized formulations of amphotericin B. Published experience with the use of aerosolized amphotericin B deoxycholate (AmBd) in the prevention of IFIs has raised concerns regarding challenges in drug administration and tolerability. However, evolving data regarding administration of lipid-based formulations of amphotericin B indicate potential advantages over AmBd in the prevention and adjunctive treatment of IFIs.

  14. Early Complications and Outcomes in Combat Injury Related Invasive Fungal Wound Infections: A Case-Control Analysis

    PubMed Central

    Lewandowski, Louis R.; Weintrob, Amy C.; Tribble, David R.; Rodriguez, Carlos J.; Petfield, Joseph; Lloyd, Bradley A.; Murray, Clinton K.; Stinner, Daniel; Aggarwal, Deepak; Shaikh, Faraz; Potter, Benjamin K.

    2015-01-01

    Objective Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures prior to initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure. Design Retrospective review and case-control analysis. Setting Military hospitals. Patients/Participants United States military personnel injured during combat operations (2009–2011). The IFI cases were identified based upon the presence of recurrent, necrotic extremity wounds with mold growth in culture and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury. Intervention None. Main Outcome Measurements Amputation revision rate and loss of functional levels. Results Seventy-one IFI cases (112 fungal-infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (p<0.001). Additionally, significantly (p<0.001) higher number of operative procedures and longer duration to initial wound closure was associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% CI: 1.17, 2.01). The supplemental matching analysis found similar results. Conclusions Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates. PMID:26360542

  15. Epidemiology of invasive fungal infections in patients with acquired immunodeficiency syndrome at a reference hospital for infectious diseases in Brazil.

    PubMed

    de Oliveira, Renata Buccheri; Atobe, Jane Harumi; Souza, Simone Aparecida; de Castro Lima Santos, Daniel Wagner

    2014-08-01

    Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20-25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.

  16. High loading dose AmBisome is efficacious and well tolerated in the management of invasive fungal infection in hematology patients.

    PubMed

    McLintock, Lorna A; Cook, Gordon; Holyoake, Tessa L; Jones, Brian L; Kinsey, Sally E; Jackson, Graham H

    2007-04-01

    Despite improved supportive care, and the introduction of less toxic lipid-formulations of amphotericin B deoxycholate and other new antifungal agents the mortality from invasive fungal infection (IFI) in hematology patients remains high. New management strategies are therefore required to improve outcome.

  17. Incidence and management of proven and probable fungal infections in patients with acute leukemia: a single center experience.

    PubMed

    Fanci, R; Casini, C; Leoni, F; Ciolli, S; Bosi, A

    2004-12-01

    The incidence of fungal infections and the role of liposomal amphotericin B (Ambisome) in proven and probable infections were evaluated in acute leukemic patients, intolerant to conventional amphotericin B. During 1999-2002, 307 febrile episodes occurred in 231 patients. Fungi were responsible for 3% of bloodstream infections. Ambisome was employed in 5 fungal sepsis (1 Candida albicans, 1 C. famata, 1 C. tropicalis, 1 C. krusei, 1 Geotrichum capitatum) 2 Aspergillosis, 2 probable fungal pneumonia cases. A favorable response was achieved in 78% of patients (4 fungemia, 2 aspergillosis, 1 probable), an unfavorable response in 1 C. krusei fungemia and in 1 probable pneumonia. Our antimicrobial pattern documented a high resistance rate to azoles. We concluded that Ambisome is an effective and well tolerated agent and its introduction has changed the outcome for many patients, although in some refractory diseases other strategies must be considered.

  18. Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients.

    PubMed

    Noskin, G; Pietrelli, L; Gurwith, M; Bowden, R

    1999-04-01

    Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, AMPHOCIL), a lipid complex of amphotericin B, was developed to reduce the nephrotoxicity of amphotericin B while retaining its antifungal efficacy. In this retrospective review, the efficacy and safety of ABCD were evaluated in 220 BMT recipients (167 allogeneic; 53 autologous) with suspected or documented life-threatening fungal infections (primarily Candida or Aspergillus species). Patients were treated in five open-label clinical trials of ABCD therapy. ABCD was administered intravenously once daily, median dose of 4 mg/kg, for up to 409 days (mean 23 days, median 16 days). Successful therapeutic response to treatment (complete or partial) was reported in 52% of the 99 evaluable patients with proven infection, and in 40% of all 220 patients. In the evaluable population, the response and mortality rates were 51% and 73%, respectively, in the allogeneic BMT patients, compared to 52% and 48% in the autologous BMT patients. The response rate for evaluable patients with Candida spp was 65%, 38% for patients with Aspergillus spp, and 42 % for patients with other or multiple fungal infections. In this patient population at high risk of nephrotoxicity due to concomitant cyclosporine and/or other nephrotoxic agents, ABCD did not cause renal dysfunction. Although the majority of patients had pre-existing renal impairment (median baseline serum creatinine 1.8 mg/dl), there was no trend towards increasing serum creatinine. No unexpected toxicities were observed. In conclusion, ABCD appears to be safe and effective for the treatment of severe fungal infections in BMT patients.

  19. THE UTILITY OF BRONCHOALVEOLAR LAVAGE BETA-D-GLUCAN TESTING FOR THE DIAGNOSIS OF INVASIVE FUNGAL INFECTIONS

    PubMed Central

    Rose, Stacey R.; Vallabhajosyula, Saraschandra; Velez, Miguel G.; Fedorko, Daniel P.; VanRaden, Mark J.; Gea-Banacloche, Juan C.; Lionakis, Michail S.

    2014-01-01

    SUMMARY Objectives To investigate the utility of beta-D-glucan (BDG) testing in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive fungal infection (IFI), as compared to BAL galactomannan (GM). Methods We retrospectively reviewed medical records of 132 consecutive patients at the National Institutes of Health (NIH) in whom BAL BDG testing was performed for diagnosis of pneumonia. Using the European Organization for Research and Treatment of Cancer/Mycoses Study Group guidelines, we determined which patients had proven or probable IFI, and assessed the diagnostic performance of BAL BDG testing, relative to BAL GM. We also determined the reproducibility of the BDG assay in BAL via repeat testing of patient samples. Results Ten patients had Pneumocystis pneumonia, and 34 patients had proven/probable IFI, including 14 with invasive aspergillosis (IA). BAL BDG was 100% sensitive for Pneumocystis. Although BAL BDG had similar sensitivity to BAL GM for the diagnosis of IA and IFI, it exhibited inferior specificity. Repeat testing demonstrated poor reproducibility of the BDG assay in BAL but not in serum. Conclusions BDG testing exhibits poor specificity and reproducibility in BAL. Identification of the BAL-specific factors that may interfere with the performance of the assay could improve the clinical usefulness of BAL BDG testing. PMID:24797077

  20. Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study).

    PubMed

    Kovanda, Laura L; Desai, Amit V; Lu, Qiaoyang; Townsend, Robert W; Akhtar, Shahzad; Bonate, Peter; Hope, William W

    2016-08-01

    Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.).

  1. Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study)

    PubMed Central

    Kovanda, Laura L.; Desai, Amit V.; Lu, Qiaoyang; Townsend, Robert W.; Akhtar, Shahzad; Bonate, Peter

    2016-01-01

    Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.) PMID:27185799

  2. Non-invasive ventilation in acute cardiogenic pulmonary oedema

    PubMed Central

    Agarwal, R; Aggarwal, A; Gupta, D; Jindal, S

    2005-01-01

    Non-invasive ventilation (NIV) is the delivery of assisted mechanical ventilation to the lungs, without the use of an invasive endotracheal airway. NIV has revolutionised the management of patients with various forms of respiratory failure. It has decreased the need for invasive mechanical ventilation and its attendant complications. Cardiogenic pulmonary oedema (CPO) is a common medical emergency, and NIV has been shown to improve both physiological and clinical outcomes. From the data presented herein, it is clear that there is sufficiently high level evidence to favour the use of continuous positive airway pressure (CPAP), and that the use of CPAP in patients with CPO decreases intubation rate and improves survival (number needed to treat seven and eight respectively). However, there is insufficient evidence to recommend the use of bilevel positive airway pressure (BiPAP), probably the exception being patients with hypercapnic CPO. More trials are required to conclusively define the role of BiPAP in CPO. PMID:16210459

  3. High-Throughput Sequencing Reveals Drastic Changes in Fungal Communities in the Phyllosphere of Norway Spruce (Picea abies) Following Invasion of the Spruce Bud Scale (Physokermes piceae).

    PubMed

    Menkis, Audrius; Marčiulynas, Adas; Gedminas, Artūras; Lynikienė, Jūratė; Povilaitienė, Aistė

    2015-11-01

    The aim of this study was to assess the diversity and composition of fungal communities in damaged and undamaged shoots of Norway spruce (Picea abies) following recent invasion of the spruce bud scale (Physokermes piceae) in Lithuania. Sampling was done in July 2013 and included 50 random lateral shoots from ten random trees in each of five visually undamaged and five damaged 40-50-year-old pure stands of P. abies. DNA was isolated from 500 individual shoots, subjected to amplification of the internal transcribed spacer of fungal ribosomal DNA (ITS rDNA), barcoded and sequenced. Clustering of 149,426 high-quality sequences resulted in 1193 non-singleton contigs of which 1039 (87.1 %) were fungal. In total, there were 893 fungal taxa in damaged shoots and 608 taxa in undamaged shoots (p < 0.0001). Furthermore, 431 (41.5 %) fungal taxa were exclusively in damaged shoots, 146 (14.0 %) were exclusively in undamaged shoots, and 462 (44.5 %) were common to both types of samples. Correspondence analysis showed that study sites representing damaged and undamaged shoots were separated from each other, indicating that in these fungal communities, these were largely different and, therefore, heavily affected by P. piceae. In conclusion, the results demonstrated that invasive alien tree pests may have a profound effect on fungal mycobiota associated with the phyllosphere of P. abies, and therefore, in addition to their direct negative effect owing physical damage of the tissue, they may also indirectly determine health, sustainability and, ultimately, distribution of the forest tree species.

  4. [Guidelines for the treatment of invasive fungal disease by Aspergillus spp. and other fungi issued by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). 2011 Update].

    PubMed

    Fortún, Jesús; Carratalá, Jordi; Gavaldá, Joan; Lizasoain, Manuel; Salavert, Miguel; de la Cámara, Rafael; Borges, Marcio; Cervera, Carlos; Garnacho, José; Lassaleta, Álvaro; Lumbreras, Carlos; Sanz, Miguel Ángel; Ramos, José T; Torre-Cisneros, Julián; Aguado, José M; Cuenca-Estrella, Manuel

    2011-01-01

    The guidelines on the treatment of invasive fungal disease by Aspergillus spp. and other fungi issued by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) are presented. These recommendations are focused on four clinical categories: oncology-haematology patients, solid organ transplant recipients, patients admitted to intensive care units, and children. An extensive review is made of therapeutical advances and scientific evidence in these settings. These guidelines have been prepared according the SEIMC consensus rules by a working group composed of specialists in infectious diseases, clinical microbiology, critical care medicine, paediatrics and oncology-haematology. Specific recommendations on the prevention of fungal infections in these patients are included.

  5. Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations.

    PubMed

    Pitman, Stuart K; Drew, Richard H; Perfect, John R

    2011-09-01

    Introduction: Morbidity and mortality associated with invasive fungal infections (IFIs) remains unacceptably high. Such diseases represent a substantial burden to the healthcare system. New options are needed to address antifungal resistance in existing and emerging pathogens and improve treatment outcomes while minimizing drug-related toxicities and interactions. Awareness of new and potential future options is of great value for those healthcare professionals who care for patients with IFIs. Areas covered: A search of PubMed, infectious diseases conference abstracts and reference lists from relevant publications was conducted and relevant information abstracted. This review describes the limitations of existing systemic antifungal therapies (e.g., resistance, drug-drug interactions, drug-related toxicities) and summarizes data regarding several emerging antifungal compounds including (but not limited to) new triazoles (e.g. isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin Z. Agents in clinical trials such as (but not limited to) new triazoles (e.g., isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin are included. New formulations of existing drugs including reformulations of miconazole, posaconazole and amphotericin B are also reviewed. Finally, new or novel administration strategies for existing drugs such as combination antifungal therapy, antifungal dose escalation, adjunctive use of iron chelators and preemptive therapy are discussed. Expert opinion: All present antifungal agents have some deficiencies in antifungal spectra, toxicity, pharmacokinetics and/or drug-drug interactions, making them less than ideal for some fungal infections. Therefore, there remains an urgent need to find safe, effective, rapidly fungicidal, broad-spectrum antifungal agents with excellent pharmacodynamics to effectively eliminate the fungus from the body with short antifungal courses.

  6. Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections.

    PubMed

    Sanz-Rodriguez, C; Lopez-Duarte, M; Jurado, M; Lopez, J; Arranz, R; Cisneros, J-M; Martino, M L; Garcia-Sanchez, P J; Morales, P; Olivé, T; Rovira, M; Solano, C

    2004-07-01

    Caspofungin, an echinocandin antifungal agent, is active against invasive Aspergillus and Candida infections. In a phase I study in healthy volunteers, mild transient increases in serum aminotransferases were observed with the concomitant administration of caspofungin and cyclosporin A (CsA). As a result, it is recommended that the concomitant use of the two drugs be limited to those settings with appropriate risk-benefit balance. We retrospectively assessed safety data in 14 patients with refractory invasive mycoses who were treated concomitantly with CsA and caspofungin before the drug was licensed in Spain. In all, 13 patients were adults (median age, 31.5 years; range, 14-67 years). The average duration of concomitant therapy was 15 days (range, 2-43 days). No clinically significant elevations of serum aminotransferases were observed, and no patient had concomitant therapy discontinued or interrupted due to a drug-related adverse event. In this study of a limited number of patients, the coadministration of caspofungin and CsA was generally well tolerated.

  7. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

    PubMed

    Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

    2016-04-19

    Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe.

  8. Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high-risk liver transplantation recipients: A propensity score analysis.

    PubMed

    Fortún, Jesús; Muriel, Alfonso; Martín-Dávila, Pilar; Montejo, Miguel; Len, Oscar; Torre-Cisneros, Julian; Carratalá, Jordi; Muñoz, Patricia; Fariñas, Carmen; Moreno, Asunción; Fresco, Gema; Goikoetxea, Josune; Gavaldá, Joan; Pozo, Juan Carlos; Bodro, Marta; Vena, Antonio; Casafont, Fernando; Cervera, Carlos; Silva, José Tiago; Aguado, José M

    2016-04-01

    Targeted prophylaxis has proven to be an efficient strategy in liver transplantation recipients (LTRs). The aim of this study was to compare the effectiveness and safety of caspofungin with that of fluconazole in high-risk (HR) LTRs. Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR-LTRs in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. During the study period (2005-2012), we analyzed 195 HR-LTRs from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole. Of a total of 17 (8.7%) global invasive fungal infections (IFIs), breakthrough IFIs accounted for 11 (5.6%) and invasive aspergillosis (IA) accounted for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFIs. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFIs (2.1% versus 9.2%, P = 0.04). In patients requiring dialysis (n = 62), caspofungin significantly reduced the frequency of breakthrough IFIs (P = 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction, 0.06; 95% confidence interval [CI], 0.001-0.11; P = 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. Caspofungin and fluconazole have similar efficacy for the prevention of global IFIs in HR-LTRs in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFIs and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR-LTRs, although bilirubin levels may be increased.

  9. Prophylaxis and therapy using liposomal amphotericin B (AmBisome) for invasive fungal infections in children undergoing organ or allogeneic bone-marrow transplantation.

    PubMed

    Ringdén, O; Andström, E E; Remberger, M; Dahllöf, G; Svahn, B M; Tollemar, J

    1997-11-01

    Sixty-one children with a median age of 6 years (range 1-16) were given prophylaxis/therapy for 78 courses of treatment with liposomal amphotericin (AmBisome) and were reviewed retrospectively. Thirty-six received allogeneic bone marrow, 22 a liver transplant, 2 kidneys and 1 a liver and kidney. AmBisome was given as prophylaxis in 30 episodes, as treatment for suspected invasive fungal infections (IFI) in 33 and for a verified IFI in 15. AmBisome prophylaxis was given for a median of 14 days in a dose of 1 mg/kg/day. The median dose of AmBisome was 2.1 mg/kg/day (range 0.9-5.0). The median duration of therapy was 10 days in children with suspected IFI and 20 days in children with verified IFI. The total dose ranged from 0.025 g up to a maximum of 3.95 g. Proven and probable side effects of AmBisome were a decrease in the level of serum potassium (30/78 cases), renal toxicity (22), an increase in the alkaline phosphatases (24), back pain (2), fever and abdominal pain (2), anaphylactic reaction (1), an increase in the bilirubin level (1), nausea (1), chest pain (1) and fever (1). Of 31 children with suspected IFI, fever disappeared in 21 (68%). In 14 verified or suspected IFI cases treated for 5 days or more, the clinical cure rate was 12 (86%). Eradication of fungi from a deep site was verified in 8/10 and the survival rate from 1 1/2 years to more than 7 years was 7/12 (58%). We conclude that AmBisome was well tolerated as prophylaxis and therapy in transplanted children, few acute toxic side effects were seen and the cure rate in verified IFI was high.

  10. Tolerability and outcome of once weekly liposomal amphotericin B for the prevention of invasive fungal infections in hematopoietic stem cell transplant patients with graft-versus-host disease

    PubMed Central

    Tran, H. Luu; Mahmoudjafari, Zahra; Rockey, Michelle; Henry, Dave; Grauer, Dennis; Aljitawi, Omar; Abhyankar, Sunil; Ganguly, Siddhartha; Lin, Tara; McGuirk, Joseph

    2015-01-01

    Background Invasive fungal infections remain problematic in immunosuppressed allogeneic stem cell transplant recipients and the use of corticosteroids for the treatment of graft-versus-host-disease can increase the risk three-fold. Although antifungal prophylaxis has been shown to decrease the incidence of infection, the optimal antifungal prophylactic regimen in this patient population has yet to be identified. Since early diagnosis of fungal infections might not be possible and the treatment of established fungal infections might be difficult and associated with high infection related mortality, prevention has become an important strategy in reducing overall morbidity and mortality. While triazoles are the preferred agents, some patients are unable to tolerate them and an alternative drug is warranted. Objectives To assess the tolerability of once weekly liposomal amphotericin B as a prophylactic strategy in patients undergoing stem cell transplantation by evaluating any adverse events leading to its discontinuation. In terms of efficacy, to also compare the outcome and incidence of invasive fungal infections in patients who received amphotericin B, triazoles, and echinocandins. Results A total of 101 allogeneic transplant recipients receiving corticosteroids for the treatment of graft-versus-host-disease and antifungal prophylaxis were evaluated from August 2009 to September 2012. Liposomal amphotericin B 3 mg/kg intravenous once weekly was found to be well-tolerated. The incidence of invasive fungal infections was 19%, 17%, and 7% in the liposomal amphotericin B, echinocandin, and triazole groups, respectively. Two deaths occurred in the liposomal amphotericin B group and one death occurred in the echinocandin group. None of the deaths were fungal infection-related. Conclusion Antifungal prophylaxis with liposomal amphotericin B was well-tolerated but the incidence of invasive fungal infections in patients receiving liposomal amphotericin B was higher than

  11. Effects of the Epichloë fungal endophyte symbiosis with Schedonorus pratensis on host grass invasiveness.

    PubMed

    Shukla, Kruti; Hager, Heather A; Yurkonis, Kathryn A; Newman, Jonathan A

    2015-07-01

    Initial studies of grass-endophyte mutualisms using Schedonorus arundinaceus cultivar Kentucky-31 infected with the vertically transmitted endophyte Epichloë coenophiala found strong, positive endophyte effects on host-grass invasion success. However, more recent work using different cultivars of S. arundinaceus has cast doubt on the ubiquity of this effect, at least as it pertains to S. arundinaceus-E. coenophiala. We investigated the generality of previous work on vertically transmitted Epichloë-associated grass invasiveness by studying a pair of very closely related species: S. pratensis and E. uncinata. Seven cultivars of S. pratensis and two cultivars of S. arundinaceus that were developed with high- or low-endophyte infection rate were broadcast seeded into 2 × 2-m plots in a tilled, old-field grassland community in a completely randomized block design. Schedonorus abundance, endophyte infection rate, and co-occurring vegetation were sampled 3, 4, 5, and 6 years after establishment, and the aboveground invertebrate community was sampled in S. pratensis plots 3 and 4 years after establishment. Endophyte infection did not enable the host grass to achieve high abundance in the plant community. Contrary to expectations, high-endophyte S. pratensis increased plant richness relative to low-endophyte cultivars. However, as expected, high-endophyte S. pratensis marginally decreased invertebrate taxon richness. Endophyte effects on vegetation and invertebrate community composition were inconsistent among cultivars and were weaker than temporal effects. The effect of the grass-Epichloë symbiosis on diversity is not generalizable, but rather specific to species, cultivar, infection, and potentially site. Examining grass-endophyte systems using multiple cultivars and species replicated among sites will be important to determine the range of conditions in which endophyte associations benefit host grass performance and have subsequent effects on co

  12. Effects of the Epichloë fungal endophyte symbiosis with Schedonorus pratensis on host grass invasiveness

    PubMed Central

    Shukla, Kruti; Hager, Heather A; Yurkonis, Kathryn A; Newman, Jonathan A

    2015-01-01

    Initial studies of grass–endophyte mutualisms using Schedonorus arundinaceus cultivar Kentucky-31 infected with the vertically transmitted endophyte Epichloë coenophiala found strong, positive endophyte effects on host-grass invasion success. However, more recent work using different cultivars of S. arundinaceus has cast doubt on the ubiquity of this effect, at least as it pertains to S. arundinaceus–E. coenophiala. We investigated the generality of previous work on vertically transmitted Epichloë-associated grass invasiveness by studying a pair of very closely related species: S. pratensis and E. uncinata. Seven cultivars of S. pratensis and two cultivars of S. arundinaceus that were developed with high- or low-endophyte infection rate were broadcast seeded into 2 × 2-m plots in a tilled, old-field grassland community in a completely randomized block design. Schedonorus abundance, endophyte infection rate, and co-occurring vegetation were sampled 3, 4, 5, and 6 years after establishment, and the aboveground invertebrate community was sampled in S. pratensis plots 3 and 4 years after establishment. Endophyte infection did not enable the host grass to achieve high abundance in the plant community. Contrary to expectations, high-endophyte S. pratensis increased plant richness relative to low-endophyte cultivars. However, as expected, high-endophyte S. pratensis marginally decreased invertebrate taxon richness. Endophyte effects on vegetation and invertebrate community composition were inconsistent among cultivars and were weaker than temporal effects. The effect of the grass–Epichloë symbiosis on diversity is not generalizable, but rather specific to species, cultivar, infection, and potentially site. Examining grass–endophyte systems using multiple cultivars and species replicated among sites will be important to determine the range of conditions in which endophyte associations benefit host grass performance and have subsequent effects on

  13. Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

    PubMed Central

    2011-01-01

    Background To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case. Case Presentation A 9 year-old male with acute lymphoblastic leukemia complicated by pancytopenia and disseminated Intravascular coagulation was given platelet transfusion. He developed disseminated fusariosis and was referred to the ophthalmology team for right endogenous endophthalmitis. The infection was controlled with aggressive systemic and intravitreal antifungals. Conclusion Patients with acute lymphoblastic leukemia are predisposed to endogenous fungal endophthalmitis. Transfusion-associated immune modulation may further increase host susceptibility to such opportunistic infections. PMID:22044440

  14. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

    PubMed

    Segal, Brahm H; Herbrecht, Raoul; Stevens, David A; Ostrosky-Zeichner, Luis; Sobel, Jack; Viscoli, Claudio; Walsh, Thomas J; Maertens, Johan; Patterson, Thomas F; Perfect, John R; Dupont, Bertrand; Wingard, John R; Calandra, Thierry; Kauffman, Carol A; Graybill, John R; Baden, Lindsey R; Pappas, Peter G; Bennett, John E; Kontoyiannis, Dimitrios P; Cordonnier, Catherine; Viviani, Maria Anna; Bille, Jacques; Almyroudis, Nikolaos G; Wheat, L Joseph; Graninger, Wolfgang; Bow, Eric J; Holland, Steven M; Kullberg, Bart-Jan; Dismukes, William E; De Pauw, Ben E

    2008-09-01

    Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

  15. Pharmacoeconomic evaluation of caspofungin versus liposomal amphotericin B in empirical treatment of invasive fungal infections in Turkey.

    PubMed

    Turner, S J; Senol, E; Kara, A; Al-Badriyeh, D; Kong, D C M; Dinleyici, E C

    2013-09-01

    Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB.

  16. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation.

    PubMed

    van Burik, Jo-Anne H; Ratanatharathorn, Voravit; Stepan, Daniel E; Miller, Carole B; Lipton, Jeffrey H; Vesole, David H; Bunin, Nancy; Wall, Donna A; Hiemenz, John W; Satoi, Yoichi; Lee, Jeanette M; Walsh, Thomas J

    2004-11-15

    We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg of micafungin (1 mg/kg for patients weighing <50 kg) and 400 mg of fluconazole (8 mg/kg for patients weighing <50 kg) administered once per day. Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and as the absence of proven or probable IFI through the end of the 4-week period after treatment. The overall efficacy of micafungin was superior to that of fluconazole as antifungal prophylaxis during the neutropenic phase after HSCT (80.0% in the micafungin arm vs. 73.5% in the fluconazole arm [difference, 6.5%]; 95% confidence interval, 0.9%-12%; P=.03). This randomized trial demonstrates the efficacy of an echinocandin for antifungal prophylaxis in neutropenic patients.

  17. Challenges on non-invasive ventilation to treat acute respiratory failure in the elderly.

    PubMed

    Scala, Raffaele

    2016-11-15

    Acute respiratory failure is a frequent complication in elderly patients especially if suffering from chronic cardio-pulmonary diseases. Non-invasive mechanical ventilation constitutes a successful therapeutic tool in the elderly as, like in younger patients, it is able to prevent endotracheal intubation in a wide range of acute conditions; moreover, this ventilator technique is largely applied in the elderly in whom invasive mechanical ventilation is considered not appropriated. Furthermore, the integration of new technological devices, ethical issues and environment of treatment are still largely debated in the treatment of acute respiratory failure in the elderly.This review aims at reporting and critically analyzing the peculiarities in the management of acute respiratory failure in elderly people, the role of noninvasive mechanical ventilation, the potential advantages of applying alternative or integrated therapeutic tools (i.e. high-flow nasal cannula oxygen therapy, non-invasive and invasive cough assist devices and low-flow carbon-dioxide extracorporeal systems), drawbacks in physician's communication and "end of life" decisions. As several areas of this topic are not supported by evidence-based data, this report takes in account also "real-life" data as well as author's experience.The choice of the setting and of the timing of non-invasive mechanical ventilation in elderly people with advanced cardiopulmonary disease should be carefully evaluated together with the chance of using integrated or alternative supportive devices. Last but not least, economic and ethical issues may often challenges the behavior of the physicians towards elderly people who are hospitalized for acute respiratory failure at the end stage of their cardiopulmonary and neoplastic diseases.

  18. Invasive Trichosporon Infection: a Systematic Review on a Re-emerging Fungal Pathogen

    PubMed Central

    de Almeida Júnior, João N.; Hennequin, Christophe

    2016-01-01

    Objectives: This review aimed to better depict the clinical features and address the issue of therapeutic management of Trichosporon deep-seated infections. Methods: We comprehensively reviewed the cases of invasive Trichosporon infection reported in the literature from 1994 (date of taxonomic modification) to 2015. Data from antifungal susceptibility testing (AST) studies were also analyzed. Results: Two hundred and three cases were retained and split into four groups: homeopathy (n = 79), other immunodeficiency conditions (n = 41), miscellaneous (n = 58) and newborns (n = 25). Trichosporon asahii was the main causative species (46.7%) and may exhibit cross-resistance to different antifungal classes. The unfavorable outcome rate was at 44.3%. By multivariate analysis, breakthrough infection (OR 2.45) was associated with unfavorable outcome, whilst the use of an azole-based therapy improved the prognosis (OR 0.16). Voriconazole-based treatment was associated with favorable outcome in hematological patients (73.6 vs. 41.8%; p = 0.016). Compiled data from AST demonstrated that (i) T. asahii exhibits the highest MICs to amphotericin B and (ii) voriconazole has the best in vitro efficacy against clinical isolates of Trichosporon spp. Conclusions: Trichosporon infection is not only restricted to hematological patients. Analysis of compiled data from AST and clinical outcome support the use of voriconazole as first line therapy. PMID:27799926

  19. Performance of Panfungal- and Specific-PCR-Based Procedures for Etiological Diagnosis of Invasive Fungal Diseases on Tissue Biopsy Specimens with Proven Infection: a 7-Year Retrospective Analysis from a Reference Laboratory

    PubMed Central

    Bernal-Martinez, L.; Castelli, M. V.; Rodriguez-Tudela, J. L.; Cuenca-Estrella, M.

    2014-01-01

    A retrospective analysis of real-time PCR (RT-PCR) results for 151 biopsy samples obtained from 132 patients with proven invasive fungal diseases was performed. PCR-based techniques proved to be fast and sensitive and enabled definitive diagnosis in all cases studied, with detection of a total of 28 fungal species. PMID:24574295

  20. Fungal Sinusitis

    MedlinePlus

    ... presence of large granules that attract the reddish-orange eosin stain) to attack fungi, and the eosinophils irritate the membranes in the nose. As long as fungi remain, so will the irritation. Chronic Indolent Sinusitis is an invasive form of fungal sinusitis in ...

  1. Hypoxia inducible factor-1α regulates a pro-invasive phenotype in acute monocytic leukemia

    PubMed Central

    Migliavacca, Jessica; Percio, Stefano; Valsecchi, Roberta; Ferrero, Elisabetta; Spinelli, Antonello; Ponzoni, Maurilio; Tresoldi, Cristina; Pattini, Linda

    2016-01-01

    Hypoxia inducible transcription factors (HIFs) are the main regulators of adaptive responses to hypoxia and are often activated in solid tumors, but their role in leukemia is less clear. In acute myeloid leukemia (AML), in particular, controversial new findings indicate that HIF-1α can act either as an oncogene or a tumor suppressor gene, and this may depend on the stage of leukemia development and/or the AML sub-type. In this study, we find that HIF-1α promotes leukemia progression in the acute monocytic leukemia sub-type of AML through activation of an invasive phenotype. By applying a list of validated HIF-1α-target genes to different AML sub-types, we identified a HIF-1α signature that typifies acute monocytic leukemia when compared with all other AML sub-types. We validated expression of this signature in cell lines and primary cells from AML patients. Interestingly, this signature is enriched for genes that control cell motility at different levels. As a consequence, inhibiting HIF-1α impaired leukemia cell migration, chemotaxis, invasion and transendothelial migration in vitro, and this resulted in impaired bone marrow homing and leukemia progression in vivo. Our data suggest that in acute monocytic leukemia an active HIF-1α-dependent pro-invasive pathway mediates the ability of leukemic cells to migrate and invade extramedullary sites and may be targeted to reduce leukemia dissemination. PMID:27447550

  2. Acute upper thermal limits of three aquatic invasive invertebrates: hot water treatment to prevent upstream transport of invasive species.

    PubMed

    Beyer, Jessica; Moy, Philip; De Stasio, Bart

    2011-01-01

    Transport of aquatic invasive species (AIS) by boats traveling up rivers and streams is an important mechanism of secondary spread of AIS into watersheds. Because physical barriers to AIS movement also prevent navigation, alternate methods for preventing spread are necessary while allowing upstream navigation. One promising approach is to lift boats over physical barriers and then use hot water immersion to kill AIS attached to the hull, motor, or fishing gear. However, few data have been published on the acute upper thermal tolerance limits of potential invaders treated in this manner. To test the potential effectiveness of this approach for a planned boat lift on the Fox River of northeastern WI, USA, acute upper thermal limits were determined for three AIS, adult zebra mussels (Dreissena polymorpha), quagga mussels (Dreissena rostriformis bugensis), and spiny water fleas (Bythotrephes longimanus) from the local area employing temperatures from 32 to 54°C and immersion times from 1 to 20 min. Mortality was determined after immersion followed by a 20-min recovery period. Immersion at 43°C for at least 5 min was required to ensure 100% mortality for all three species, but due to variability in the response by Bythotrephes a 10 min immersion would be more reliable. Overall there were no significant differences between the three species in acute upper thermal limits. Heated water can be an efficient, environmentally sound, and cost effective method of controlling AIS potentially transferred by boats, and our results should have both specific and wide-ranging applications in the prevention of the spread of aquatic invasive species.

  3. Acute Upper Thermal Limits of Three Aquatic Invasive Invertebrates: Hot Water Treatment to Prevent Upstream Transport of Invasive Species

    NASA Astrophysics Data System (ADS)

    Beyer, Jessica; Moy, Philip; de Stasio, Bart

    2011-01-01

    Transport of aquatic invasive species (AIS) by boats traveling up rivers and streams is an important mechanism of secondary spread of AIS into watersheds. Because physical barriers to AIS movement also prevent navigation, alternate methods for preventing spread are necessary while allowing upstream navigation. One promising approach is to lift boats over physical barriers and then use hot water immersion to kill AIS attached to the hull, motor, or fishing gear. However, few data have been published on the acute upper thermal tolerance limits of potential invaders treated in this manner. To test the potential effectiveness of this approach for a planned boat lift on the Fox River of northeastern WI, USA, acute upper thermal limits were determined for three AIS, adult zebra mussels ( Dreissena polymorpha), quagga mussels ( Dreissena rostriformis bugensis), and spiny water fleas ( Bythotrephes longimanus) from the local area employing temperatures from 32 to 54°C and immersion times from 1 to 20 min. Mortality was determined after immersion followed by a 20-min recovery period. Immersion at 43°C for at least 5 min was required to ensure 100% mortality for all three species, but due to variability in the response by Bythotrephes a 10 min immersion would be more reliable. Overall there were no significant differences between the three species in acute upper thermal limits. Heated water can be an efficient, environmentally sound, and cost effective method of controlling AIS potentially transferred by boats, and our results should have both specific and wide-ranging applications in the prevention of the spread of aquatic invasive species.

  4. Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

    PubMed

    Zhao, Ying Jiao; Khoo, Ai Leng; Tan, Gloria; Teng, Monica; Tee, Caroline; Tan, Ban Hock; Ong, Benjamin; Lim, Boon Peng; Chai, Louis Yi Ann

    2015-11-02

    Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care

  5. Impact of CYP2C19 genetic polymorphisms on voriconazole dosing and exposure in adult patients with invasive fungal infections.

    PubMed

    Lamoureux, Fabien; Duflot, Thomas; Woillard, Jean-Baptiste; Metsu, David; Pereira, Tony; Compagnon, Patricia; Morisse-Pradier, Hélène; El Kholy, Mona; Thiberville, Luc; Stojanova, Jana; Thuillez, Christian

    2016-02-01

    Voriconazole (VCZ) use is limited by its narrow therapeutic range and significant interpatient variability in exposure. This study aimed to assess (i) the impact of CYP2C19 genotype on VCZ exposure and (ii) the doses required to achieve the therapeutic range in adult patients with invasive fungal infections (IFIs). Therapeutic drug monitoring (TDM) of VCZ, based on trough concentration measurement, and CYP2C19 genotyping were used to guide VCZ dosing in Caucasian patients with IFIs. The two common polymorphisms in Caucasians (CYP2C19*2 and *17), associated with decreased or increased CYP2C19 activity, respectively, were correlated with the daily VCZ dose, pharmacokinetic parameters and concentration-to-dose ratio. In total, 111 trough concentration measurements from 35 genotyped patients were analysed using linear mixed-effect models. The mean VCZ doses required to achieve target concentrations were significantly higher in CYP2C19*17 carriers compared with CYP2C19*1/*1 individuals (P<0.001): 2.57±0.25mg/kg twice daily in CYP2C19*1/*1 patients versus 3.94±0.39mg/kg and 6.75±0.54mg/kg in *1/*17 and *17/*17 patients, respectively. In addition, exposure to VCZ correlated with the CYP2C19*17 variant. Indices of exposure for CYP2C19*2 carriers were in line with the functional effect of this polymorphism compared with CYP2C19*1/*1 individuals, however comparisons of doses required to achieve target concentrations were not statistically different. The CYP2C19*17 allele predicted both VCZ exposure and dose required to achieve effective and non-toxic concentrations. CYP2C19 genotyping appears useful to guide VCZ initial dosing when coupled with TDM and to explain subtherapeutic concentrations frequently observed in clinical practice.

  6. [Reflections on the use of non-invasive mechanical ventilation in acute respiratory failure].

    PubMed

    Scala, Raffaele

    2012-12-01

    Given its prevalence into the clinical practice, non-invasive ventilation (NIV) can be included among the cornerstones of medicine. Just think of the acute applications of NIV which are in constant expansion, from COPD exacerbation to severe de novo hypoxemia, from postoperative distress to extra-hospital use in acute pulmonary edema, from ongoing support of interventional procedures to delicate strategies for end of life in terminally ill oncologic and non-oncologic patients. The thought should be focused on how, by whom, where and to whom is delivered this mode of artificial ventilation to avoid the risk of trivialization and flattening.

  7. [Recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the prevention of invasive fungal infection due to filamentous fungi].

    PubMed

    Ruiz-Camps, Isabel; Aguado, Jose María; Almirante, Benito; Bouza, Emilio; Ferrer Barbera, Carmen; Len, Oscar; López-Cerero, Lorena; Rodríguez-Tudela, Juan Luis; Ruiz, Miguel; Solé, Amparo; Vallejo, Carlos; Vázquez, Lourdes; Zaragoza, Rafael; Cuenca-Estrella, Manuel

    2010-03-01

    Invasive fungal infections (IFI) due to filamentous fungi still have high rates of mortality associated with the difficulties of early detection of the infection and their therapeutic limitations. Consequently, a useful approach is to prevent patients at risk of fungal infection from getting in contact with conidia of Aspergillus and other mould species. This document describes the recommendations to prevent IFI due to filamentous fungi, prepared by Spanish experts from different medical and professional fields. The paper reviews the incidence of the IFI in different risk populations and the questions related to environmental measures of prevention, control of hospital infections, additional procedures for prevention, prevention of IFI outside hospitals, as well as antifungal prophylaxis.

  8. Outcomes of minimally-invasive temporary RVAD support for acute right ventricular failure during minimally-invasive LVAD implantation.

    PubMed

    Schaefer, Andreas; Reichart, Daniel; Bernhardt, Alexander M; Kubik, Mathias; Barten, Markus J; Wagner, Florian M; Reichenspurner, Hermann; Philipp, Sebastian A; Deuse, Tobias

    2017-01-20

    Right ventricular failure (RVF) may still occur despite the benefits of minimally-invasive left ventricular assist device (MI-LVAD) implantation. Our center strategy aims to avoid aggressive postoperative inotrope use by utilizing mechanical support to facilitate RV recovery and adaptation. We herein report first outcomes of patients with minimally-invasive temporary right ventricular assist device (MI-t-RVAD) support for RVF during MI-LVAD implantation.RVF was defined as requiring more than moderate inotopic support after weaning from cardiopulmonary bypass according to INTERMACS adverse event definitions. All patients requiring MI-t-RVAD support for RVF during MI-LVAD implantation between 01/2012 and 04/2016 were retrospectively reviewed. Clinical endpoints were death or unsuccessful RVAD weaning.Overall 10 patients (90% male, mean age 49.6±14.8 years) underwent MI-t-RVAD implantation. Duration of MI-t-RVAD support was 16.2±11.6 days. RVAD weaning and subsequent uneventful awake device explantation was successful in all cases. The 30-day survival was 80%.Our results confirm safety and feasibility of MI-t-RVAD support for acute RVF in the setting of MI-LVAD implantation. The potential benefits of this strategy are more stable hemodynamics in the first postoperative days that usually are crucial for LVAD patients and reduced inotrope requirement.

  9. Non-invasive ventilation in chronic obstructive pulmonary disease: management of acute type 2 respiratory failure.

    PubMed

    Roberts, C M; Brown, J L; Reinhardt, A K; Kaul, S; Scales, K; Mikelsons, C; Reid, K; Winter, R; Young, K; Restrick, L; Plant, P K

    2008-10-01

    Non-invasive ventilation (NIV) in the management of acute type 2 respiratory failure in patients with chronic obstructive pulmonary disease (COPD) represents one of the major technical advances in respiratory care over the last decade. This document updates the 2002 British Thoracic Society guidance and provides a specific focus on the use of NIV in COPD patients with acute type 2 respiratory failure. While there are a variety of ventilator units available most centres now use bi-level positive airways pressure units and this guideline refers specifically to this form of ventilatory support although many of the principles encompassed are applicable to other forms of NIV. The guideline has been produced for the clinician caring for COPD patients in the emergency and ward areas of acute hospitals.

  10. Effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection

    PubMed Central

    Zhang, Yu; Gu, Fang; Wang, Fengxian; Zhang, Yuanda

    2016-01-01

    Objective: To evaluate the effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection. Methods: A total of 120 patients with burn-induced invasive fungal infection were randomly divided into an early enteral nutrition (EN) group and a parenteral nutrition (PN) group (n=60). The patients were given nutritional support intervention for 14 days, and the expression levels of serum transferrin, albumin, total protein, endotoxin, D-lactic acid and inflammatory cytokines were detected on the 1st, 7th and 14th days respectively. Results: As the treatment progressed, the levels of serum transferrin, albumin and total protein of the EN group were significantly higher than those of the PN group (P<0.05), while the levels of serum endotoxin and D-lactic acid of the form group were significantly lower (P<0.05). After treatment, the expression levels of IL-6 and TNF-α were decreased in the EN group, which were significantly different from those of the PN group (P<0.05). During treatment, the incidence rates of complications such as abdominal distension, diarrhea, sepsis, nausea, vomiting and gastric retention were similar. The mean healing time of wound surface was 9.34±0.78 days in the EN group and 12.46±2.19 days in the PN group, i.e. such time of the former was significantly shorter than that of the latter (P<0.05). Conclusion: Treating patients having burn-induced invasive fungal infection by early enteral nutrition support with arginine can safely alleviate malnutrition and stress reaction, strengthen cellular immune function and promote wound healing, thereby facilitating the recovery of gastrointestinal motility and the function of intestinal mucosal barrier. PMID:27375697

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

    PubMed Central

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

    2009-01-01

    This single-center observational prospective study evaluated the performance of (1→3)-β-d-glucan as an adjunct diagnostic tool in 12 patients with proven invasive fungal disease with different risk factors. The infections were due to either uncommon fungal pathogens such as dematiaceous molds (Scedosporium apiospermum, Alternaria infectoria, and Cladosporium macrocarpum) and hyaline septate molds (Fusarium solani and Blastoschizomyces capitatus) or Aspergillus spp. with unusual clinical presentations. PMID:19158282

  12. Urinalysis for interleukin-8 in the non-invasive diagnosis of acute and chronic inflammatory diseases

    PubMed Central

    Taha, A; Grant, V; Kelly, R

    2003-01-01

    Background and aims: Given its role in mediating inflammation, the use of urinary interleukin-8 (IL-8) was assessed in the non-invasive diagnosis of acute and chronic inflammatory diseases. Methods: IL-8 was measured by an enzyme linked immunosorbent assay in random urine samples (1 ml each) carrying code numbers and taken from 208 patients: 177 adults and 31 children presenting with a range of active or inactive inflammatory conditions. Results: In the appropriate controls and in patients with inactive inflammation, the median urinary IL-8 levels ranged from 7–12 pg/ml, compared with 104 pg/ml in active ulcerative colitis (p = 0.002), 54 in active Crohn's disease (p = 0.025), 93 in active rheumatoid arthritis (p = 0.001), 107 in acute cholecystitis (p<0.0001), 127 in acute appendicitis (p = 0.0001), and 548 pg/ml in urinary tract infection (p<0.0001). Children with non-viral inflammation/infection also had higher IL-8 values (median, 199 pg/ml; p = 0.0001) than those with viral infection (median, 7 pg/ml) or non-specific conditions (median, 10 pg/ml). In the study group as a whole urinary IL-8 values correlated positively with peripheral blood white cell count (r = 0.32; p < 0.001), erythrocyte sedimentation rate (r = 0.41; p<0.001), and C-reactive protein (r = 0.33; p<0.001). Conclusion: Taking the appropriate clinical situation into account, urinary IL-8 measurement helps in the non-invasive assessment of active inflammation in at least a number of common acute and chronic conditions. PMID:12697917

  13. Combination therapy with caspofungin and liposomal amphotericin B for invasive aspergillosis.

    PubMed

    Elanjikal, Ziju; Sörensen, Jan; Schmidt, Helga; Dupuis, Wolfgang; Tintelnot, Kathrin; Jautzke, Günter; Klingebiel, Thomas; Lehrnbecher, Thomas

    2003-07-01

    Ina 24-month-old girl with acute lymphoblastic leukemia and invasive aspergillosis, only combination therapy with liposomal amphotericin B and caspofungin achieved a good response. Combination therapy could be a useful treatment option in children with invasive fungal disease, but before it can be routinely recommended, carefully controlled in vivo studies and well-designed randomized clinical trials are needed.

  14. Comparison of Three Distinct Prophylactic Agents Against Invasive Fungal Infections in Patients Undergoing Haplo-identical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

    PubMed Central

    El-Cheikh, Jean; Crocchiolo, Roberto; Vai, Andrea; Furst, Sabine; Bramanti, Stefania; Sarina, Barbara; Granata, Angela; Faucher, Catherine; Mohty, Bilal; Harbi, Samia; Bouabdallah, Reda; Vey, Norbert; Santoro, Armando; Chabannon, Christian; Castagna, Luca; Blaise, Didier

    2015-01-01

    Over the past decade, invasive fungal infections (IFIs) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to bedetermined. We conducted a retrospective analysis, comparing the safety and efficacy of micafungin 50mg/day vs. fluconazole 400mg/day vs. itraconazole 200mg/day as prophylaxis for adult patients with various haematological diseases receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) followed by high-dose cyclophosphamide (PT-Cy). Overall, 99 patients were identified: 30 patients received micafungin, 50 and 19 patients received itraconazole and fluconazole, respectively. After a median follow-up of 12 months (range: 1–51), proven or probable IFIs were reported in 3 patients (10%) in the micafungin, 5 patients in the itraconazole (10%) and 2 patients (11%) in the fluconazole group (p=0.998). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 3 [6%] in the itraconazole vs. 2 [11%] in the fluconazole group, p=0.589). Four patients (13%) in the micafungin group vs 13 (26%) patients in the itraconazole group and 10 (53%) patients in the fluconazole received empirical antifungal therapy (P = 0.19). No serious adverse events related to treatment were reported by patients, and there was no treatment discontinuation because of drug-related adverse events in both groups. The present analysis shows that micafungin did better than fluconazole in preventing invasive aspergillosis after transplant in these high-risk hematological diseases, as expected. In addition, micafungin was more effective than itraconazole in preventing all IFI episodes when also considering possible fungal infections. Future prospective studies would shed light on this issue, concerning this increasingly used transplant platform. PMID:26401237

  15. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients.

    PubMed

    Marchetti, O; Lamoth, F; Mikulska, M; Viscoli, C; Verweij, P; Bretagne, S

    2012-06-01

    As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); β-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.

  16. Epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study.

    PubMed

    Koehler, Philipp; Hamprecht, Axel; Bader, Oliver; Bekeredjian-Ding, Isabelle; Buchheidt, Dieter; Doelken, Gottfried; Elias, Johannes; Haase, Gerhard; Hahn-Ast, Corinna; Karthaus, Meinolf; Kekulé, Alexander; Keller, Peter; Kiehl, Michael; Krause, Stefan W; Krämer, Carolin; Neumann, Silke; Rohde, Holger; La Rosée, Paul; Ruhnke, Markus; Schafhausen, Philippe; Schalk, Enrico; Schulz, Katrin; Schwartz, Stefan; Silling, Gerda; Staib, Peter; Ullmann, Andrew; Vergoulidou, Maria; Weber, Thomas; Cornely, Oliver A; Vehreschild, Maria J G T

    2017-02-01

    Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently.

  17. Development, clinical utility, and place in therapy of posaconazole for prevention and treatment of invasive fungal infections

    PubMed Central

    Zoller, Emily; Valente, Connie; Baker, Kyle; Klepser, Michael E

    2010-01-01

    Posaconazole is an extended-spectrum azole antifungal that exhibits activity against a broad range of fungal pathogens, including yeasts and moulds. Clinical data have demonstrated the clinical utility of posaconazole against many therapy-refractory pathogens, including Aspergillus spp, Fusarium spp, and Zygomycetes. These data have provided clinicians with hope in these difficult situations. Some of the limitations that have emerged with the use of posaconazole are the lack of an intravenous formulation and erratic drug absorption. This fact is further complicated by the existence of saturable posaconazole absorption. Despite these drawbacks, posaconazole appears poised to become a prominent therapeutic modality for the prophylaxis and management of various fungal infections among high-risk patients. PMID:21116336

  18. Pathophysiological Basis of Acute Respiratory Failure on Non-Invasive Mechanical Ventilation.

    PubMed

    Romero-Dapueto, C; Budini, H; Cerpa, F; Caceres, D; Hidalgo, V; Gutiérrez, T; Keymer, J; Pérez, R; Molina, J; Giugliano-Jaramillo, C

    2015-01-01

    Noninvasive mechanical ventilation (NIMV) was created for patients who needed noninvasive ventilator support, this procedure decreases the complications associated with the use of endotracheal intubation (ETT). The application of NIMV has acquired major relevance in the last few years in the management of acute respiratory failure (ARF), in patients with hypoxemic and hypercapnic failure. The main advantage of NIMV as compared to invasive mechanical ventilation (IMV) is that it can be used earlier outside intensive care units (ICUs). The evidence strongly supports its use in patients with COPD exacerbation, support in weaning process in chronic obstructive pulmonary disease (COPD) patients, patients with acute cardiogenic pulmonary edema (ACPE), and Immunosuppressed patients. On the other hand, there is poor evidence that supports the use of NIMV in other pathologies such as pneumonia, acute respiratory distress syndrome (ARDS), and during procedures as bronchoscopy, where its use is still controversial because the results of these studies are inconclusive against the decrease in the rate of intubation or mortality.

  19. Pathophysiological Basis of Acute Respiratory Failure on Non-Invasive Mechanical Ventilation

    PubMed Central

    Romero-Dapueto, C; Budini, H; Cerpa, F; Caceres, D; Hidalgo, V; Gutiérrez, T; Keymer, J; Pérez, R; Molina, J; Giugliano-Jaramillo, C

    2015-01-01

    Noninvasive mechanical ventilation (NIMV) was created for patients who needed noninvasive ventilator support, this procedure decreases the complications associated with the use of endotracheal intubation (ETT). The application of NIMV has acquired major relevance in the last few years in the management of acute respiratory failure (ARF), in patients with hypoxemic and hypercapnic failure. The main advantage of NIMV as compared to invasive mechanical ventilation (IMV) is that it can be used earlier outside intensive care units (ICUs). The evidence strongly supports its use in patients with COPD exacerbation, support in weaning process in chronic obstructive pulmonary disease (COPD) patients, patients with acute cardiogenic pulmonary edema (ACPE), and Immunosuppressed patients. On the other hand, there is poor evidence that supports the use of NIMV in other pathologies such as pneumonia, acute respiratory distress syndrome (ARDS), and during procedures as bronchoscopy, where its use is still controversial because the results of these studies are inconclusive against the decrease in the rate of intubation or mortality. PMID:26312101

  20. Primary prophylaxis of invasive fungal diseases in allogeneic stem cell transplantation: revised recommendations from a consensus process by Gruppo Italiano Trapianto Midollo Osseo (GITMO).

    PubMed

    Girmenia, Corrado; Barosi, Giovanni; Piciocchi, Alfonso; Arcese, William; Aversa, Franco; Bacigalupo, Andrea; Bandini, Giuseppe; Bosi, Alberto; Busca, Alessandro; Castagnola, Elio; Caselli, Desiree; Cesaro, Simone; Ciceri, Fabio; Locasciulli, Anna; Locatelli, Franco; Mikulska, Malgorzata; Pagano, Livio; Prete, Arcangelo; Raiola, Anna Maria; Rambaldi, Alessandro

    2014-08-01

    This document updates and expands the recommendations on primary prophylaxis of invasive fungal diseases (IFD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, published in 2009 by the Gruppo Italiano Trapianto Midollo Osseo (GITMO). A consensus process was undertaken to describe and evaluate current information and practice regarding risk stratification and primary antifungal prophylaxis during the pre-engraftment and postengraftment phases after allo-HSCT. The revised recommendations were based on the evaluation of recent literature including a large, prospective, multicenter epidemiological study of allo-HSCT recipients conducted among the GITMO transplantation centers during the period of 2008 to 2010. It is intended as a guide for the identification of types and phases of transplantation at low, standard, and high risk for IFD, according to the underlying disease, transplantation, and post-transplantation factors. The risk stratification was the critical determinant of the primary antifungal approach for allo-HSCT recipients.

  1. Fungal Vaccines and Immunotherapeutics

    PubMed Central

    Santos, Evelyn; Levitz, Stuart M.

    2014-01-01

    Concomitant with the increased prevalence of immunocompromised persons, invasive fungal infections have become considerably more frequent in the last 50 years. High mortality rates caused by invasive mycoses and high morbidity because of intractable mucosal infections have created an unmet need for innovative prophylactic and therapeutic strategies against fungal pathogens. Several immunotherapeutics and vaccines are in development to address this need, although one has yet to reach the clinic. This review focuses on past and current immunotherapeutic and vaccine strategies being tested to either prevent or treat fungal infections, as well as the challenges associated with their development. PMID:25368016

  2. Multidisciplinary approach to the treatment of invasive fungal infections in adult patients. Prophylaxis, empirical, preemptive or targeted therapy, which is the best in the different hosts?

    PubMed Central

    Zaragoza, Rafael; Pemán, Javier; Salavert, Miguel; Viudes, Ángel; Solé, Amparo; Jarque, Isidro; Monte, Emilio; Romá, Eva; Cantón, Emilia

    2008-01-01

    The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients. PMID:19337433

  3. Relapsed acute lymphoblastic leukemia with unusual multiple bone invasions: A case report

    PubMed Central

    HANGAI, MAYUMI; WATANABE, KENTARO; SHIOZAWA, RYOSUKE; HIWATARI, MITSUTERU; IDA, KOHMEI; TAKITA, JUNKO

    2014-01-01

    The present study describes a unique pediatric case with multiple bone invasions of acute lymphoblastic leukemia (ALL) during remission. An eight-year-old male with a history of ALL was admitted complaining of intermittent and migrating pain in the limb 2 years following complete remission. Magnetic resonance imaging and whole-body positron emission tomography with 18F-fluorodeoxyglucose revealed abnormal multifocal involvement in the bones and corresponding soft tissues. Repeated bone marrow (BM) aspiration indicated normal cellular marrow without leukemic cells, and marked leukemic cell infiltration in different sections of the ilium, respectively. These findings suggested isolated bone relapse, and it is probable that systematic BM relapse occurred as a consequence. PMID:24944655

  4. Resistant ticks inhibit Metarhizium infection prior to haemocoel invasion by reducing fungal viability on the cuticle surface.

    PubMed

    Ment, Dana; Churchill, Alice C L; Gindin, Galina; Belausov, Eduard; Glazer, Itamar; Rehner, Stephen A; Rot, Asael; Donzelli, Bruno G G; Samish, Michael

    2012-06-01

    We studied disease progression of, and host responses to, four species in the Metarhizium anisopliae complex expressing green fluorescent protein (GFP). We compared development and determined their relative levels of virulence against two susceptible arthropods, the cattle tick Rhipicephalus annulatus and the lepidopteran Galleria mellonella, and two resistant ticks, Hyalomma excavatum and Rhipicephalus sanguineus. Metarhizium brunneum Ma7 caused the greatest mortality of R. annulatus, Metarhizium robertsii ARSEF 2575 and Metarhizium pingshaense PPRC51 exhibited intermediate levels of virulence, and Metarhizium majus PPRC27 caused low mortality of cattle ticks. Conidia of all four species germinated on all hosts examined, but on resistant hosts, sustained hyphal growth was inhibited and GFP emission steadily and significantly decreased over time, suggesting a loss of fungal viability. Cuticle penetration was observed only for the three most virulent species infecting susceptible hosts. Cuticles of resistant and susceptible engorged female ticks showed significant increases in red autofluorescence at sites immediately under fungal hyphae. This is the first report (i) of tick mortality occurring after cuticle penetration but prior to haemocoel colonization and (ii) that resistant ticks do not support development of Metarhizium germlings on the outer surface of the cuticle. Whether reduced Metarhizium viability on resistant tick cuticles is due to antibiosis or limited nutrient availability is unknown.

  5. Does High-Dose Cytarabine Cause More Fungal Infection in Patients With Acute Myeloid Leukemia Undergoing Consolidation Therapy: A Multicenter, Prospective, Observational Study in China.

    PubMed

    Wang, Ling; Hu, Jiong; Sun, Yuqian; Huang, He; Chen, Jing; Li, Jianyong; Ma, Jun; Li, Juan; Liang, Yingmin; Wang, Jianmin; Li, Yan; Yu, Kang; Hu, Jianda; Jin, Jie; Wang, Chun; Wu, Depei; Xiao, Yang; Huang, Xiaojun

    2016-01-01

    Invasive fungal infection (IFI) remains as a significant cause of morbidity and mortality in patients with acute myelogenous leukemia (AML). Here, we report the subgroup analysis of China Assessment of Antifungal Therapy in Haematological Disease (CAESAR) study to evaluate the risk of IFI in patients with AML in 1st remission receiving high-dose cytarabine (HiDAC) as consolidation. A total of 638 patients with AML in 1st complete remission were selected from the database. Among them, 130 patients received HiDAC alone with total dose of 2-3 g/m(2) × 6 while 508 patients received multiple-agent combination chemotherapy (multiagent chemo group). The patients' characteristics were generally not different but more patients in HiDAC group had peripherally inserted central catheter (61.5% vs 44.5%, P = 0.002). The median duration of neutropenia was 8.0 days in both HiDAC (2-20) and multiagent chemo group (2-28). Number of patients with prolonged neutropenia (>14 days) tended to be more in multiagent chemo group but not significant different (16.3% vs 8.8%, respectively). There was no significant difference between 2 groups in persistent neutropenic fever (40.8% vs 33.1%), antifungal treatment (11.5% vs 11.4%), and incidence of proven/probable IFI (4 probable in HiDAC vs 1 proven/4 probable in multiagent chemo, P = 0.35) or possible IFI. As to the clinical outcome in terms of duration of hospitalization and death in remission, there was a trend of shorter duration of hospitalization in HiDAC (19 days, 3-70) compare to multiagent chemo group (21 days, 1-367, P = 0.057) while no death documented in HiDAC group and only 2 patients died in the multiagent chemo group (0.4%). As to risk factors associated with IFI in all 638 patients, there was a trend of more IFI in patients with severe neutropenia (3.0%, P = 0.089) and previous history of IFI (3.85%, P = 0.086) while the antifungal prophylaxis was not associated significantly reduced IFI. Overall

  6. The role of surgery in the treatment of invasive fungal infection in paediatric haematology patients: a retrospective single-centre survey.

    PubMed

    Cesaro, Simone; Pegoraro, Anna; Tridello, Gloria; Pillon, Marta; Cannata, Elisa; Faggin, Stefano; Cecchetto, Giovanni

    2014-07-01

    Surgery may improve the control of fungal disease and patient survival. The aim of this study was to report a single-centre experience in using surgery for the treatment of paediatric invasive fungal infection (IFI). From 2001 to 2009, 18 paediatric onco-haematology patients underwent 24 surgical procedures as treatment of IFI. At surgery, severe thrombocytopenia and neutropenia were present in four and one episodes respectively. Complications were one pleural effusion, one pleural effusion and surgical wound infection, one pneumothorax with wound dehiscence and one wound dehiscence. None of them required repeat surgery. The median duration of hospitalisation for four complicated procedures was 11 days, range 3-16, and 7 days, range 2-13, for the 20 uncomplicated procedures. No surgery-related deaths occurred. Fourteen patients resumed chemotherapy after a median of 26 days, range 9-77, whereas nine patients underwent hematopoietic stem cell transplantation after a median of 42 days, range 27-110. At 3 months from IFI, 17 patients were alive (94%) and one patient (6%) died from mycosis; the 3-month overall survival (OS) being 94.4%, CI 66.6-99.2. After a median follow-up of 7.1 years (CI 2.8-7.5), the OS was 54.5%, CI 29.2-74.2. Surgery is a feasible and valuable option in paediatric patients because it is associated with a low incidence of complications and an acceptable delay in resuming the chemotherapeutic plan.

  7. Renal infarction secondary to invasive aspergillosis in a 5-year-old girl with acute lymphoblastic leukemia.

    PubMed

    Lee, Ju Hyun; Im, Soo Ah; Cho, Bin

    2014-07-01

    Aspergillus species have angioinvasive properties and can involve extrapulmonary organs by hematogenous spread from the lungs. However, renal involvement by Aspergillus is uncommon and is usually associated with the formation of abscesses. We report an unusual case of invasive renal aspergillosis presenting with extensive renal infarction in a 5-year-old girl with acute lymphoblastic leukemia. This case emphasizes the fact that renal aspergillosis initially presents with only renal infarction, and metastatic-embolism by invasive aspergillosis should be considered in differential diagnosis for any focal lesion of kidney in a patient with leukemia.

  8. Minimally Invasive Necrosectomy Techniques in Severe Acute Pancreatitis: Role of Percutaneous Necrosectomy and Video-Assisted Retroperitoneal Debridement

    PubMed Central

    Logue, Jennifer A.; Carter, C. Ross

    2015-01-01

    Consensus advocating a principle of early organ support, nutritional optimisation, followed ideally by delayed minimally invasive intervention within a “step-up” framework where possible has radically changed the surgical approach to complications of acute pancreatitis in the last 20 years. The 2012 revision of the Atlanta Classification incorporates these changes, and provides a background which underpins the complexities of individual patient management decisions. This paper discusses the place for delayed minimally invasive surgical intervention (percutaneous necrosectomy, video-assisted retroperitoneal debridement (VARD)), and the rationale for opting to adopt a percutaneous approach over endoscopic or laparoscopic approaches in different clinical situations. PMID:26587018

  9. Identification of fungal pathogens in a patient with acute myelogenic leukemia using a pathogen detection array technology

    PubMed Central

    Banerjee, Sagarika; Peck, Kristen N.; Feldman, Michael D.; Schuster, Mindy G.; Alwine, James C.; Robertson, Erle S.

    2016-01-01

    ABSTRACT Invasive zygomycosis in immunocompromised patients results in a high mortality rate, and early identification is crucial to optimize therapy and to reduce morbidity. However, diagnosing specific species of zygomycetes fungi possess challenge in the clinical laboratories. A need for a rapid and sensitive diagnostic tool for early recognition of a zygomycetes fungus in clinical samples to the species level will lead to prompt and accurate therapy and the PathoChip provides one such platform. We utilized a pathogen array technology referred to as PathoChip, comprised of oligonucleotide probes that can detect all the sequenced viruses as well as known pathogenic bacteria, fungi and parasites and family-specific conserved probes, thus providing a means for detecting previously uncharacterized members of a family. We rapidly identified a zygomycetous fungus, Rhizomucor pusillus, an otherwise challenge for the clinical laboratories, predominantly in a patient with acute myelogenous leukemia. This report highlights the value of PathoChip as a diagnostic tool to identify micro-organisms to the species level, especially for those difficult to identify in most clinical laboratories. It will also help clinicians to obtain a critical snapshot of the infection profile of a patient to plan treatment strategies. PMID:26619325

  10. A novel role for catalase B in the maintenance of fungal cell-wall integrity during host invasion in the rice blast fungus Magnaporthe grisea.

    PubMed

    Skamnioti, Pari; Henderson, Catherine; Zhang, Ziguo; Robinson, Zena; Gurr, Sarah Jane

    2007-05-01

    Asexual spores of the rice blast fungus germinate to produce a specialized and melanized infection structure, the appressorium, which is pivotal to successful plant penetration. To investigate whether Magnaporthe grisea counteracts the toxic burst of H2O2 localized beneath the site of attempted invasion, we examined the temporal expression of five candidate antioxidant genes. Of these, the putatively secreted large subunit catalase CATB gene was 600-fold up-regulated in vivo, coincident with penetration, and moderately up-regulated in vitro, in response to exogenous H2O2. Targeted gene replacement of CATB led to compromised pathogen fitness; the catB mutant displayed paler pigmentation and accelerated hyphal growth but lower biomass, poorer sporulation, fragile conidia and appressoria, and impaired melanization. The catB mutant was severely less pathogenic than Guy 11 on barley and rice, and its infectivity was further reduced on exposure to H2O2. The wild-type phenotype was restored by the reintroduction of CATB into the catB mutant We found no evidence to support a role for CATB in detoxification of the host-derived H2O2 at the site of penetration. Instead, we demonstrated that CATB plays a part in strengthening the fungal wall, a role of particular importance during forceful entry into the host.

  11. Association of mannose-binding lectin levels and invasive fungal disease in hematologic malignancy patients receiving myelosuppressive chemotherapy or allogeneic hematopoietic stem cell transplantation.

    PubMed

    Riwes, M M; Leather, H; Neal, D; Bennett, C; Sugrue, M; Cline, C; Stokes, J; Hiemenz, J; Hsu, J; Wingard, J R

    2016-09-01

    Several studies have suggested an association of mannose-binding lectin (MBL) deficiency with infections. In this study, we investigated the association between MBL deficiency and invasive fungal disease (IFD) in hematologic malignancy patients receiving myelosuppressive chemotherapy or hematopoietic stem cell transplant. MBL levels were quantified at the start of treatment in 152 patients who were followed for 6 months and scored as developing IFD or not. Forty-five patients (29.6%) developed IFD, of which 21 (46.7% of IFD cases and 13.8% of patients) were proven or probable IFD. Fifty-nine (38.8%) had MBL levels <1000 ng/mL. The rates of all IFD in patients with MBL levels below and above 1000 ng/mL were 33.9% and 26.9%, respectively (P=0.356). The rates of proven or probable IFD in patients with MBL levels below and above 1000 ng/mL were 11.9% and 15.1%, respectively (P=0.579). MBL levels <1000 ng/mL were not predictors of death (P=0.233). As expected, IFD was associated with death (P<0.0001). Our findings indicate that MBL levels <1000 ng/mL were not associated with an increased risk of developing IFD or overall survival.

  12. Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

    PubMed

    Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

    2016-02-05

    Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients.

  13. Invasive Candidiasis in Severe Acute Pancreatitis: Experience from a Tertiary Care Teaching Hospital

    PubMed Central

    Baronia, Arvind Kumar; Azim, Afzal; Ahmed, Armin; Gurjar, Mohan; Marak, Rungmei S. K.; Yadav, Reema; Sharma, Preeti

    2017-01-01

    Background: Invasive candidiasis (IC) is associated with increased morbidity in severe acute pancreatitis (SAP). There is limited information regarding the predisposing factors, Candida species distribution and in vitro susceptibility. Methodology: Current data have been derived from a larger prospective nonintervention study conducted on 200 critically ill patients which was done to study the antifungal prescription practices, collect epidemiological data, and perform an external validation of risk prediction models for IC under senior research associateship program of Council of Scientific and Industrial Research New Delhi. Of these critically ill patients, thirty had SAP and were included for analysis. Results: There were 23 males and 7 females. Out of eight patients (27%) who developed IC, three had isolated candidemia, two had isolated deep-seated candidiasis while three had both candidemia and deep-seated candidiasis. SAP patients with IC had a longer duration of Intensive Care Unit stay, hospital stay, days on mechanical ventilation and duration of shock. Mortality was not different between SAP patients with or without IC. Conclusion: There is a high rate of Candida infection in SAP. More studies are needed to generate epidemiological data and develop antifungal stewardship in this subset of high-risk population. PMID:28197050

  14. Fungal arthritis and osteomyelitis.

    PubMed

    Kohli, Rakhi; Hadley, Susan

    2005-12-01

    Fungal arthritis and osteomyelitis are uncommon diseases and generally present in an indolent fashion. The incidence of fungal bone and joint dis-ease is increasing with an increase in the prevalence of factors predisposing to invasive fungal disease, such as the use of central venous catheters, broad spectrum antibiotics, immunosuppression, and abdominal surgery. Definitive diagnosis relies on bone or synovial culture or biopsy. Successful management has traditionally consisted of amphotericin B in combination with surgical debridement. Given the rarity of this disease, treatment is not well defined, but reports of success with the use of azole antifungal agents, including itraconazole, fluconazole, voriconazole, and posaconazole, are promising.

  15. Minimally invasive flexor hallucis longus transfer in management of acute achilles tendon rupture associated with tendinosis: a case report.

    PubMed

    Lui, Tun Hing

    2012-04-01

    Chronic tendinopathy is characterized by pain in the tendon, generally at the start and completion of exercise. However, tendinosis may lead to decreased blood flow, increased stiffness of the tendon and reduced tensile strength, and predispose to rupture. Operative treatment is indicated to restore the function of the Achilles tendon and alleviate the prerupture heel cord pain. A case of acute Achilles tendon rupture with extensive tendinosis that was successfully treated with minimally invasive flexor hallucis longus transfer is reported.

  16. Ericaceous dwarf shrubs affect ectomycorrhizal fungal community of the invasive Pinus strobus and native Pinus sylvestris in a pot experiment.

    PubMed

    Kohout, Petr; Sýkorová, Zuzana; Bahram, Mohammad; Hadincová, Věroslava; Albrechtová, Jana; Tedersoo, Leho; Vohník, Martin

    2011-07-01

    This study aimed to elucidate the relationship between ericaceous understorey shrubs and the diversity and abundance of ectomycorrhizal fungi (EcMF) associated with the invasive Pinus strobus and native Pinus sylvestris. Seedlings of both pines were grown in mesocosms and subjected to three treatments simulating different forest microhabitats: (a) grown in isolation and grown with (b) Vaccinium myrtillus or (c) Vaccinium vitis-idaea. Ericaceous plants did not act as a species pool of pine mycobionts and inhibited the ability of the potentially shared species Meliniomyces bicolor to form ectomycorrhizae. Similarly, Ericaceae significantly reduced the formation of Thelephora terrestris ectomycorrhizae in P. sylvestris. EcMF species composition in the mesocosms was strongly affected by both the host species and the presence of an ericaceous neighbour. When grown in isolation, P. strobus root tips were predominantly colonised by Wilcoxina mikolae, whereas those of P. sylvestris were more commonly colonised by Suillus and Rhizopogon spp. Interestingly, these differences were less evident (Suillus + Rhizopogon spp.) or absent (W. mikolae) when the pines were grown with Ericaceae. P. strobus exclusively associated with Rhizopogon salebrosus s.l., suggesting the presence of host specificity at the intrageneric level. Ericaceous plants had a positive effect on colonisation of P. strobus root tips by R. salebrosus s.l. This study demonstrates that the interaction of selective factors such as host species and presence of ericaceous plants may affect the realised niche of the ectomycorrhizal fungi.

  17. Non-invasive mechanical ventilation in the treatment of acute respiratory failure in chronic obstructive pulmonary disease.

    PubMed

    Ambrosino, N; Nava, S; Rubini, F

    1993-01-01

    Acute respiratory failure is usually managed by means of mechanical ventilation via an endotracheal tube or tracheostomy, when conservative treatment fails. Invasive mechanical ventilation is associated with several complications. The recent development of non-invasive methods of ventilation, has led to an attempt to avoid the complications of invasive mechanical ventilation during episodes of acute respiratory failure, ensuring at the same time a similar degree of efficacy. Both intermittent negative pressure ventilation and positive pressure ventilation by face or nasal mask have recently been used for this purpose. Negative pressure ventilation by means of iron lung, cuirass or poncho-wrap ventilators, has never been used in place of endotracheal intubation, and studies of this kind of ventilation are inconclusive: as a consequence, there is, at the moment, no indication for the generalized use of negative pressure ventilation in acute respiratory failure. Intermittent positive pressure ventilation by facial or nasal masks, has recently been used in the treatment of respiratory failure in place of endotracheal intubation. The results are promising, but remain controversial. It may be attempted in selected patients with obstructive respiratory disorders, but the procedure is very time-consuming for nurses.

  18. Diagnostic Values and Limitations of (1,3)-β-D-Glucans and Galactomannan Assays for Invasive Fungal Infection in Patients Admitted to Pediatric Intensive Care Unit.

    PubMed

    Zheng, Fang; Zha, Hui; Yang, Dandan; Deng, Jun; Zhang, Zhiquan

    2017-04-01

    The relationship among (1,3)-β-D-glucans (BG), galactomannan (GM), and the risk of developing invasive fungal infections (IFI) has been observed in adult ICU and in children with hematological malignancies. Only scant data evaluated the value of BG/GM assays for diagnosis of IFI in patients with nonhematological diseases in pediatric intensive care unit (PICU). In this study, we assessed the diagnostic value of these markers for IFI in PICU. The records of 230 patients were retrospectively evaluated. Out of 117 patients (7 proven, 23 probable, and 87 cases without evidence of IFI) performed GM and BG assays. The results showed many factors were associated with false-positive test results. Patients who aged over 3 years had higher levels of GM and BG than younger infants. The levels of BG were higher in subjects with dairy, human blood products, antibiotics, and corticosteroids therapy than in cases without these treatments. Unlike BG assay, GM assay was less susceptible to above-mentioned factors expect blood products. The levels of BG and GM in IFI cases were dramatically higher than in controls. The diagnostic performance of these assays showed that GM assay had better results when compared with BG assay. On the whole, negative predictive value in both GM and BG assays was dramatically higher than other diagnostic parameters. In conclusion, BG assay was highly susceptible to many factors, and GM assay could be useful for diagnosis of IFI for its high sensitivity, but the over benefit of this assay limited in its inadequate specificity. The comparative advantage of BG and BG assays lied in excluding IFI in non-hematological PICU patients.

  19. Phase 1B study of the pharmacokinetics and safety of posaconazole intravenous solution in patients at risk for invasive fungal disease.

    PubMed

    Maertens, Johan; Cornely, Oliver A; Ullmann, Andrew J; Heinz, Werner J; Krishna, Gopal; Patino, Hernando; Caceres, Maria; Kartsonis, Nicholas; Waskin, Hetty; Robertson, Michael N

    2014-07-01

    This was a phase 1B, dose-ranging, multicenter, pharmacokinetics, and safety study of cyclodextrin-based posaconazole intravenous (i.v.) solution administered through a central line to subjects at high risk for invasive fungal disease (part 1 of a 2-part study [phase 1B/3]). Initially, the safety and tolerability of single-dose posaconazole i.v. 200 mg (n = 10) were compared with those of a placebo (n = 11). Subsequently, 2 doses were evaluated, posaconazole i.v. 200 mg once daily (q.d.) (n = 21) and 300 mg q.d. (n = 24). The subjects received twice-daily (b.i.d.) posaconazole i.v. on day 1, followed by 13 days of posaconazole i.v. q.d., then 14 days of posaconazole oral suspension 400 mg b.i.d. The steady-state (day 14) exposure target (average concentration [areas under concentration-time curve {AUCs}/24 h, average concentrations at steady state {Cavgs}], of ≥ 500 to ≤ 2,500 ng/ml in ≥ 90% of the subjects) was achieved by 94% of the subjects for 200 mg posaconazole q.d. and by 95% of subjects for 300 mg posaconazole q.d. The desired exposure target (mean steady-state Cavg, ∼ 1,200 ng/ml) was 1,180 ng/ml in the 200-mg dosing cohort and was exceeded in the 300-mg dosing cohort (1,430 ng/ml). Posaconazole i.v. was well tolerated. Posaconazole i.v. 300 mg q.d. was selected for the phase 3 study segment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01075984.).

  20. Granulocyte Macrophage Colony-Stimulating Factor in 66 Patients with Myeloid or Lymphoid Neoplasms and Recipients of Hematopoietic Stem Cell Transplantation with Invasive Fungal Disease

    PubMed Central

    Safdar, Amar; Rodriguez, Gilhen; Zuniga, Jorge; Akhrass, Fadi Al; Georgescu, Georgia; Pande, Anupam

    2013-01-01

    Background/Aims Adding granulocyte macrophage colony-stimulating factor (GM-CSF) may improve the response to antifungal therapy in immunosuppressed patients with invasive fungal disease (IFD). Methods We retrospectively assessed 66 patients in whom GM-CSF was given during antifungal therapy. Results Severe neutropenia (77%) and refractory/relapsed cancer (65%) were common in the group. Prior to GM-CSF therapy, 15% of patients received high-dose corticosteroids for a median of 30 ± 16 days (median cumulative dose [c.d.], 1184 ± 1019 mg), and 9 received steroids during GM-CSF therapy for a median of 16 ± 12 days (median c.d., 230 ± 1314 mg). Mild toxic effects were noted in 9% of patients; there were no cases of cardiopulmonary toxicity. All cause deaths were observed in 68% and 48% of patients died of progressive IFD. High-dose corticosteroids prior to GM-CSF (OR, 24; 95% CI, 2.21–264.9; P ≤ 0.009), GM-CSF started in the intensive care unit (OR, 10; 95% CI, 1.66–63.8; P ≤ 0.01), concurrent granulocyte transfusions (OR, 5; 95% CI, 1.27–16.8; P ≤ 0.02), and proven/probable IFD (OR, 4; 95% CI, 1–16.2; P ≤ 0.05) predicted antifungal treatment failure. Conclusions GM-CSF adjuvant therapy was tolerated without serous toxicity and antifungal treatment failure remained a challenge in patients treated with high-dose systemic corticosteroids. PMID:23038157

  1. Triazole antifungals used for prophylaxis and treatment of invasive fungal disease in adult haematology patients: Trough serum concentrations in relation to outcome.

    PubMed

    Ceesay, M Mansour; Couchman, Lewis; Smith, Melvyn; Wade, Jim; Flanagan, Robert J; Pagliuca, Antonio

    2016-10-01

    Triazole antifungal drugs are widely used for the prophylaxis and treatment of invasive fungal disease (IFD). Efficacy may depend on attaining minimum effective plasma concentrations. The aim of this study was to ascertain the proportion of samples in which the recommended concentrations were achieved in patients given these drugs in relation to outcome. In-patients prescribed standard doses of fluconazole, itraconazole solution, posaconazole suspension, or oral voriconazole for at least one week were studied. Pre-dose serum triazole concentrations were measured using validated methods. There were 359 samples from 90 patients. The median (range) number of samples per patient was 3 (1-13), and the median (range) fluconazole, itraconazole, posaconazole (prophylaxis), posaconazole (treatment), and voriconazole serum concentrations were 5.64 (0.11-18), 0.57 (0-5.3), 0.31 (0.02-2.5), 0.65 (0.02-2.5), and 0.95 (0.10-5.4) mg/l, respectively. The number of samples in which the recommended pre-dose concentrations were achieved was 98 (54%), 9 (20%), 2 (18%), and 29 (49%) for itraconazole, posaconazole (>0.7 mg/l prophylaxis), posaconazole (treatment), and voriconazole, respectively. No significant differences were detected in the median triazole trough concentrations between patients with proven/probable IFD compared to those with no evidence of IFD. However, itraconazole was not detected in 10 samples (7 patients). The small number of patients who achieved the recommended trough posaconazole concentrations may explain the high rate of break-through IFD observed in patients prescribed this drug. Except for fluconazole, the number of patients prescribed standard doses of triazoles who achieved recommended trough triazole concentrations was low. The prospective use of serum triazole measurements assay may have improved outcomes with itraconazole, posaconazole, and with voriconazole.

  2. Burden and treatment patterns of invasive fungal infections in hospitalized patients in the Middle East: real-world data from Saudi Arabia and Lebanon

    PubMed Central

    Alothman, Adel F; Althaqafi, Abdulhakeem O; Matar, Madonna J; Moghnieh, Rima; Alenazi, Thamer H; Farahat, Fayssal M; Corman, Shelby; Solem, Caitlyn T; Raghubir, Nirvana; Macahilig, Cynthia; Charbonneau, Claudie; Stephens, Jennifer M

    2017-01-01

    Objectives The objective of this study was to document the burden and treatment patterns associated with invasive fungal infections (IFIs) due to Candida and Aspergillus species in Saudi Arabia and Lebanon. Methods A retrospective chart review study was conducted using data recorded from 2011 to 2012 from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of IFI due to Candida or Aspergillus, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Descriptive results were reported. Results Five hospitals participated and provided data on 102 patients with IFI (51 from Lebanon and 51 from Saudi Arabia). The mean age of the patients was 55 years, and 55% were males. Comorbidities included diabetes (41%), coronary artery disease (24%), leukemia (19%), moderate-to-severe renal disease (16%), congestive heart failure (15%), and chronic obstructive pulmonary disease (15%). Twenty percent of patients received corticosteroids prior to admission and 26% had received chemotherapy in the past 90 days. Inpatient mortality was 42%, and the mean hospital length of stay was 32.4±28.6 days. Fifty-five percent of patients required intensive care unit admission (17.2±14.1 days), 37% required mechanical ventilation (13.7±13.2 days), and 11% required dialysis (14.6±14.2 days). The most commonly used first-line antifungal was fluconazole. Conclusion Patients with IFI in Saudi Arabia and Lebanon frequently have multiple medical comorbidities and may not have traditionally observed IFI risk factors. Efforts to increase use of rapid diagnostic tests and appropriate antifungal treatments may impact the substantial mortality and high length of stay observed in these patients. PMID:28203095

  3. Fusicoccin A, a Phytotoxic Carbotricyclic Diterpene Glucoside of Fungal Origin, Reduces Proliferation and Invasion of Glioblastoma Cells by Targeting Multiple Tyrosine Kinases1

    PubMed Central

    Bury, Marina; Andolfi, Anna; Rogister, Bernard; Cimmino, Alessio; Mégalizzi, Véronique; Mathieu, Véronique; Feron, Olivier; Evidente, Antonio; Kiss, Robert

    2013-01-01

    Glioblastoma multiforme (GBM) is a deadly cancer that possesses an intrinsic resistance to pro-apoptotic insults, such as conventional chemotherapy and radiotherapy, and diffusely invades the brain parenchyma, which renders it elusive to total surgical resection. We found that fusicoccin A, a fungal metabolite from Fusicoccum amygdali, decreased the proliferation and migration of human GBM cell lines in vitro, including several cell lines that exhibit varying degrees of resistance to pro-apoptotic stimuli. The data demonstrate that fusicoccin A inhibits GBM cell proliferation by decreasing growth rates and increasing the duration of cell division and also decreases two-dimensional (measured by quantitative video microscopy) and three-dimensional (measured by Boyden chamber assays) migration. These effects of fusicoccin A treatment translated into structural changes in actin cytoskeletal organization and a loss of GBM cell adhesion. Therefore, fusicoccin A exerts cytostatic effects but low cytotoxic effects (as demonstrated by flow cytometry). These cytostatic effects can partly be explained by the fact that fusicoccin inhibits the activities of a dozen kinases, including focal adhesion kinase (FAK), that have been implicated in cell proliferation and migration. Overexpression of FAK, a nonreceptor protein tyrosine kinase, directly correlates with the invasive phenotype of aggressive human gliomas because FAK promotes cell proliferation and migration. Fusicoccin A led to the down-regulation of FAK tyrosine phosphorylation, which occurred in both normoxic and hypoxic GBM cell culture conditions. In conclusion, the current study identifies a novel compound that could be used as a chemical template for generating cytostatic compounds designed to combat GBM. PMID:23544164

  4. Fusicoccin a, a phytotoxic carbotricyclic diterpene glucoside of fungal origin, reduces proliferation and invasion of glioblastoma cells by targeting multiple tyrosine kinases.

    PubMed

    Bury, Marina; Andolfi, Anna; Rogister, Bernard; Cimmino, Alessio; Mégalizzi, Véronique; Mathieu, Véronique; Feron, Olivier; Evidente, Antonio; Kiss, Robert

    2013-04-01

    Glioblastoma multiforme (GBM) is a deadly cancer that possesses an intrinsic resistance to pro-apoptotic insults, such as conventional chemotherapy and radiotherapy, and diffusely invades the brain parenchyma, which renders it elusive to total surgical resection. We found that fusicoccin A, a fungal metabolite from Fusicoccum amygdali, decreased the proliferation and migration of human GBM cell lines in vitro, including several cell lines that exhibit varying degrees of resistance to pro-apoptotic stimuli. The data demonstrate that fusicoccin A inhibits GBM cell proliferation by decreasing growth rates and increasing the duration of cell division and also decreases two-dimensional (measured by quantitative video microscopy) and three-dimensional (measured by Boyden chamber assays) migration. These effects of fusicoccin A treatment translated into structural changes in actin cytoskeletal organization and a loss of GBM cell adhesion. Therefore, fusicoccin A exerts cytostatic effects but low cytotoxic effects (as demonstrated by flow cytometry). These cytostatic effects can partly be explained by the fact that fusicoccin inhibits the activities of a dozen kinases, including focal adhesion kinase (FAK), that have been implicated in cell proliferation and migration. Overexpression of FAK, a nonreceptor protein tyrosine kinase, directly correlates with the invasive phenotype of aggressive human gliomas because FAK promotes cell proliferation and migration. Fusicoccin A led to the down-regulation of FAK tyrosine phosphorylation, which occurred in both normoxic and hypoxic GBM cell culture conditions. In conclusion, the current study identifies a novel compound that could be used as a chemical template for generating cytostatic compounds designed to combat GBM.

  5. Immunotherapy of Fungal Infections.

    PubMed

    Datta, Kausik; Hamad, Mawieh

    2015-01-01

    Fungal organisms are ubiquitous in the environment. Pathogenic fungi, although relatively few in the whole gamut of microbial pathogens, are able to cause disease with varying degrees of severity in individuals with normal or impaired immunity. The disease state is an outcome of the fungal pathogen's interactions with the host immunity, and therefore, it stands to reason that deep/invasive fungal diseases be amenable to immunotherapy. Therefore, antifungal immunotherapy continues to be attractive as an adjunct to the currently available antifungal chemotherapy options for a number of reasons, including the fact that existing antifungal drugs, albeit largely effective, are not without limitations, and that morbidity and mortality associated with invasive mycoses are still unacceptably high. For several decades, intense basic research efforts have been directed at development of fungal immunotherapies. Nevertheless, this approach suffers from a severe bench-bedside disconnect owing to several reasons: the chemical and biological peculiarities of the fungal antigens, the complexities of host-pathogen interactions, an under-appreciation of the fungal disease landscape, the requirement of considerable financial investment to bring these therapies to clinical use, as well as practical problems associated with immunizations. In this general, non-exhaustive review, we summarize the features of ongoing research efforts directed towards devising safe and effective immunotherapeutic options for mycotic diseases, encompassing work on antifungal vaccines, adoptive cell transfers, cytokines, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), and other agents.

  6. Activity of a Long-Acting Echinocandin (CD101) and Seven Comparator Antifungal Agents Tested against a Global Collection of Contemporary Invasive Fungal Isolates in the SENTRY 2014 Antifungal Surveillance Program

    PubMed Central

    Pfaller, Michael A.; Messer, Shawn A.; Rhomberg, Paul R.

    2017-01-01

    ABSTRACT The activity of CD101 and comparator antifungal agents against 606 invasive fungal isolates collected worldwide during 2014 was evaluated using the Clinical and Laboratory Standards Institute (CLSI) method. All Candida albicans (n = 251), Candida tropicalis (n = 51), Candida krusei (n = 16), and Candida dubliniensis (n = 11) isolates were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or showed wild-type susceptibility to the other echinocandins tested. Five C. glabrata isolates (n = 100) displayed CD101 MIC values of 1 to 4 μg/ml, had elevated MICs of caspofungin (2 to >8 μg/ml), anidulafungin (2 to 4 μg/ml), and micafungin (2 to 4 μg/ml), and carried mutations on fks1 and fks2. Candida parapsilosis (n = 92) and Candida orthopsilosis (n = 10) displayed higher CD101 MIC values (ranges, 0.5 to 4 μg/ml and 0.12 to 2 μg/ml, respectively), and similar results were observed for the other echinocandins tested. Fluconazole resistance was noted among 11.0% of Candida glabrata isolates, 4.3% of C. parapsilosis isolates, and 2.0% of C. albicans and C. tropicalis isolates. The activity of CD101 against Aspergillus fumigatus (n = 56) was similar to that of micafungin and 2-fold greater than that of caspofungin but less than that of anidulafungin. These isolates had wild-type susceptibility to itraconazole, voriconazole, and posaconazole. The echinocandins had limited activity against Cryptococcus neoformans (n = 19). CD101 was as active as the other echinocandins against common fungal organisms recovered from patients with invasive fungal infections. The long half-life profile is very desirable for the prevention and treatment of serious fungal infections, especially in patients who can then be discharged from the hospital to complete antifungal therapy on an outpatient basis. PMID:28052853

  7. Nosocomial Fungal Infections: Epidemiology, Infection Control, and Prevention.

    PubMed

    Suleyman, Geehan; Alangaden, George J

    2016-12-01

    Invasive fungal infections are an important cause of morbidity and mortality in hospitalized patients and in the immunocompromised population. This article reviews the current epidemiology of nosocomial fungal infections in adult patients, with an emphasis on invasive candidiasis and aspergillosis. Recently published recommendations and guidelines for the control and prevention of these nosocomial fungal infections are summarized in this article.

  8. Clinical Utility of Fungal Screening Assays in Adults with Severe Burns

    DTIC Science & Technology

    2013-01-01

    available test, FungitellTM Glucan Assay for (1,3) b D glucan (BG) in serum (Associates of Cape Cod Inc., East Falmouth, MA), is a qualitative...considered a positive test in the United States and was used as a positive value in this study. A positive test is reported with a b D glucan concentration... Glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous

  9. One-year clinical outcomes in invasive treatment strategies for acute ST-elevation myocardial infarction complicated by cardiogenic shock in elderly patients

    PubMed Central

    Yoo, Yeon Pyo; Kang, Ki-Woon; Yoon, Hyeon Soo; Myung, Jin Cheol; Choi, Yu Jeong; Kim, Won Ho; Park, Sang Hyun; Jung, Kyung Tae; Jeong, Myung Ho

    2013-01-01

    Objective To investigate the clinical outcomes of an invasive strategy for elderly (aged ≥ 75 years) patients with acute ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). Methods Data on 366 of 409 elderly CS patients from a total of 6,132 acute STEMI cases enrolled in the Korea Acute Myocardial Infarction Registry between January 2008 and June 2011, were collected and analyzed. In-hospital deaths and the 1-month and 1-year survival rates free from major adverse cardiac events (MACE; defined as all cause death, myocardial infarction, and target vessel revascularization) were reported for the patients who had undergone invasive (n = 310) and conservative (n = 56) treatment strategies. Results The baseline clinical characteristics were not significantly different between the two groups. There were fewer in-hospital deaths in the invasive treatment strategy group (23.5% vs. 46.4%, P < 0.001). In addition, the 1-year MACE-free survival rate after invasive treatment was significantly lower compared with the conservative treatment (51% vs. 66%, P = 0.001). Conclusions In elderly patients with acute STEMI complicated by CS, the outcomes of invasive strategy are similar to those in younger patients at the 1-year follow-up. PMID:24133510

  10. Acute invasive pulmonary aspergillosis, shortly after occupational exposure to polluted muddy water, in a previously healthy subject

    PubMed Central

    Pilaniya, Vikas; Gera, Kamal; Gothi, Rajesh; Shah, Ashok

    2015-01-01

    Invasive pulmonary aspergillosis (IPA) predominantly occurs in severely neutropenic immunocompromised subjects. The occurrence of acute IPA after brief but massive exposure to Aspergillus conidia in previously healthy subjects has been documented, although only six such cases have been reported. The diagnosis was delayed in all six of the affected patients, five of whom died. We report the case of a 50-year-old HIV-negative male, a water pipeline maintenance worker, who presented with acute-onset dyspnea and fever one day after working for 2 h in a deep pit containing polluted, muddy water. Over a one-month period, his general condition deteriorated markedly, despite antibiotic therapy. Imaging showed bilateral diffuse nodules with cavitation, some of which were surrounded by ground-glass opacity suggestive of a halo sign (a hallmark of IPA). Cultures (of sputum/bronchial aspirate samples) and serology were positive for Aspergillus fumigatus. After being started on itraconazole, the patient improved. We conclude that massive exposure to Aspergillus conidia can lead to acute IPA in immunocompetent subjects. PMID:26578140

  11. A new horizon for the use of non-invasive ventilation in patients with acute respiratory distress syndrome

    PubMed Central

    2016-01-01

    Non-invasive ventilation (NIV) has assumed an important role in the management of acute respiratory failure (ARF). NIV, compared with standard medical therapy, improves survival and reduces complications in selected patients with ARF. NIV represents the first-line intervention for some forms of ARF, such as chronic obstructive pulmonary disease (COPD) exacerbations and acute cardiogenic pulmonary edema. The use of NIV is also well supported for immunocompromised patients who are at high risk for infectious complications from endotracheal intubation. Selection of appropriate patients is crucial for optimizing NIV success rates. Appropriate ventilator settings, a well-fitting and comfortable interface, and a team skilled and experienced in managing NIV are key components to its success. In a recent issue of the Journal of the American Medical Association, Patel et al. reported the results of their single-center trial of 83 patients with acute respiratory distress syndrome (ARDS) who were randomly assigned to NIV delivered via a helmet or face mask. Patients assigned to the helmet group exhibited a significantly lower intubation rate and were more likely to survive through 90 days. This perspective reviews the findings of this trial in the context of current clinical practice and in light of data from the literature focused on the potential reasons for success of NIV delivered through a helmet compared to face mask. The implications for early management of patients with ARDS are likewise discussed. PMID:27761452

  12. Primary immunodeficiencies underlying fungal infections

    PubMed Central

    Lanternier, Fanny; Cypowyj, Sophie; Picard, Capucine; Bustamante, Jacinta; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne

    2014-01-01

    Purpose of review We review the primary immunodeficiencies underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. Recent findings An increasing number of primary immunodeficiencies are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of IFN-γ immunity underlie endemic mycoses. Inborn errors of IL-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis, whereas inborn errors of CARD9 immunity underlie deep dermatophytosis and invasive candidiasis. Summary Chronic mucocutaneous candidiasis, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by primary immunodeficiencies. Each type of infection is highly suggestive of a specific type of primary immunodeficiency. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases. PMID:24240293

  13. A potential method for non-invasive acute myocardial infarction detection based on saliva Raman spectroscopy and multivariate analysis

    NASA Astrophysics Data System (ADS)

    Cao, Gang; Chen, Maowen; Chen, Yuanxiang; Huang, Zufang; Lin, Jinyong; Lin, Jia; Xu, Zhihong; Wu, Shanshan; Huang, Wei; Weng, Guoxing; Chen, Guannan

    2015-12-01

    Raman spectroscopy (RS) was employed for human saliva biochemical analysis with the aim to develop a rapidly non-invasive test for acute myocardial infarction (AMI) detection. High-quality Raman spectra were obtained from human saliva samples of 46 AMI patients and 43 healthy controls. Significant differences in Raman intensities of prominent bands were observed between AMI and normal saliva. The tentative assignment of the observed Raman bands indicated constituent and conformational differences between the two groups. Furthermore, principal component analysis (PCA) combined with linear discriminant analysis (LDA) was employed to analyze and classify the Raman spectra acquired from AMI and healthy saliva, yielding a diagnostic sensitivity of 80.4% and specificity of 81.4%. The results from this exploratory study demonstrated the feasibility and potential for developing RS analysis of human saliva into a clinical tool for rapid AMI detection and screening.

  14. Fungal melanonychia.

    PubMed

    Finch, Justin; Arenas, Roberto; Baran, Robert

    2012-05-01

    Fungal melanonychia is a relatively rare nail disorder caused by nail infection that produces brown-to-black pigmentation of the nail unit. The number of organisms implicated as etiologic agents of fungal melanonychia is increasing, and the list currently tops 21 species of dematiaceous fungi and at least 8 species of nondematiaceous fungi. These superficial infections may clinically mimic subungual melanoma and are often not responsive to traditional antifungal therapy. This article reviews the literature on fungal melanonychia and the role of fungal melanin in infection.

  15. Fungal endocarditis: current challenges.

    PubMed

    Tattevin, Pierre; Revest, Matthieu; Lefort, Agnès; Michelet, Christian; Lortholary, Olivier

    2014-10-01

    Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.

  16. Non-invasive ventilation for children with acute respiratory failure in the developing world: literature review and an implementation example.

    PubMed

    Balfour-Lynn, R E; Marsh, G; Gorayi, D; Elahi, E; LaRovere, J

    2014-06-01

    Over 2 million children die of acute respiratory infection every year, with around 98% of these deaths occurring in developing countries. Depending upon the clinical status of the patient, supplemental oxygen is usually the first line therapy. However this often proves inadequate for acute respiratory failure (ARF), in which case intubation and mechanical positive pressure ventilation are required. Adult intensive care successfully introduced non-invasive positive pressure ventilation (NIPPV) to treat ARF over a decade ago. This experience, coupled with the use of NIPPV in children with chronic respiratory insufficiency, has led to increasing use of NIPPV to treat ARF in paediatric populations. NIPPV can have similar or improved outcomes to IPPV, but with fewer complications. However there are no controlled trials of its use in children, and most data come from observational studies and retrospective reviews. In a developing world setting, where mortality from ARF is high and the risks of intubation are great and often not feasible, NIPPV can be a simple and cost-effective way to treat these patients. Its implementation in rural Northern Ghana shows NIPPV for ARF can be delivered safely with minimal training, and appears to impact significantly on mortality in those under 5 years.

  17. Non-invasive Positive Pressure Ventilation during Sleep at 3800m: relationship to Acute Mountain Sickness and sleeping oxyhemoglobin saturation

    PubMed Central

    Johnson, PL; Popa, DA; Prisk, GK; Sullivan, CE; Edwards, N

    2014-01-01

    Background and objectives Ascent to high altitude results in hypobaric hypoxia and some individuals will develop Acute Mountain Sickness, which has been shown to be associated with low oxyhemoglobin saturation during sleep. Previous research has shown that positive end-expiratory pressure by use of expiratory valves in a face mask while awake, results in a reduction in AMS symptoms and higher oxyhemoglobin saturation. We aimed to test whether pressure ventilation during sleep would prevent AMS by keeping oxyhaemoglobin higher during sleep. Methods We compared sleeping oxyhemoglobin saturation and the incidence and severity of Acute Mountain Sickness in seven subjects sleeping for two consecutive nights at 3800m above sea level using either non-invasive positive pressure ventilation that delivered positive inspiratory and expiratory airway pressure via a face mask, or sleeping without assisted ventilation. The presence and severity of Acute Mountain Sickness was assessed by administration of the Lake Louise questionnaire. Results We found significant increases in the mean and minimum sleeping oxyhemoglobin saturation and decreases in AMS symptoms in subjects who used positive pressure ventilation during sleep. Mean and minimum sleeping SaO2 was lower in subjects who developed AMS after the night spent without positive pressure ventilation. Conclusion The use of positive pressure ventilation during sleep at 3800m significantly increased the sleeping oxygen saturation; we suggest that the marked reduction in symptoms of AMS is due to this higher sleeping SaO2. We agree with the findings from previous studies that the development of AMS is associated with a lower sleeping oxygen saturation. PMID:20051046

  18. Acute toxicity, uptake and accumulation kinetics of nickel in an invasive copepod species: Pseudodiaptomus marinus.

    PubMed

    Tlili, Sofiène; Ovaert, Julien; Souissi, Anissa; Ouddane, Baghdad; Souissi, Sami

    2016-02-01

    Pseudodiaptomus marinus is a marine calanoid copepod originating of the Indo-Pacific region, who has successfully colonized new areas and it was recently observed in the European side of the Mediterranean Sea as well as in the North Sea. Actually, many questions were posed about the invasive capacity of this copepod in several non-native ecosystems. In this context, the main aim of this study was to investigate the tolerance and the bioaccumulation of metallic stress in the invasive copepod P. marinus successfully maintained in mass culture at laboratory conditions since 2 years. In order to study the metallic tolerance levels of P. marinus, an emergent trace metal, the nickel, was chosen. First, lethal concentrations determination experiments were done for 24, 48, 72 and 96 h in order to calculated LC50% but also to select a relevant ecological value for the suite of experiments. Then, three types of experiments, using a single concentration of nickel (correspond the 1/3 of 96 h-LC50%) was carried in order to study the toxico-kinetics of nickel in P. marinus. Concerning lethal concentrations, we observed that P. marinus was in the same range of sensitivity compared to other calanoid copepods exposed to nickel in the same standardized experimental conditions. Results showed that the uptake of nickel in P. marinus depends from the pathways of entrance (water of food), but also that Isochrysis galbana, used as a food source, has an important bioaccumulation capacity and a rapid uptake of nickel.

  19. Can non-invasive positive pressure ventilation prevent endotracheal intubation in acute lung injury/acute respiratory distress syndrome? A meta-analysis.

    PubMed

    Luo, Jian; Wang, Mao-yun; Zhu, Hui; Liang, Bin-miao; Liu, Dan; Peng, Xia-ying; Wang, Rong-chun; Li, Chun-tao; He, Chen-yun; Liang, Zong-an

    2014-11-01

    The role of non-invasive positive pressure ventilation (NIPPV) in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is controversial. The aim of this study was to investigate whether NIPPV could prevent endotracheal intubation and decrease mortality rate in patients with ALI/ARDS. Randomized controlled trials (RCT) which reported endotracheal intubation and mortality rate in patients with ALI/ARDS treated by NIPPV were identified in Pubmed, Medline, Embase, Central Cochrane Controlled Trials Register, Chinese National Knowledge Infrastructure, reference lists and by manual searches. Fixed- and random-effects models were used to calculate pooled relative risks. This meta-analysis included six RCT involving 227 patients. The results showed that endotracheal intubation rate was lower in NIPPV (95% confidence interval (CI): 0.44-0.80, z = 3.44, P = 0.0006), but no significant difference was found either in intensive care unit (ICU) mortality (95% CI: 0.45-1.07, z = 1.65, P = 0.10) or in hospital mortality (95% CI: 0.17-1.58, z = 1.16, P = 0.25). Only two studies discussed the aetiology of ALI/ARDS as pulmonary or extra-pulmonary, and neither showed statistical heterogeneity (I(2)  = 0%, χ(2)  = 0.31, P = 0.58), nor a significant difference in endotracheal intubation rate (95% CI: 0.35-9.08, z = 0.69, P = 0.49). In conclusion, the early use of NIPPV can decrease the endotracheal intubation rate in patients with ALI/ARDS, but does not change the mortality of these patients.

  20. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.

    PubMed

    Groll, Andreas H; Castagnola, Elio; Cesaro, Simone; Dalle, Jean-Hugues; Engelhard, Dan; Hope, William; Roilides, Emmanuel; Styczynski, Jan; Warris, Adilia; Lehrnbecher, Thomas

    2014-07-01

    Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.

  1. Serious fungal infections in Pakistan.

    PubMed

    Jabeen, K; Farooqi, J; Mirza, S; Denning, D; Zafar, A

    2017-02-04

    The true burden of fungal infection in Pakistan is unknown. High-risk populations for fungal infections [tuberculosis (TB), diabetes, chronic respiratory diseases, asthma, cancer, transplant and human immunodeficiency virus (HIV) infection] are numerous. Here, we estimate the burden of fungal infections to highlight their public health significance. Whole and at-risk population estimates were obtained from the WHO (TB), BREATHE study (COPD), UNAIDS (HIV), GLOBOCAN (cancer) and Heartfile (diabetes). Published data from Pakistan reporting fungal infections rates in general and specific populations were reviewed and used when applicable. Estimates were made for the whole population or specific populations at risk, as previously described in the LIFE methodology. Of the 184,500,000 people in Pakistan, an estimated 3,280,549 (1.78%) are affected by a serious fungal infection, omitting all cutaneous infection, oral candidiasis and allergic fungal sinusitis, which we could not estimate. Compared with other countries, the rates of candidaemia (21/100,000) and mucormycosis (14/100,000) are estimated to be very high, and are based on data from India. Chronic pulmonary aspergillosis rates are estimated to be high (39/100,000) because of the high TB burden. Invasive aspergillosis was estimated to be around 5.9/100,000. Fungal keratitis is also problematic in Pakistan, with an estimated rate of 44/100,000. Pakistan probably has a high rate of certain life- or sight-threatening fungal infections.

  2. Serious fungal diseases in the Republic of Uzbekistan.

    PubMed

    Tilavberdiev, S A; Denning, D W; Klimko, N N

    2017-03-14

    We have undertaken the first and preliminary estimation of severe and chronic mycotic diseases in the Republic of Uzbekistan, using a model proposed by LIFE (Leading International Fungal Education). Calculation was carried out based on data from 2014. Published results describing mycoses in Uzbekistan were identified. In the absence of published or official data, information about the frequency of mycoses from scientific literature elsewhere in groups at risk of development of fungal infections were taken into account. We also utilized methodology used in analogous estimations of mycoses in the Russian Federation. We estimate that of the 30.8 million population, 536,978 people (1.8% of the population) were affected by severe and chronic mycotic diseases. In 2014, there were 12,351 cases of acute invasive fungal diseases and 524,627 cases of chronic fungal diseases, including 1,941 cases of chronic pulmonary aspergillosis. The most frequent problems were recurrent vulvovaginal candidiasis (513,600 cases), trichophytosis of the scalp (6,414), and relapsed oral candidiasis (4,950). Results of the investigation indicate a significant prevalence of mycoses in the Republic of Uzbekistan.

  3. Organ Transplant Patients and Fungal Infections

    MedlinePlus

    ... of healthcare-associated infections for more information. Fungal infections can happen any time after your surgery. Fungal infections can happen ... Neofytos D, Fishman JA, Horn D, et al. Epidemiology and outcome of invasive ... in solid organ transplant recipients. Transplant Infectious Disease ...

  4. Fungal hemolysins

    PubMed Central

    Nayak, Ajay P.; Green, Brett J.; Beezhold, Donald H.

    2015-01-01

    Hemolysins are a class of proteins defined by their ability to lyse red cells but have been described to exhibit pleiotropic functions. These proteins have been extensively studied in bacteria and more recently in fungi. Within the last decade, a number of studies have characterized fungal hemolysins and revealed a fascinating yet diverse group of proteins. The purpose of this review is to provide a synopsis of the known fungal hemolysins with an emphasis on those belonging to the aegerolysin protein family. New insight and perspective into fungal hemolysins in biotechnology and health are additionally presented. PMID:22769586

  5. Predictive value of daily living score in acute respiratory failure of COPD patients requiring invasive mechanical ventilation pilot study

    PubMed Central

    2012-01-01

    Background Mechanical ventilation (MV) is imperative in many forms of acute respiratory failure (ARF) in COPD patients. Previous studies have shown the difficulty to identify parameters predicting the outcome of COPD patients treated by invasive MV. Our hypothesis was that a non specialized score as the activities daily living (ADL) score may help to predict the outcome of these patients. Methods We studied the outcome of 25 COPD patients admitted to the intensive care unit for ARF requiring invasive MV. The patients were divided into those weaning success (group A n = 17, 68%) or failure (group B n = 8, 32%). We investigated the correlation between the ADL score and the outcome and mortality. Results The ADL score was higher in group A (5.1 ±1.1 vs 3.7 ± 0.7 in group B, p < 0.01). Weaning was achieved in 76.5% of the cases with an ADL score ≥ 4 and in 23.5% of the cases with an ADL score < 4 (p < 0.05). Pulmonary function test, arterial blood gases collected during period of clinical stability and at admission and nutritional status were similar in both groups. The mortality, at six months, was 36%. The ADL score was a significant predictor of 6-month mortality (80 with an ADL score <4, 20 with an ADL score ≥4, p < 0.01). Conclusion Our pilot study demonstrates that the ADL score is predictive of weaning success and mortality at 6 months, suggesting that the assessment of daily activities should be an important component of ARF management in COPD patients. PMID:23078114

  6. Invasive coronary angiography in patients with acute exacerbated COPD and elevated plasma troponin

    PubMed Central

    Pizarro, Carmen; Herweg-Steffens, Neele; Buchenroth, Martin; Schulte, Wolfgang; Schaefer, Christian; Hammerstingl, Christoph; Werner, Nikos; Nickenig, Georg; Skowasch, Dirk

    2016-01-01

    Background In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality. Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin. Patients and methods A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included. All patients underwent coronary angiography within 72 hours after hospitalization. Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed. Results Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention. Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history. Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, P=0.01) and a significantly more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01). Neither additional laboratory parameters for inflammation and myocardial injury nor lung functional measurements differed significantly between the groups. Conclusion Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin. In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value. PMID:27695304

  7. Serious fungal infections in Canada.

    PubMed

    Dufresne, S F; Cole, D C; Denning, D W; Sheppard, D C

    2017-02-04

    There are currently no nationwide epidemiological data on fungal infections in Canada. We estimated the burden of serious fungal diseases using literature review and modeling, as per a methodology previously described by the LIFE program ( http://www.LIFE-worldwide.org ). Among the population of Canada (35.5 million in 2014), it was estimated that approximately 1.8% are affected by a serious fungal infection. Recurrent vulvovaginal candidiasis, severe asthma with fungal sensitization, and allergic bronchopulmonary aspergillosis are the most frequent infections, with population prevalences of 498,688 (1403/100,000), 73,344 (206/100,000), and 61,854 (174/100,000) cases, respectively. Over 3000 invasive fungal infections are estimated to occur annually, with incidences of 2068 cases (5.8/100,000) of invasive candidiasis, 566 cases (1.6/100,000) of invasive aspergillosis, 252 cases (0.71/100,000) of Pneumocystis pneumonia, 99 cases (0.28/100,000) of endemic mycoses, and 63 cases (0.18/100,000) of cryptococcosis. These estimates warrant validation through more formal epidemiological studies in Canada.

  8. Opportunistic invasive fungal pathogen Macrophomina phaseolina prognosis from immunocompromised humans to potential mitogenic RBL with an exceptional and novel antitumor and cytotoxic effect.

    PubMed

    Arora, P; Dilbaghi, N; Chaudhury, A

    2012-02-01

    With the ever-increasing risk for fungal infections, one can no longer ignore fungi. It is imperative that clinical manifestations "presume fungus" with their epidemiologic and pathogenic features when evaluating a potentially infected patient. In the high-risk patient groups, fungi with intrinsic resistance to antifungal agents already exist, with a tendency to emerge as opportunistic pathogens. One of the smart pathogens is Macrophomina phaseolina, with the potential to disarm plant, animal, and human immunity. The response prophylaxis may vary from antifungal therapy and surgical measures to biochemical (Rhizoctonia bataticola lectin [RBL] with antitumor and cytotoxic nature) and gene therapeutics.

  9. Automated Non-invasive Video-Microscopy of Oyster Spat Heart Rate during Acute Temperature Change: Impact of Acclimation Temperature

    PubMed Central

    Domnik, Nicolle J.; Polymeropoulos, Elias T.; Elliott, Nicholas G.; Frappell, Peter B.; Fisher, John T.

    2016-01-01

    We developed an automated, non-invasive method to detect real-time cardiac contraction in post-larval (1.1–1.7 mm length), juvenile oysters (i.e., oyster spat) via a fiber-optic trans-illumination system. The system is housed within a temperature-controlled chamber and video microscopy imaging of the heart was coupled with video edge-detection to measure cardiac contraction, inter-beat interval, and heart rate (HR). We used the method to address the hypothesis that cool acclimation (10°C vs. 22°C—Ta10 or Ta22, respectively; each n = 8) would preserve cardiac phenotype (assessed via HR variability, HRV analysis and maintained cardiac activity) during acute temperature changes. The temperature ramp (TR) protocol comprised 2°C steps (10 min/experimental temperature, Texp) from 22°C to 10°C to 22°C. HR was related to Texp in both acclimation groups. Spat became asystolic at low temperatures, particularly Ta22 spat (Ta22: 8/8 vs. Ta10: 3/8 asystolic at Texp = 10°C). The rate of HR decrease during cooling was less in Ta10 vs. Ta22 spat when asystole was included in analysis (P = 0.026). Time-domain HRV was inversely related to temperature and elevated in Ta10 vs. Ta22 spat (P < 0.001), whereas a lack of defined peaks in spectral density precluded frequency-domain analysis. Application of the method during an acute cooling challenge revealed that cool temperature acclimation preserved active cardiac contraction in oyster spat and increased time-domain HRV responses, whereas warm acclimation enhanced asystole. These physiologic changes highlight the need for studies of mechanisms, and have translational potential for oyster aquaculture practices. PMID:27445833

  10. Automated Non-invasive Video-Microscopy of Oyster Spat Heart Rate during Acute Temperature Change: Impact of Acclimation Temperature.

    PubMed

    Domnik, Nicolle J; Polymeropoulos, Elias T; Elliott, Nicholas G; Frappell, Peter B; Fisher, John T

    2016-01-01

    We developed an automated, non-invasive method to detect real-time cardiac contraction in post-larval (1.1-1.7 mm length), juvenile oysters (i.e., oyster spat) via a fiber-optic trans-illumination system. The system is housed within a temperature-controlled chamber and video microscopy imaging of the heart was coupled with video edge-detection to measure cardiac contraction, inter-beat interval, and heart rate (HR). We used the method to address the hypothesis that cool acclimation (10°C vs. 22°C-Ta10 or Ta22, respectively; each n = 8) would preserve cardiac phenotype (assessed via HR variability, HRV analysis and maintained cardiac activity) during acute temperature changes. The temperature ramp (TR) protocol comprised 2°C steps (10 min/experimental temperature, Texp) from 22°C to 10°C to 22°C. HR was related to Texp in both acclimation groups. Spat became asystolic at low temperatures, particularly Ta22 spat (Ta22: 8/8 vs. Ta10: 3/8 asystolic at Texp = 10°C). The rate of HR decrease during cooling was less in Ta10 vs. Ta22 spat when asystole was included in analysis (P = 0.026). Time-domain HRV was inversely related to temperature and elevated in Ta10 vs. Ta22 spat (P < 0.001), whereas a lack of defined peaks in spectral density precluded frequency-domain analysis. Application of the method during an acute cooling challenge revealed that cool temperature acclimation preserved active cardiac contraction in oyster spat and increased time-domain HRV responses, whereas warm acclimation enhanced asystole. These physiologic changes highlight the need for studies of mechanisms, and have translational potential for oyster aquaculture practices.

  11. Analysis of the invasive strategy decision in patients with acute coronary syndrome without ST-segment elevation in a real-world setting.

    PubMed

    De Abreu, Maximiliano; Mariani, Javier A; Silberstein, Alejandro; Guridi, Cristian; Hecht, Gabriela; Gagliardi, Juan A; Doval, Hernán C; Tajer, Carlos D

    2014-06-15

    Observational studies have reported a marked discrepancy between the risk estimated by scores and the use of an invasive strategy in patients with acute coronary syndromes. The objective is to describe the criteria used to decide an early invasive strategy and to determine the differences between those criteria and the thrombolysis in myocardial infarction risk score (TRS). Patients entered to the Epi-Cardio registry with a diagnosis of non-ST-elevation acute coronary syndrome were analyzed. A logistic regression model including variables associated with an early invasive strategy was developed and validated in 2 consecutive cohorts. The association between the TRS and the clinical decision model with an early invasive strategy was evaluated by receiver operating characteristic (ROC) curves. We included a total of 3,187 patients. In the derivation cohort, variables associated with an early invasive strategy were previous angioplasty (odds ratio [OR] 1.63), hypercholesterolemia (OR 1.36), ST changes (OR 1.49), elevated biomarkers (OR 1.42), catheterization laboratory availability (OR 1.7), recurrent angina (OR 3.45), age (OR 0.98), previous coronary bypass (OR 0.65), previous heart failure (OR 0.40), and heart rate at admission (OR 0.98). The areas under the ROC curves to predict invasive strategy were 0.55 for the TRS and 0.69 for the clinical decision model, p <0.0001. In the validation cohort, ROC areas were 0.58 and 0.70, respectively, p <0.0001. In conclusion, invasive strategy was guided by variables not completely included in risk scores. The clinical, evolutionary, and structural variables included in the model can explain, partially, the discordance existing between risk stratification and medical strategies.

  12. Fungal Tests

    MedlinePlus

    ... diagnosis is needed, as in cases of persistent, deep, or systemic infections, more extensive testing may be ... mouth (thrush) Vaginal itching and discharge (yeast infection) Deep and systemic fungal infections may cause a variety ...

  13. Spatial and taxonomical overlap of fungi on phylloplanes and invasive alien ladybirds with fungal infections in tree crowns of urban green spaces.

    PubMed

    Howe, Andy G; Ravn, Hans Peter; Jensen, Annette B; Meyling, Nicolai V

    2016-09-01

    Occurrence of entomopathogenic fungi on phylloplanes in Tilia × europaea crowns between 1 and 13 m was assessed in urban parks. Prevalence of fungal infections in ladybirds (Coleoptera: Coccinellidae) collected from Tilia × europaea was assessed to determine whether fungi found on phylloplanes also occurred as infections in ladybirds. Isaria spp. was most abundant on phylloplanes (mean colony forming units (CFU) per leaf ± SE, 0.33 ± 0.03) followed by Beauveria spp. (0.22 ± 0.02 CFU per leaf) and Lecanicillium spp. (0.19 ± 0.02 CFU per leaf). Densities of inoculum were higher in inner crowns and decreased with height, although Lecanicillium spp. peaked at 5-7 m. Upper phylloplane surfaces harboured higher densities of Isaria spp. and Beauveria spp. than lower surfaces, whereas Lecanicillium spp. was equally distributed. Most prevalent on ladybirds were Isaria spp. (20.6% Harmonia axyridis; 4.8% natives), Lecanicillium spp. (13.6% H. axyridis; 4.8% natives), with fewer Beauveria spp. infections (2.6% H. axyridis). Molecular identification revealed Beauveria bassiana, B. pseudobassiana, Isaria farinosa and Lecanicillium muscarium among isolates of both tree and ladybird origin. Tilia × europaea phylloplanes support a diverse assemblage of entomopathogenic fungal species with a different prevalence in coccinellids compared to their relative abundance in this habitat.

  14. Fungal allergens.

    PubMed Central

    Horner, W E; Helbling, A; Salvaggio, J E; Lehrer, S B

    1995-01-01

    Airborne fungal spores occur widely and often in far greater concentrations than pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal spores induce type I hypersensitivity (allergic) respiratory reactions in sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30% of atopic (allergy-predisposed) individuals or up to 6% of the general population. Diagnosis and immunotherapy of allergy to fungi require well-characterized or standardized extracts that contain the relevant allergen(s) of the appropriate fungus. Production of standardized extracts is difficult since fungal extracts are complex mixtures and a variety of fungi are allergenic. Thus, the currently available extracts are largely nonstandardized, even uncharacterized, crude extracts. Recent significant progress in isolating and characterizing relevant fungal allergens is summarized in the present review. Particularly, some allergens from the genera Alternaria, Aspergillus, and Cladosporium are now thoroughly characterized, and allergens from several other genera, including some basidiomycetes, have also been purified. The availability of these extracts will facilitate definitive studies of fungal allergy prevalence and immunotherapy efficacy as well as enhance both the diagnosis and therapy of fungal allergy. PMID:7621398

  15. Transcutaneous Intraluminal Impedance Measurement for Minimally Invasive Monitoring of Gastric Motility: Validation in Acute Canine Models

    PubMed Central

    Poscente, Michael D.; Wang, Gang; Filip, Dobromir; Ninova, Polya; Muench, Gregory; Yadid-Pecht, Orly; Mintchev, Martin P.; Andrews, Christopher N.

    2014-01-01

    Transcutaneous intraluminal impedance measurement (TIIM) is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models. Methods. Eight mongrel dogs were randomly divided into 2 groups: half received an active TIIM pill and half received an identically sized sham capsule. After 24-hour fasting and transoral administration of the pill (active or sham), two force transducers (FT) were sutured onto the antral serosa at laparotomy. After closure, three standard cutaneous electrodes were placed on the abdomen, registering the transluminally emitted voltage. Thirty-minute baseline recordings were followed by pharmacological induction of gastric contractions using neostigmine IV and another 30-minute recording. Normalized one-minute baseline and post-neostigmine gastric motility indices (GMIs) were calculated and Pearson correlation coefficients (PCCs) between cutaneous and FT GMIs were obtained. Statistically significant GMI PCCs were seen in both baseline and post-neostigmine states. There were no significant GMI PCCs in the sham capsule test. Further chronic animal studies of this novel long-term gastric motility measurement technique are needed before testing it on humans. PMID:25574163

  16. Diastolic function in healthy humans: non-invasive assessment and the impact of acute and chronic exercise.

    PubMed

    George, Keith P; Naylor, Louise H; Whyte, Greg P; Shave, Rob E; Oxborough, David; Green, Daniel J

    2010-01-01

    Left ventricular (LV) diastolic function is important because the enhanced systolic function that underpins high levels of cardio-respiratory fitness has to be matched by changes in LV filling, and LV diastolic dysfunction plays a key early role in the development and progression of a myriad of cardiovascular diseases. This review serves to detail knowledge in relation to: (1) the definition of diastole and the mechanical processes that occur during the diastolic period, (2) the quantitative assessment of diastolic function, predominantly focusing on non-invasive echocardiographic imaging modes such as tissue Doppler imaging and deformation analysis, (3) the impact of acute aerobic exercise on diastolic function, from the augmentation of function necessary to meet the demand for an increased cardiac output at exercise onset, to current concerns related to the impact of prolonged or ultra-endurance activity on diastolic function during recovery, (4) the adaptation in diastolic function observed with chronic aerobic exercise training in athletes and sedentary individuals who undergo training programmes, and (5) directions for future research.

  17. Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

    PubMed Central

    Lee, Robert J.; Workman, Alan D.; Carey, Ryan M.; Chen, Bei; Rosen, Phillip L.; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.

    2016-01-01

    Aflatoxins are mycotoxins secreted by Aspergillus flavus, which can colonize the respiratory tract and cause fungal rhinosinusitis or bronchopulmonary aspergillosis. A. flavus is the second leading cause of invasive aspergillosis worldwide. Because many respiratory pathogens secrete toxins to impair mucociliary immunity, we examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, we imaged ciliary beat frequency (CBF), intracellular calcium, and nitric oxide (NO). Exposure to aflatoxins (0.1 to 10 μM; 5 to 10 minutes) reduced baseline (~6–12%) and agonist-stimulated CBF. Conditioned media (CM) from A. fumigatus, A. niger, and A. flavus cultures also reduced CBF by ~10% after 60 min exposure, but effects were blocked by an anti-aflatoxin antibody only with A. flavus CM. CBF reduction required protein kinase C but was not associated with changes in calcium or NO. However, AFB2 reduced NO production by ~50% during stimulation of the ciliary-localized T2R38 receptor. Using a fluorescent reporter construct expressed in A549 cells, we directly observed activation of PKC activity by AFB2. Aflatoxins secreted by respiratory A. flavus may impair motile and chemosensory functions of airway cilia, contributing to pathogenesis of fungal airway diseases. PMID:27623953

  18. Alternative complement pathway activation during invasive coronary procedures in acute myocardial infarction and stable angina pectoris.

    PubMed

    Horváth, Zsófia; Csuka, Dorottya; Vargova, Katarina; Kovács, Andrea; Leé, Sarolta; Varga, Lilian; Préda, István; Tóth Zsámboki, Emese; Prohászka, Zoltán; Kiss, Róbert Gábor

    2016-12-01

    The effect of invasive percutaneous coronary procedures on complement activation has not been elucidated. We enrolled stable angina patients with elective percutaneous coronary intervention (SA-PCI, n=24), diagnostic coronary angiography (CA, n=52) and 23 patients with ST segment elevation myocardial infarction and primary PCI (STEMI-PCI). Complement activation products (C1rC1sC1inh, C3bBbP and SC5b-9) were measured on admission, 6 and 24h after coronary procedures. The alternative pathway product, C3bBbP significantly and reversibly increased 6h after elective PCI (baseline: 7.81AU/ml, 6h: 16.09AU/ml, 24h: 4.27AU/ml, p<0.01, n=23) and diagnostic angiography (baseline: 6.13AU/ml, 6h: 12.08AU/ml, 24h: 5.4AU/ml, p<0.01, n=52). Six hour C3bBbP values correlated with post-procedural CK, creatinine level and the applied contrast material volume (r=0.41, r=0.4, r=0.3, p<0.05, respectively). In STEMI-PCI, baseline C3bBbP level was higher, compared to SA-PCI or CA patients (11.33AU/ml vs. 7.81AU/ml or 6.13AU/ml, p<0.001). Similarly, the terminal complex (SC5b-9) level was already elevated at baseline compared to SA-PCI group (3.49AU/ml vs. 1.87AU/ml, p=0.011). Complement pathway products did not increase further after primary PCI. Elective coronary procedures induced transient alternative complement pathway activation, influenced by the applied contrast volume. In STEMI, the alternative complement pathway is promptly activated during the atherothrombotic event and PCI itself had no further detectable effect.

  19. Distribution of filamentous fungi causing invasive fungal disease at the Haematological Unit, Hospital de Clínicas de Porto Alegre, Brazil.

    PubMed

    Aquino, Valério Rodrigues; Verçosa, Emanuelle Bergonsi; Falhauber, Gustavo; Lunardi, Luciano Werle; Silla, Lucia; Pasqualotto, Alessandro Comarú

    2010-01-01

    Very limited data are available in the literature to elucidate the aetiology of invasive mould infections in Latin America. Here we report that Aspergillus species caused only half of such cases in a cohort study conducted over 21 months in a university hospital in Porto Alegre, Southern Brazil. Fusarium spp. were the second most prevalent moulds (20.7%), followed by Zygomycetes (13.8%). The importance of obtaining local epidemiological data for adequately guiding empirical antifungal therapy is reinforced.

  20. Combined neuromodulatory interventions in acute experimental pain: assessment of melatonin and non-invasive brain stimulation

    PubMed Central

    da Silva, Nádia Regina Jardim; Laste, Gabriela; Deitos, Alícia; Stefani, Luciana Cadore; Cambraia-Canto, Gustavo; Torres, Iraci L. S.; Brunoni, Andre R.; Fregni, Felipe; Caumo, Wolnei

    2015-01-01

    Transcranial direct current stimulation (tDCS) and melatonin can effectively treat pain. Given their potentially complementary mechanisms of action, their combination could have a synergistic effect. Thus, we tested the hypothesis that compared to the control condition and melatonin alone, tDCS combined with melatonin would have a greater effect on pain modulatory effect, as assessed by quantitative sensory testing (QST) and by the pain level during the Conditioned Pain Modulation (CPM)-task. Furthermore, the combined treatment would have a greater cortical excitability effect as indicated by the transcranial magnetic stimulation (TMS) and on the serum BDNF level. Healthy males (n = 20), (aged 18–40 years), in a blinded, placebo-controlled, crossover, clinical trial, were randomized into three groups: sublingual melatonin (0.25 mg/kg) + a-tDCS, melatonin (0.25 mg/kg) + sham-(s)-tDCS, or sublingual placebo+sham-(s)-tDCS. Anodal stimulation (2 mA, 20 min) was applied over the primary motor cortex. There was a significant difference in the heat pain threshold (°C) for melatonin+a-tDCS vs. placebo+s-tDCS (mean difference: 4.86, 95% confidence interval [CI]: 0.9 to 8.63) and melatonin+s-tDCS vs. placebo+s-tDCS (mean: 5.16, 95% CI: 0.84 to 8.36). There was no difference between melatonin+s-tDCS and melatonin+a-tDCS (mean difference: 0.29, 95% CI: −3.72 to 4.23). The mean change from the baseline on amplitude of motor evocate potential (MEP) was significantly higher in the melatonin+a-tDCS (−19.96% ± 5.2) compared with melatonin+s-tDCS group (−1.36% ± 5.35) and with placebo+s-tDCS group (3.61% ± 10.48), respectively (p < 0.05 for both comparisons). While melatonin alone or combined with a-tDCS did not significantly affect CPM task result, and serum BDNF level. The melatonin effectively reduced pain; however, its association with a-tDCS did not present an additional modulatory effect on acute induced pain. PMID:25873871

  1. [Using non-invasive mask lung ventilation in cardiosurgical patients with acute respiratory distress syndrome].

    PubMed

    Eremenko, A A; Levikov, D I; Egorov, V M; Zorin, D E; Kolomiets, V Ia

    2004-01-01

    Twenty patients aged 33 to 71 (54 +/- 6) years (male - 13, female - 7) operated on the heart and main vessels were included in the case study. I.e. those patient were investigated, whose immediate postoperative results were complicated by the syndrome of multiple organ failure (SMOF) that developed due to different-etiology shock, huge blood loss and hemotransfusion or to the syndrome of acute postperfusion lung damage. NIMLV was made at the resolution stage of SMOF and ARDS after artificial pulmonary ventilation (APL) for as long as 5-7 days. The indications for extubation of patients were as follows: PaO2/FiO2 of 200 and more mm Hg, respiratory rate (RR) of less than 30 per min, respiratory volume of more than 6 ml/kg with pressure support at inspiration of less than 5 cm H2O and with the total pressure at the exhalation end of no more than 3 cm H2O. Mask ventilation sessions were started in a growing dyspnea of more than 26 per min, a decreased content of oxyhemoglobin in arterial blood (below 95% at oxygen inhalation of 10-15 l/min), involvement of auxiliary muscles in breathing and at subjective complaints of patients related with complicated breathing and with being short of air. The mask SIMV ventilation with a preset apparatus-aided rate of inhales of 2-6/min, with Bi-PAP and PSV inhale pressure of 15 cm/ H2O and with PEEP of 3-5 cm/ H2O was made by 40-120 min sessions; the number of IFMLV sessions ranged from 6 to 22/patient, mean - 11 +/- 1.1 h. The total IFMLV duration was 10.7 +/- 1.1 h. The need for respiratory support persisted for 4-6 days after extubation. In 18 (90%) of 20 patients, the mask pulmonary ventilation resolved the respiratory insufficiency. Two (10%) patients were reintubated because of progressing multiorgan failure and because of obturation of the left main bronchus. A questioning of patients on the comfort degree of mask ventilation denoted the Flow-by triggering to be by far better tolerated by patients versus the pressure

  2. Potential Roles of Fungal Extracellular Vesicles during Infection

    PubMed Central

    Joffe, Luna S.; Nimrichter, Leonardo

    2016-01-01

    ABSTRACT Extracellular vesicles (EVs) are produced by virtually all cell types. Within the past few years, work in this field has revealed more information about fungal EVs. Fungal EVs have been shown to carry proteins, lipids, pigments, polysaccharides, and RNA; these components are known virulence factors, a fact which supports the hypothesis that fungal EVs concentrate pathogenic determinants. Additionally, recent studies have demonstrated that fungal EVs stimulate the host immune system. In this review, putative roles of fungal EVs are discussed, including their potential as vaccination tools and their possible contribution to pathogenesis in invasive fungal diseases. PMID:27390779

  3. Serious fungal infections in Portugal.

    PubMed

    Sabino, R; Verissímo, C; Brandão, J; Martins, C; Alves, D; Pais, C; Denning, D W

    2017-02-10

    There is a lack of knowledge on the epidemiology of fungal infections worldwide because there are no reporting obligations. The aim of this study was to estimate the burden of fungal disease in Portugal as part of a global fungal burden project. Most published epidemiology papers reporting fungal infection rates from Portugal were identified. Where no data existed, specific populations at risk and fungal infection frequencies in those populations were used in order to estimate national incidence or prevalence, depending on the condition. An estimated 1,510,391 persons develop a skin or nail fungal infection each year. The second most common fungal infection in Portugal is recurrent vulvovaginal candidiasis, with an estimated 150,700 women (15-50 years of age) suffering from it every year. In human immunodeficiency virus (HIV)-infected people, oral or oesophageal candidiasis rates were estimated to be 19.5 and 16.8/100,000, respectively. Candidaemia affects 2.19/100,000 patients, in a total of 231 cases nationally. Invasive aspergillosis is less common than in other countries as chronic obstructive pulmonary disease (COPD) is uncommon in Portugal, a total of 240 cases annually. The estimated prevalence of chronic pulmonary aspergillosis after tuberculosis (TB) is 194 cases, whereas its prevalence for all underlying pulmonary conditions was 776 patients. Asthma is common (10% in adults) and we estimate 16,614 and 12,600 people with severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis, respectively. Sixty-five patients develop Pneumocystis pneumonia in acquired immune deficiency syndrome (AIDS) and 13 develop cryptococcosis. Overall, we estimate a total number of 1,695,514 fungal infections starting each year in Portugal.

  4. Prognostic Significance of NT-proBNP Levels in Patients over 65 Presenting Acute Myocardial Infarction Treated Invasively or Conservatively

    PubMed Central

    Drewniak, Wojciech; Szybka, Wojciech; Bielecki, Dariusz; Malinowski, Michal; Kotlarska, Joanna; Krol-Jaskulska, Agnieszka; Popielarz-Grygalewicz, Agata; Konwicka, Aleksandra; Dąbrowski, Marek

    2015-01-01

    Objectives. Assessment of prognostic significance of NT-proBNP level and the effects of invasive (I) and conservative (C) treatment of acute myocardial infarction (AMI) in patients over 65. Materials and Methods. One-year survival was assessed in 286 consecutive patients with AMI aged 65–100 (79 ± 8) subjected to I or C treatment (136 and 150 individuals), respectively. Results. 245 (85%) patients survived in-hospital stay: 124 (91.1%) received I treatment and 121 (80.6%) received C treatment. Heart failure (HF) was diagnosed in 30 patients receiving I treatment (22.6%) and in 71 subjected to C treatment (47.3%), p < 0,0001. NT-proBNP levels in the latter group were significantly higher than in the 185 patients without HF (12311 ± 13560 pg/mL versus 4773 ± 8807 pg/mL, p < 0.0001). NT-proBNP levels after coronary angioplasty were lower than in patients receiving C treatment (5922 ± 10250 pg/mL versus 8718 ± 12024 pg/mL, p = 0.0002). Left ventricular ejection fraction was significantly higher in I patients than in C patients (47 ± 13% versus 42 ± 11.6%, p = 0.004). During the one-year follow-up, 82.3% of I patients and 61.2% of the C patients survived (p < 0.0003). There was a significantly lower probability of death at NT-proBNP below 8548.5 pg/mL. Conclusions. The NT-proBNP level in the first day of AMI is a good prognosticator. One-year follow-up prognosis for patients who received I treatment in the AMI is better than that for C patients. I patients exhibit superior left ventricular function after angioplasty and in the follow-up. PMID:26539524

  5. Salvage combination antifungal therapy for acute invasive aspergillosis may improve outcomes: a systematic review and meta-analysis

    PubMed Central

    Panackal, Anil A.; Parisini, Emilio; Proschan, Michael

    2014-01-01

    Summary Objective A meta-analysis was performed to compare mold-active triazoles or lipid amphotericin B plus an echinocandin to non-echinocandin monotherapy for acute invasive aspergillosis (IA). Methods We searched PubMed, EMBASE, and other databases through May 2013 unrestricted by language. We included observational and experimental studies wherein patients with proven or probable IA by EORTC/MSG criteria underwent our comparative intervention. PRISMA and MOOSE guidelines were followed and quality was assessed using the Jadad and Newcastle–Ottawa criteria. Meta-regression with fixed and random effects and sensitivity analyses were performed. The primary study outcome measure was 12-week overall mortality. The secondary outcome assessed was complete and partial response. Results Only observational studies of primary 12-week survival showed heterogeneity (I2 = 48.96%, p = 0.05). For salvage IA therapy, fixed effects models demonstrated improved 12-week survival (Peto odds ratio (OR) 1.80, 95% confidence interval (CI) 1.08–3.01) and success (Peto OR 2.17, 95% CI 1.21–3.91) of combination therapy. Significance remained after applying random effects as a sensitivity analysis (12-week survival: Peto OR 1.90, 95% CI 1.04–3.46, and unchanged value for success). Restriction to high quality studies and including echinocandins as the comparator for refractory IA revealed an adjusted OR of 1.72 (95% CI 0.96–3.09; p = 0.07) for global success, while the survival endpoint remained unaltered. Conclusions Combination antifungals for IA demonstrate improved outcomes over monotherapy in the salvage setting. Clinicians should consider this approach in certain situations. PMID:25240416

  6. Efficacy of Intralipid infusion in reducing amphotericin-B-associated nephrotoxicity in head and neck invasive fungal infection: A randomized, controlled trial.

    PubMed

    Hasibi, Mehrdad; Jafari, Sirous; Manshadi, Seyyed Ali; Asadollahi, Marjan; Salehi, Mohammadreza; Zarch, Varasteh Vakili; Kouhi, Ali

    2017-02-01

    Amphotericin B deoxycholate (ABD) is the best therapeutic agent available for the treatment of most systemic fungal infections. However, some untoward adverse effects such as nephrotoxicity may limit its appropriate therapeutic use. We conducted a randomized, controlled trial ofthe infusion of fat emulsion (Intralipid) shortly after the infusion of ABD to evaluate its effects on reducing ABD-associated nephrotoxicity. Our patient population was made up of 31 patients who were randomized into two groups: an intervention group (n = 16) and a control group (15 patients). There were no statistically significant differences between the two groups in demographic or clinical variables. All patients received 1mg/kg/day of ABD in dextrose 5%. In addition, the patients in the intervention arm received Intralipid 10%, which was started as soon as possible within 1 hour after the infusion of ABD. ABD-associated nephrotoxicity was defined as a minimum 50% increase in baseline serum creatinine to a minimum of 2mg/dl. We also measured daily serum creatinine changes during the first 2 weeks of treatment, and we compared some other relevant indices of renal function, as well as ABD-related hypokalemia. We found no statistically significant differences between the two treatments in terms of ABD-associated nephrotoxicity or any of the other indices. We conclude that the administration of Intralipid 10% early after infusion of ABD in dextrose 5% does not have any effect in decreasing ABD-associated nephrotoxicity or hypokalemia.

  7. Fungal polysaccharides.

    PubMed

    San-Blas, G; Suzuki, S; Hearn, V; Pinel, C; Kobayashi, H; Mendez, C; Niño, G; Nishikawa, A; San-Blas, F; Shibata, N

    1994-01-01

    Fungal polysaccharides are cell wall components which may act as antigens or as structural substrates. As antigens, the role of mannans in Saccharomyces cerevisiae and Candida albicans, and of glycoproteins in Aspergillus fumigatus are discussed. Analyses on beta-glucan synthetase in Paracoccidioides brasiliensis and the inhibitory effect of Hansenula mrakii killer toxin on beta-glucan biosynthesis are also considered.

  8. Fungal arthritis

    MedlinePlus

    ... A.D.A.M. Editorial team. Related MedlinePlus Health Topics Fungal Infections Infectious Arthritis Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare ... for online health information and services. Learn more about A.D. ...

  9. Fungal Infections

    MedlinePlus

    ... it, you'll be saying bye-bye to fungi (say: FUN-guy). What Is a Fungal Infection? Fungi , the word for more than one fungus, can ... but of course, they're not!). Because the fungi that cause tinea (ringworm) live on different parts ...

  10. Fungal Entomopathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal entomopathogens are important biological control agents worldwide and have been the subject of intense research for more than100 years. They exhibit both sexual and asexual reproduction and produce different types of infective propagules. Their mode of action against insects involves attachme...

  11. First Report of CD4 Lymphopenia and Defective Neutrophil Functions in a Patient with Amebiasis Associated with CMV Reactivation and Severe Bacterial and Fungal Infections

    PubMed Central

    Ghrenassia, Etienne; Guihot, Amélie; Dong, Yuan; Robinet, Pauline; Fontaine, Thierry; Lacombe, Karine; Lescot, Thomas; Meyohas, Marie-Caroline; Elbim, Carole

    2017-01-01

    We report the case of a patient with acute necrotizing colitis due to invasive amebiasis associated with CD4 lymphopenia and impaired neutrophil responses. The course of the disease was characterized by CMV reactivation and severe and recurrent bacterial and fungal infections, which might be related to the decreased CD4 T cell count and the impaired functional capacities of neutrophils, respectively. The clinical outcome was positive with normalization of both CD4 cell count and neutrophil functions. PMID:28243230

  12. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    SciTech Connect

    Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun

    2015-04-03

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

  13. Different types of fungal sinusitis occurring concurrently: implications for therapy.

    PubMed

    Rupa, V; Thomas, Meera

    2013-02-01

    The purpose of this study is to describe the clinical and histopathological features, management and outcome of a series of patients with simultaneous occurrence of invasive and non-invasive fungal sinusitis (mixed fungal sinusitis). The histopathological records of patients with fungal sinusitis seen over the last 6 years were reviewed. The clinical, histopathological, treatment and follow up details of all cases with mixed fungal sinusitis were noted. Six cases of mixed fungal sinusitis with concurrent occurrence of chronic granulomatous fungal sinusitis and allergic fungal sinusitis (AFS) were seen during the study period. Most (83.3 %) had bilateral disease. All patients had undergone prior endoscopic sinus surgery at least once within the previous 2 years. Histopathological features showed predominance of invasive disease in half the patients. Except for one patient who did not report for follow up, all patients with predominant chronic granulomatous fungal sinusitis received systemic antifungal therapy and inhaled steroids. Those with predominant features of AFS received oral and inhaled steroids. Five patients with mixed fungal sinusitis who had follow up ranging from 6 months to 5 years were disease free following treatment. Mixed fungal sinusitis should be recognized by the surgeon and pathologist as a separate category of fungal sinusitis whose treatment depends on accurate histological diagnosis. A good outcome may be expected with appropriate therapy.

  14. Treatment strategies for invasive aspergillosis in neutropenic patients: voriconazole or liposomal amphotericin-B?

    PubMed

    Pagano, L; Valentini, C G; Fianchi, L; Caira, M

    2011-02-01

    The proportion of patients with cancers who develop invasive fungal infections has increased dramatically over the past few decades. Most of these infections are diagnosed in patients with hematological malignancies, mainly in patients with acute myeloid leukemia and those undergoing allogeneic hematopoietic stem cell transplantation. For years deoxycolate amphotericin B has been considered the drug of choice for the treatment of invasive aspergillosis, but it has been outclassed by its lipid formulations and new triazoles (i.e. voriconazole), that produced better response rates; nonetheless recovery from neutropenia remains the most important factor influencing outcome.

  15. Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels.

    PubMed

    Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L; Bhatnagar, Deepak; Cleveland, Thomas E

    2014-01-01

    A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus.

  16. Fungal farming in a snail

    PubMed Central

    Silliman, Brian R.; Newell, Steven Y.

    2003-01-01

    Mutualisms between fungi and fungus-growing animals are model systems for studying coevolution and complex interactions between species. Fungal growing behavior has enabled cultivating animals to rise to major ecological importance, but evolution of farming symbioses is thought to be restricted to three terrestrial insect lineages. Surveys along 2,000 km of North America's Atlantic coast documented that the marine snail Littoraria irrorata grazes fungus-infected wounds on live marsh grass throughout its range. Field experiments demonstrate a facultative, farming mutualism between Littoraria and intertidal fungi. Snails graze live grass primarily not to feed but to prepare substrate for fungal growth and consume invasive fungi. Fungal removal experiments show that snails and fungi act synergistically to suppress marsh grass production. These results provide a case of fungus farming in the marine environment and outside the class Insecta and reveal a previously undemonstrated ecological mechanism (i.e., facilitation of fungal invasion) by which grazers can exert top-down control of marine plant production. PMID:14657360

  17. Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

    PubMed Central

    Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

    2016-01-01

    Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

  18. Fungal infections in solid organ transplantation.

    PubMed

    Silveira, Fernanda P; Husain, Shahid

    2007-06-01

    Fungal infections in solid organ transplant recipients continue to be a significant cause of morbidity and mortality. Candida spp. and Aspergillus spp. account for most invasive fungal infections. The incidence of fungal infection varies with type of solid organ transplant. Liver transplant recipients have highest reported incidence of candida infections while lung transplant recipients have highest rate of Aspergillus infections. Recent epidemiological studies suggest the emergence of resistant strains of candida as well as mycelial fungi other than Aspergillus in these patients. The current review incorporates the recent changes in the epidemiology of fungal infections in solid organ transplant recipients and highlights the newer data on the diagnosis, prophylaxis and treatment of fungal infections in these patients.

  19. Serious fungal infections in Peru.

    PubMed

    Bustamante, B; Denning, D W; Campos, P E

    2017-02-10

    Epidemiological data about mycotic diseases are limited in Peru and estimation of the fungal burden has not been previously attempted. Data were obtained from the Peruvian National Institute of Statistics and Informatics, UNAIDS and from the Ministry of Health's publications. We also searched the bibliography for Peruvian data on mycotic diseases, asthma, COPD, cancer and transplants. Incidence or prevalence for each fungal disease were estimated in specific populations at risk. The Peruvian population for 2015 was 31,151,543. In 2014, the estimated number of HIV/AIDS and pulmonary tuberculosis cases was 88,625, 38,581 of them not on ART, and 22,027, respectively. A total of 581,174 cases of fungal diseases were estimated, representing approximately 1.9% of the Peruvian population. This figure includes 498,606, 17,361 and 4,431 vulvovaginal, oral and esophageal candidiasis, respectively, 1,557 candidemia cases, 3,593 CPA, 1,621 invasive aspergillosis, 22,453 allergic bronchopulmonary aspergilllosis, 29,638 severe asthma with fungal sensitization, and 1,447 Pneumocystis pneumonia. This first attempt to assess the fungal burden in Peru needs to be refined. We believe the figure obtained is an underestimation, because of under diagnosis, non-mandatory reporting and lack of a surveillance system and of good data about the size of populations at risk.

  20. Serious fungal infections in Chile.

    PubMed

    Alvarez Duarte, E; Denning, D W

    2017-02-10

    The incidence and prevalence of fungal infections in Chile are unknown. Here, we have estimated the burden of serious fungal diseases from data obtained from clinical reports, WHO reports, Chilean census, OECD reports and comprehensive literature search available on PubMed and SciELO, among other scientific resources. Due the lack of official data about fungal diseases, frequencies were calculated based on the specific populations at risk. Recurrent vulvovaginal candidiasis (>4 episodes/year) is estimated to occur in 3108/100,000. Using a low international average rate of 5/100,000, we estimate 878 candidaemia cases and 132 patients with intra-abdominal candidiasis. Due to the low incidence of pulmonary tuberculosis (TB) in Chile, limited numbers of patients with chronic pulmonary aspergillosis are likely: a total of 1212, 25% following TB. Invasive aspergillosis is estimated to affect 296 patients following leukaemia therapy, transplantation and chronic obstructive pulmonary disease (COPD), 1.7/100,000. In addition, allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) were estimated to be around 97.9/100,000 and 127/100,000 respectively, in 675,772 adult asthmatics and 1700 CF patients. Given a 38,000 human immunodeficiency virus (HIV) population, with around 2189 new cases of acquired immune deficiency syndrome (AIDS) annually, cryptococcal meningitis and Pneumocystis pneumonia are estimated at 0.12/100,000 and 4.3/100,000, respectively. In total, 325,000 (1.9%) people in Chile develop serious fungal infections annually. Respiratory fungal disease predominates in Chile; a national action plan for fungal disease is urgently needed, including epidemiological studies to validate the estimates.

  1. Serious fungal infections in Ecuador.

    PubMed

    Zurita, J; Denning, D W; Paz-Y-Miño, A; Solís, M B; Arias, L M

    2017-02-04

    There is a dearth of data from Ecuador on the burden of life-threatening fungal disease entities; therefore, we estimated the burden of serious fungal infections in Ecuador based on the populations at risk and available epidemiological databases and publications. A full literature search was done to identify all epidemiology papers reporting fungal infection rates. WHO, ONU-AIDS, Index Mundi, Global Asthma Report, Globocan, and national data [Instituto Nacional de Estadística y Censos (INEC), Ministerio de Salud Pública (MSP), Sociedad de Lucha Contra el Cáncer (SOLCA), Instituto Nacional de Donación y Trasplante de Órganos, Tejidos y Células (INDOT)] were reviewed. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Ecuador has a variety of climates from the cold of the Andes through temperate to humid hot weather at the coast and in the Amazon basin. Ecuador has a population of 15,223,680 people and an average life expectancy of 76 years. The median estimate of the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) population at risk for fungal disease (<200 CD4 cell counts) is ∼10,000, with a rate of 11.1% (1100) of histoplasma, 7% (700) of cryptococcal meningitis, and 11% (1070) of Pneumocystis pneumonia. The burden of candidemia is 1037. Recurrent Candida vaginitis (≥4 episodes per year) affects 307,593 women aged 15-50 years. Chronic pulmonary aspergillosis probably affects ∼476 patients following tuberculosis (TB). Invasive aspergillosis is estimated to affect 748 patients (∼5.5/100,000). In addition, allergic bronchopulmonary aspergillosis (ABPA) in asthma and severe asthma with fungal sensitization (SAFS) were estimated to affect 26,642 and 45,013 people, respectively. Our estimates indicate that 433,856 (3%) of the population in Ecuador is affected by serious fungal infection.

  2. Fungal nail infection

    MedlinePlus

    ... Common fungal infections include: Athlete's foot Jock itch Ringworm on the skin of the body or head ... fungal infection. Alternative Names Nails - fungal infection; Onychomycosis; Tinea unguium Images Nail infection, candidal Yeast and mold ...

  3. Knockdown of p54nrb inhibits migration, invasion and TNF-α release of human acute monocytic leukemia THP1 cells.

    PubMed

    Zhang, Xiujuan; Wu, Changli; Xiong, Wei; Chen, Chunling; Li, Rong; Zhou, Guangji

    2016-06-01

    54 kDa nuclear RNA- and DNA-binding protein (p54nrb) which is also called non-POU domain-containing octamer-binding protein (NONO) is known to be multifunctional involved in many nuclear processes. It was shown that p54nrb/NONO was closely related to the occurrence of erythroleukemia. Whether p54nrb/NONO plays a role in progress of human acute monocytic leukemia remains unknown. In the present study, we examined the effects of p54nrb/NONO silencing on the biological characteristics of human acute monocytic leukemia THP1 cells. The results showed that p54nrb was strongly expressed in THP1 cells, and knockdown of p54nrb slightly promoted proliferation and strongly inhibited motility and invasion of THP1 cells. Moreover, knockdown of p54nrb strongly decreased the release of TNF-α from THP1 cells by inhibiting certain process of TNF-α secretion, specially for the release of TNF-α induced by lipopolysaccharide (LPS). Notably, the infection of negative control shRNA-containing lentiviruses promoted the migration and the release of TNF-α induced by LPS in THP1 cells. All the above results demonstrated that p54nrb slightly inhibited THP1 cell proliferation, but significantly promoted migration, invasion and release of TNF-α induced by LPS in THP1 cells. The present study indicates that p54nrb is a powerful molecule involved in the regulation of cell motility and promotes the migration and invasion of THP1 cells, and it is more likely to be involved in the release of inflammatory mediators and the motility of inflammatory cells.

  4. The burden of serious fungal diseases in Russia.

    PubMed

    Klimko, N; Kozlova, Y; Khostelidi, S; Shadrivova, O; Borzova, Y; Burygina, E; Vasilieva, N; Denning, D W

    2015-10-01

    The incidence and prevalence of fungal infections in Russia is unknown. We estimated the burden of fungal infections in Russia according to the methodology of the LIFE program (www.LIFE-worldwide.org). The total number of patients with serious and chronic mycoses in Russia in 2011 was three million. Most of these patients (2,607,494) had superficial fungal infections (recurrent vulvovaginal candidiasis, oral and oesophageal candidiasis with HIV infection and tinea capitis). Invasive and chronic fungal infections (invasive candidiasis, invasive and chronic aspergillosis, cryptococcal meningitis, mucormycosis and Pneumocystis pneumonia) affected 69,331 patients. The total number of adults with allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation was 406,082.

  5. Fatal Breakthrough Mucormycosis in an Acute Myelogenous Leukemia Patient while on Posaconazole Prophylaxis.

    PubMed

    Kang, Seung Hun; Kim, Hyun Seon; Bae, Myoung Nam; Kim, Jihye; Yoo, Ji Yeon; Lee, Kwan Yong; Lee, Dong-Gun; Kim, Hee-Je

    2015-03-01

    Posaconazole is a new oral triazole with broad-spectrum antifungal activity. Posaconazole has also shown a significant advantage of preventing invasive fungal infection compared to fluconazole or itraconazole in patients with prolonged neutropenia. Indeed, posaconazole has been commonly used for antifungal prophylaxis in patients undergoing remission induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. We experienced a case of fatal mucormycosis despite posaconazole prophylaxis. To our knowledge, this is the first reported case of fatal breakthrough mucormycosis in a patient receiving posaconazole prophylaxis during remission induction chemotherapy in Korea. This case demonstrated that breakthrough fungal infection can occurs in patients receiving posaconazole prophylaxis because of its limited activity against some mucorales.

  6. [Guidelines for fungal diagnoses and antifungal sensitivity studies].

    PubMed

    Gadea, Ignacio; Cuenca-Estrella, Manuel

    2004-01-01

    The guidelines presented herein, which are based on the indications established by various studies and expert opinions, analyze several issues related to laboratory diagnosis of invasive fungal infections in immunosuppressed patients.

  7. The burden of fungal disease in Denmark.

    PubMed

    Mortensen, Klaus L; Denning, David W; Arendrup, Maiken C

    2015-10-01

    The aim of this study is to calculate the burden of fungal disease in Denmark. We identified all published epidemiology papers reporting fungal infection rates in Denmark. Where no data existed, we used numbers of specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Approximately, one in six Danes will suffer from a fungal infection each year, most of which are skin or mucosal diseases causing disability but no deaths. Good data exist on candidaemia where a national voluntary reporting system is in place and have shown a high rate (9.6 per 100,000 inhabitants) compared other European countries. We present estimates of invasive aspergillosis and chronic pulmonary aspergillosis with rates of 4.4 per 100,000 and 3.1 per 100,000 inhabitants, respectively. Further studies are needed in order to better ascertain high-burden fungal infections such as recurrent vulvovaginal candidiasis (~1350 cases in 100,000 women) as well as allergic bronchopulmonary aspergillosis (~131 cases in 100,000 inhabitants) and severe asthma with fungal sensitisation (cases in 100,000 inhabitants). In conclusion, more than 93,000 Danes or about 2% of Denmark's population will have a non-trivial fungal infection during 1 year, which underscores the magnitude of the fungal burden.

  8. Burden of serious fungal infections in Nepal.

    PubMed

    Khwakhali, Ushana Shrestha; Denning, David W

    2015-10-01

    There are few reports of serious fungal infections in Nepal though the pathogenic and allergenic fungi including Aspergillus species are common in the atmosphere. Herein, we estimate the burden of serious fungal infections in Nepal. All published papers reporting fungal infection rates from Nepal were identified. When few data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Of the 27.3 M population, about 1.87% was estimated to suffer from serious fungal infections annually. We estimated the incidence of fungal keratitis at 73 per 100,000 annually. Chronic obstructive pulmonary disease is common with 215,765 cases, contributing to 1119 cases of invasive aspergillosis annually. Of 381,822 adult asthma cases, we estimated 9546 patients (range 2673-13,364) develop allergic bronchopulmonary aspergillosis and 12,600 have severe asthma with fungal sensitisation. Based on 26,219 cases of pulmonary tuberculosis, the annual incidence of new chronic pulmonary aspergillosis (CPA) cases was estimated at 1678 with a 5 year period prevalence of 5289, 80% of CPA cases. Of 22,994 HIV patients with CD4 counts <350 not on antiretrovirals, Pneumocystis pneumonia was estimated at 990 cases annually. Cases of oral and oesophageal candidiasis in HIV/AIDS patients were estimated at 10,347 and 2950, respectively. There is a significant burden of serious fungal infections in Nepal. Epidemiological studies are necessary to validate these estimates.

  9. Fungal colonization in soils with different management histories: modeling growth in three-dimensional pore volumes.

    PubMed

    Kravchenko, Alexandra; Falconer, Ruth E; Grinev, Dmitri; Otten, Wilfred

    2011-06-01

    Despite the importance of fungi in soil functioning they have received comparatively little attention, and our understanding of fungal interactions and communities is lacking. This study aims to combine a physiologically based model of fungal growth with digitized images of internal pore volume of samples of undisturbed soil from contrasting management practices to determine the effect of physical structure on fungal growth dynamics. We quantified pore geometries of the undisturbed-soil samples from two contrasting agricultural practices, conventionally plowed (chisel plow) (CT) and no till (NT), and from native-species vegetation land use on land that was taken out of production in 1989 (NS). Then we modeled invasion of a fungal species within the soil samples and evaluated the role of soil structure on the progress of fungal colonization of the soil pore space. The size of the studied pores was > or =110 microm. The dynamics of fungal invasion was quantified through parameters of a mathematical model fitted to the fungal invasion curves. Results indicated that NT had substantially lower porosity and connectivity than CT and NS soils. For example, the largest connected pore volume occupied 79% and 88% of pore space in CT and NS treatments, respectively, while it only occupied 45% in NT. Likewise, the proportion of pore space available to fungal colonization was much greater in NS and CT than in NT treatment, and the dynamics of the fungal invasion differed among the treatments. The relative rate of fungal invasion at the onset of simulation was higher in NT samples, while the invasion followed a more sigmoidal pattern with relatively slow invasion rates at the initial time steps in NS and CT samples. Simulations allowed us to elucidate the contribution of physical structure to the rates and magnitudes of fungal invasion processes. It appeared that fragmented pore space disadvantaged fungal invasion in soils under long-term no-till, while large connected pores in

  10. Immunity of fungal infections alleviated graft reject in liver transplantation compared with non-fungus recipients

    PubMed Central

    Xing, Tonghai; Zhong, Lin; Lin, Lihui; Qiu, Guoqiang; Peng, Zhihai

    2015-01-01

    Objective: To evaluate of the immune tolerance in adult LT recipients with Invasive fungal infections (IFIs). Methods: 109 consecutive LT recipients who received LT were included. Percentage of T subsets (CD4+CD25hiCD127- T cells, CD4+CD25loCD45RA+ T cells, CD4+CD25loCD45RA- and CD4+CD45RA-CD45RO+ T cells populations), levels of cytokines (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, IL-12p70, IL-17, TNF-α, TNF-β and GM-CSF) were detected by FACS and Bioplex in peripheral blood. Biopsy specimens were fixed, monoclonal antibodies against CD4, Foxp3 and IL-17 were applied to the above sections and FISH was performed. Results: The risk of acute rejection was decreased in fungal infected liver transplant recipients comparing with non-fungal infected group. CD4+CD25hiCD127T cell population was increased in peripheral blood and memory CD4+CD45RA-CD45RO+ T cell population decreased. There was significant lower levels observed in naïve CD4+CD25loCD45RA+ and CD4+CD25loCD45RA- T cell populations in fungal infected liver transplant. Moreover, IL-2, IL-6, IL-10 and GM-CSF were decreased. However, no significant difference with IL-4 and IL-8 in serum in two infected LT recipients. Conclusion: The incidence of graft rejection in liver transplantation recipients with fungal infections was lower than the non-fungal group. It is important to assess the risk during pretransplant and postoperation for liver transplantation. PMID:26045766

  11. Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision

    PubMed Central

    Bansal, Aditya; Bhama, Jay K.; Patel, Rajan; Desai, Sapna; Mandras, Stacy A.; Patel, Hamang; Collins, Tyrone; Reilly, John P.; Ventura, Hector O.; Parrino, P. Eugene

    2016-01-01

    Background: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. Methods: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. Results: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. Conclusion

  12. Systems Biology of Fungal Infection

    PubMed Central

    Horn, Fabian; Heinekamp, Thorsten; Kniemeyer, Olaf; Pollmächer, Johannes; Valiante, Vito; Brakhage, Axel A.

    2012-01-01

    Elucidation of pathogenicity mechanisms of the most important human-pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections. A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviors in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions. We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modeling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy. PMID:22485108

  13. Core curriculum illustration: invasive fungal sinusitis.

    PubMed

    Desai, Khanant; Nunez, Diego B; Potter, Christopher A

    2017-01-30

    This is the 27th installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for Study online at http://www.erad.org/?page=CCIP_TOC .

  14. [Fungal infections in children with malignant disease].

    PubMed

    Michel, G

    2011-05-01

    Intensified chemotherapy and hematopoietic stem cell transplantation result in severe and prolonged granulocytopenia with an increased risk of invasive fungal infections. The major fungal species that cause serious infections in cancer patients are Candida species and Aspergillus species. The main features of Candida infection in this context are oropharyngeal candidiasis and Candida esophagitis, chronic disseminated candidiasis, also known as hepatosplenic candidiasis, and candidemia. Aspergillus can cause severe lung infection but also sinusal or CNS infection. Because invasive fungal infections are severe and often life-threatening, preventive and empirical managements have become standard practice. An increasing number of antifungal drugs is now available, notably lipid formulations of amphotericin B (liposomal amphotericin B), new azoles with broad spectrum of activity and echinocandin.

  15. Mammary Gland Pathology Subsequent to Acute Infection with Strong versus Weak Biofilm Forming Staphylococcus aureus Bovine Mastitis Isolates: A Pilot Study Using Non-Invasive Mouse Mastitis Model

    PubMed Central

    Gogoi-Tiwari, Jully; Williams, Vincent; Waryah, Charlene Babra; Costantino, Paul; Al-Salami, Hani; Mathavan, Sangeetha; Wells, Kelsi; Tiwari, Harish Kumar; Hegde, Nagendra; Isloor, Shrikrishna; Al-Sallami, Hesham; Mukkur, Trilochan

    2017-01-01

    Background Biofilm formation by Staphylococcus aureus is an important virulence attribute because of its potential to induce persistent antibiotic resistance, retard phagocytosis and either attenuate or promote inflammation, depending upon the disease syndrome, in vivo. This study was undertaken to evaluate the potential significance of strength of biofilm formation by clinical bovine mastitis-associated S. aureus in mammary tissue damage by using a mouse mastitis model. Methods Two S. aureus strains of the same capsular phenotype with different biofilm forming strengths were used to non-invasively infect mammary glands of lactating mice. Biofilm forming potential of these strains were determined by tissue culture plate method, ica typing and virulence gene profile per detection by PCR. Delivery of the infectious dose of S. aureus was directly through the teat lactiferous duct without invasive scraping of the teat surface. Both bacteriological and histological methods were used for analysis of mammary gland pathology of mice post-infection. Results Histopathological analysis of the infected mammary glands revealed that mice inoculated with the strong biofilm forming S. aureus strain produced marked acute mastitic lesions, showing profuse infiltration predominantly with neutrophils, with evidence of necrosis in the affected mammary glands. In contrast, the damage was significantly less severe in mammary glands of mice infected with the weak biofilm-forming S. aureus strain. Although both IL-1β and TNF-α inflammatory biomarkers were produced in infected mice, level of TNF-α produced was significantly higher (p<0.05) in mice inoculated with strong biofilm forming S. aureus than the weak biofilm forming strain. Conclusion This finding suggests an important role of TNF-α in mammary gland pathology post-infection with strong biofilm-forming S. aureus in the acute mouse mastitis model, and offers an opportunity for the development of novel strategies for reduction of

  16. A retrospective analysis of the use of caspofungin in recipients of liver transplant with a modified high index of suspicion for fungal infection. A critical review of mortality, acute cellular rejection, infections, and changes in the liver function tests while on caspofungin.

    PubMed

    Doria, Cataldo; Bodzin, Adam S; Vaccino, Silvia; Daskalakis, Constantine; Krawitz, Steven; Ramirez, Carlo B

    2011-01-01

    This study is a retrospective analysis of death, adverse events (AE), fungal infections, and hepatic function among recipients of liver transplantation at high risk of fungal infection who received prophylactic treatment with caspofungin. After reviewing data of 105 patients who had received isolated liver transplant between January 2003 and April 2007, we identified and analyzed 82 high-risk patients. Post-transplant patients at high risk for fungal infection are commonly defined by the presence of at least one of the following: (i) re-transplantation; (ii) re-operation; (iii) renal dysfunction. However, in our practice, patients are also considered at high risk for developing fungal infections if they present with the following: (iv) fever of unknown origin; (v) hypothermia; (vi) positive random culture for fungus at the time of transplant (bile and/or ascites); (vii) sepsis; (viii) use of vasopressors; (ix) re-intubation, during the first hospitalization after liver transplant; (x) prolonged intubation (>24 h), and (xi) acute respiratory distress syndrome, until negative fungal cultures are obtained. Exact conditional logistic regression was used to compare the risk of death, AEs, and fungal infections between patients who received caspofungin, other antifungal drugs, and no antifungal drugs. Analyses were then performed with SAS 9.1 (SAS Institute Inc., Cary, NC, USA). Patients were between 27 and 72 yr old (mean = 55), with two-thirds male and three-quarters Caucasian. Sixteen patients received caspofungin (11 preventively), and 32 received other antifungal (26 preventively). There were no proven fungal infections among the patients who received caspofungin, three infections among patients who received other antifungal (3/26 = 12%), and 14 infections among patients who were not preventively treated (14/45 = 31%). These infection rates were significantly different across the three groups (p = 0.029), with caspofungin and other antifungal preventive treatment

  17. Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN38327949

    PubMed Central

    Besselink, Marc GH; van Santvoort, Hjalmar C; Nieuwenhuijs, Vincent B; Boermeester, Marja A; Bollen, Thomas L; Buskens, Erik; Dejong, Cornelis HC; van Eijck, Casper HJ; van Goor, Harry; Hofker, Sijbrand S; Lameris, Johan S; van Leeuwen, Maarten S; Ploeg, Rutger J; van Ramshorst, Bert; Schaapherder, Alexander FM; Cuesta, Miguel A; Consten, Esther CJ; Gouma, Dirk J; van der Harst, Erwin; Hesselink, Eric J; Houdijk, Lex PJ; Karsten, Tom M; van Laarhoven, Cees JHM; Pierie, Jean-Pierre EN; Rosman, Camiel; Bilgen, Ernst Jan Spillenaar; Timmer, Robin; van der Tweel, Ingeborg; de Wit, Ralph J; Witteman, Ben JM; Gooszen, Hein G

    2006-01-01

    Background The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis. PMID:16606471

  18. Temporal trends in the use of invasive cardiac procedures for non-ST segment elevation acute coronary syndromes according to initial risk stratification

    PubMed Central

    Jedrzkiewicz, Sean; Goodman, Shaun G; Yan, Raymond T; Welsh, Robert C; Kornder, Jan; DeYoung, J Paul; Wong, Graham C; Rose, Barry; Grondin, François R; Gallo, Richard; Huang, Wei; Gore, Joel M; Yan, Andrew T

    2009-01-01

    BACKGROUND: Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that high-risk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada. OBJECTIVE: To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS. METHODS: Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment. RESULTS: While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and high-risk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization. CONCLUSION: Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada. PMID:19898699

  19. Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema

    PubMed Central

    Crane, S; Elliott, M; Gilligan, P; Richards, K; Gray, A

    2004-01-01

    Background: Continuous positive airways pressure (CPAP) and bilevel non-invasive ventilation may have beneficial effects in the treatment of patients with acute cardiogenic pulmonary oedema. The efficacy of both treatments was assessed in the UK emergency department setting, in a randomised comparison with standard oxygen therapy. Methods: Sixty patients presenting with acidotic (pH<7.35) acute, cardiogenic pulmonary oedema, were randomly assigned conventional oxygen therapy, CPAP (10 cm H2O), or bilevel ventilation (IPAP 15 cm H2O, EPAP 5 cm H2O) provided by a standard ventilator through a face mask. The main end points were treatment success at two hours and in-hospital mortality. Analyses were by intention to treat. Results: Treatment success (defined as all of respiratory rate<23 bpm, oxygen saturation of>90%, and arterial blood pH>7.35 (that is, reversal of acidosis), at the end of the two hour study period) occurred in three (15%) patients in the control group, seven (35%) in the CPAP group, and nine (45%) in the bilevel group (p = 0.116). Fourteen (70%) of the control group patients survived to hospital discharge, compared with 20 (100%) in the CPAP group and 15 (75%) in the bilevel group (p = 0.029; Fisher's test). Conclusions: In this study, patients presenting with acute cardiogenic pulmonary oedema and acidosis, were more likely to survive to hospital discharge if treated with CPAP, rather than with bilevel ventilation or with conventional oxygen therapy. There was no relation between in hospital survival and early physiological changes. Survival rates were similar to other studies despite a low rate of endotracheal intubation. PMID:14988338

  20. Serious fungal infections in Thailand.

    PubMed

    Chayakulkeeree, M; Denning, D W

    2017-02-04

    The burden of serious fungal infection in Thailand is increasing but data regarding its incidence and prevalence are lacking. In this study we aimed to estimate the burden of serious fungal diseases in Thailand based on the size of the populations at risk and available epidemiological databases. Data derived from The Bureau of Epidemiology, Department of Disease Control, Thai Ministry of Public Health, World Health Organisation, international and local reports, and some unreported data were used. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE. Recurrent vulvovaginal candidiasis (>4 episodes per year) is estimated to occur in 3,310 per 100,000 population. Using a previously described rate that 14/10,000 admissions are with fungaemia and 94% of those are Candida, we estimated 8,650 patients with candidaemia. The prevalence of chronic pulmonary aspergillosis is relatively high with a total of 19,044, approximately half subsequent to pulmonary tuberculosis. Invasive aspergillosis is estimated to affect 941 patients following leukaemia therapy, transplantations, and chronic obstructive pulmonary disease, approximately 1.4/100,000. In addition, allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation were estimated at approximately 58.4/100,000 and 77/100,000, respectively. Given approximately 8,134 new cases of AIDS annually, cryptococcal meningitis, Pneumocystis pneumonia, and Talaromyces marneffei infection are estimated at 1.9/100,000, 2.6/100,000, and 0.3/100,000, respectively. The present study indicates that about 1.93% (1,254,562) of the population is affected by serious fungal infections. Owing to the lack of data, reports, and statistics, the number of patients with mycoses in Thailand can only be estimated.

  1. Application of fiberoptic bronchscopy in patients with acute exacerbations of chronic obstructive pulmonary disease during sequential weaning of invasive-noninvasive mechanical ventilation

    PubMed Central

    Song, Rong-rong; Qiu, Yan-ping; Chen, Yong-ju; Ji, Yong

    2012-01-01

    BACKGROUND: Early withdrawal of invasive mechanical ventilation (IMV) followed by noninvasive MV (NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with acute respiratory failure (ARF). Using pulmonary infection control window (PIC window) as the switch point for transferring from invasive to noninvasive MV, the time for early extubation can be more accurately judged, and therapy efficacy can be improved. This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy (FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV. METHODS: Since July 2006 to January 2011, 106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization. Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used (group A, n=54) or not (group B, n=52) during sequential weaning from invasive to noninvasive MV. In group A, for sputum suction and bronchoalveolar lavage (BAL), a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube, which was accompanied with uninterrupted use of a ventilator. After achieving PIC window, patients of both groups changed to NIMV mode, and weaned from ventilation. The following listed indices were used to compare between the groups after treatment: 1) the occurrence time of PIC, the duration of MV, the length of ICU stay, the success rate of weaning from MV for the first time, the rate of reventilation and the occurrence rate of ventilator-associated pneumonia (VAP); 2) the convenience and safety of FOB manipulation. The results were compared using Student’s t test and the Chi-square test. RESULTS: The occurrence time of PIC was (5.01±1.49) d, (5.87±1.87) d in groups A and B, respectively (P<0.05); the duration of MV was (6.98±1.84) d, (8.69±2.41) d in groups A and B, respectively (P<0.01); the

  2. Allergic fungal sinusitis in children.

    PubMed

    Thorp, Brian D; McKinney, Kibwei A; Rose, Austin S; Ebert, Charles S

    2012-06-01

    Allergic fungal sinusitis (AFS) is a subtype of eosinophilic chronic rhinosinusitis (CRS) characterized by type I hypersensitivity, nasal polyposis, characteristic computed tomography scan findings, eosinophilic mucus, and the presence of fungus on surgical specimens without evidence of tissue invasion. This refractory subtype of CRS is of the great interest in the pediatric population, given the relatively early age of onset and the difficulty in managing AFS through commercially available medical regimens. Almost universally, a diagnosis of AFS requires operative intervention. Postoperative adjuvant medical therapy is a mainstay in the treatment paradigm of pediatric AFS.

  3. Determination of the acute toxicity of isoniazid to three invasive carp species and rainbow trout in static exposures

    USGS Publications Warehouse

    Schreier, Theresa M.; Hubert, Terrance D.

    2015-01-01

    Three invasive fishes of considerable concern to aquatic resource managers are the Hypophthalmichthys nobilis (bighead carp),Hypophthalmichthys molitrix (silver carp), and Ctenopharyngodon idella (grass carp), collectively known as Asian carps. There is a need for an effective chemical control agent for Asian carps. Isoniazid was identified as a potential toxicant for grass carp. The selective toxicity of isoniazid to grass carp was verified as a response to an anecdotal report received in 2013. In addition, the toxicity of isoniazid to bighead carp, silver carp, and Oncorhynchus mykiss (rainbow trout) was evaluated. Isoniazid was not toxic to grass carp at the reported anecdotal concentration, which was 13 milligrams per liter. Isoniazid (130 milligrams per liter) was not selectively toxic to bighead carp, silver carp, or grass carp when compared to rainbow trout.

  4. Pulmonary Injury after Combined Exposures to Low-Dose Low-LET Radiation and Fungal Spores

    PubMed Central

    Marples, B.; Downing, L.; Sawarynski, K. E.; Finkelstein, J. N.; Williams, J. P.; Martinez, A. A.; Wilson, G. D.; Sims, M. D.

    2013-01-01

    Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury. PMID:21275606

  5. Antimicrobial Peptides as a Strategy to Combat Fungal Biofilms.

    PubMed

    Delattin, Nicolas; Brucker, Katrijn De; Cremer, Kaat De; Cammue, Bruno P A; Thevissen, Karin

    2017-01-01

    Invasive fungal infections caused by opportunistic fungal pathogens are associated with high mortality rates, mainly due to the occurrence of genotypic and/or phenotypic resistance. One of the causes of phenotypic resistance is the preferred growth of various fungal pathogens as biofilms, which are tolerant or resistant to most classes of antifungal agents. Moreover, increasing evidence points to biofilm formation as a general prerequisite for the development of systemic infections. Therefore, new antibiofilm agents are urgently needed to reduce the incidence of biofilm-associated infections. Nowadays, antimicrobial peptides (AMPs) are considered as valuable alternatives for or complements to the classical antifungal agents to combat fungal infections. Many review reports describe activity of AMPs against free-living planktonic fungal pathogens. In contrast, this review summarizes the antibiofilm properties of natural or synthetic AMPs against fungal biofilms and their potential to enhance the antibiofilm activity of existing antifungal agents.

  6. Isavuconazonium sulfate for the treatment of fungal infection.

    PubMed

    Walker, R C; Zeuli, J D; Temesgen, Z

    2016-01-01

    Isavuconazole is a new azole antifungal drug with a broad antifungal spectrum that includes yeasts, molds and dimorphic fungi. Its prodrug, isavuconazonium sulfate, is currently approved in the United States and Europe for the treatment of the two of the most common and most challenging invasive fungal infections in clinical practice, invasive aspergillosis and invasive mucormycosis. It is available in both oral and intravenous formulations for once-a-day dosing and has favorable safety profile and drug interaction potential in comparison to voriconazole. Its role in the treatment of other fungal infections, besides aspergillosis and mucormycosis, remains to be determined. Similarly, its efficacy in prophylaxis against invasive fungal infections or its utility in patients with prior azole exposure is yet to be elucidated in clinical studies.

  7. Genetic Susceptibility to Fungal Infections in Humans.

    PubMed

    Lionakis, Michail S

    2012-03-01

    Most fungal infections in humans occur in the setting of iatrogenic immunosuppression or HIV infection. In the absence of these factors, fungi cause mild, self-limited infections that typically involve mucocutaneous surfaces. Hence, when persistent or recurrent mucocutaneous infections (chronic mucocutaneous candidiasis [CMC]) or invasive fungal infections (IFIs) develop in a "normal" host, they are indicative of genetic defects causing innate or adaptive immune dysfunction. In this review, recent developments concerning genetic and immunologic factors that affect the risk for IFIs and CMC are critically discussed.

  8. Genetic Susceptibility to Fungal Infections in Humans

    PubMed Central

    Lionakis, Michail S.

    2012-01-01

    Most fungal infections in humans occur in the setting of iatrogenic immunosuppression or HIV infection. In the absence of these factors, fungi cause mild, self-limited infections that typically involve mucocutaneous surfaces. Hence, when persistent or recurrent mucocutaneous infections (chronic mucocutaneous candidiasis [CMC]) or invasive fungal infections (IFIs) develop in a “normal” host, they are indicative of genetic defects causing innate or adaptive immune dysfunction. In this review, recent developments concerning genetic and immunologic factors that affect the risk for IFIs and CMC are critically discussed. PMID:23087779

  9. Estimated burden of fungal infections in Germany.

    PubMed

    Ruhnke, Markus; Groll, Andreas H; Mayser, Peter; Ullmann, Andrew J; Mendling, Werner; Hof, Herbert; Denning, David W

    2015-10-01

    In the late 1980's, the incidence of invasive fungal diseases (IFDs) in Germany was estimated with 36.000 IFDs per year. The current number of fungal infections (FI) occurring each year in Germany is still not known. In the actual analysis, data on incidence of fungal infections in various patients groups at risk for FI were calculated and mostly estimated from various (mostly national) resources. According to the very heterogenous data resources robust data or statistics could not be obtained but preliminary estimations could be made and compared with data from other areas in the world using a deterministic model that has consistently been applied in many countries by the LIFE program ( www.LIFE-worldwide.org). In 2012, of the 80.52 million population (adults 64.47 million; 41.14 million female, 39.38 million male), 20% are children (0-14 years) and 16% of population are ≥65 years old. Using local data and literature estimates of the incidence or prevalence of fungal infections, about 9.6 million (12%) people in Germany suffer from a fungal infection each year. These figures are dominated (95%) by fungal skin disease and recurrent vulvo-vaginal candidosis. In general, considerable uncertainty surrounds the total numbers because IFDs do not belong to the list of reportable infectious diseases in Germany and most patients were not hospitalised because of the IFD but a distinct underlying disease.

  10. Burden of fungal infections in Senegal.

    PubMed

    Badiane, Aida S; Ndiaye, Daouda; Denning, David W

    2015-10-01

    Senegal has a high rate of tuberculosis and a low HIV seropositivity rate and aspergilloma, life-threatening fungal infections, dermatophytosis and mycetoma have been reported in this study. All published epidemiology papers reporting fungal infection rates from Senegal were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in each to estimate national incidence or prevalence. The results show that tinea capitis is common being found in 25% of children, ~1.5 million. About 191,000 Senegalese women get recurrent vaginal thrush, ≥4 times annually. We estimate 685 incident cases of chronic pulmonary aspergillosis (CPA) following TB and prevalence of 2160 cases. Asthma prevalence in adults varies from 3.2% to 8.2% (mean 5%); 9976 adults have allergic bronchopulmonary aspergillosis (ABPA) and 13,168 have severe asthma with fungal sensitisation (SAFS). Of the 59,000 estimated HIV-positive patients, 366 develop cryptococcal meningitis; 1149 develop Pneumocystis pneumonia and 1946 develop oesophageal candidiasis, in which oral candidiasis (53%) and dermatophytosis (16%) are common. Since 2008-2010, 113 cases of mycetoma were diagnosed. In conclusion, we estimate that 1,743,507 (12.5%) people in Senegal suffer from a fungal infection, excluding oral candidiasis, fungal keratitis, invasive candidiasis or aspergillosis. Diagnostic and treatment deficiencies should be rectified to allow epidemiological studies.

  11. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2017-02-13

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  12. Primary antifungal prophylaxis in acute myeloblastic leukemia and myelodysplastic syndrome--still an open question?

    PubMed

    Rüping, Maria J G T; Vehreschild, Jörg J; Cornely, Oliver A

    2010-01-01

    In this review, we aim to compare different early treatment strategies of invasive fungal diseases in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Three treatment approaches--prophylactic, empiric, and preemptive treatment--are subject to continuous discussion among physicians treating patients at risk. Considering the available clinical basis of evidence, we opt for antifungal prophylaxis with posaconazole 200 mg tid po as our primary prophylactic strategy, while the employment of preemptive treatment should be delayed until more accurate diagnostic tools become available. In addition to antifungal prophylaxis, empiric treatment with caspofungin or L-AmB may be administered to patients with fever resistant to broad-spectrum antibiotic treatment and without radiographic findings typical of invasive fungal disease.

  13. Sleep-related breathing disorders in acute respiratory failure assisted by non-invasive ventilatory treatment: utility of portable polysomnographic system.

    PubMed

    Resta, O; Guido, P; Foschino Barbaro, M P; Picca, V; Talamo, S; Lamorgese, V

    2000-02-01

    PAP, Respironics Inc.) airway positive pressure in timed or spontaneous/timed modes. Two patients required intubation and mechanical ventilatory treatment. In one patient with hypothyroidism was sufficient to institute hormonal therapy. Our study shows that acute respiratory failure due to SRBD is not exceptional in an Intermediate Intensive Care Unit and that if clinical suspicion is strong, portable polysomnography may yield diagnostic confirmation and help in establishing appropriate treatment and in avoiding the invasive ventilatory treatment.

  14. Non-invasive ventilation (NIV) in the clinical management of acute COPD in 233 UK hospitals: results from the RCP/BTS 2003 National COPD Audit.

    PubMed

    Kaul, Sundeep; Pearson, Michael; Coutts, Ian; Lowe, Derek; Roberts, Michael

    2009-06-01

    Non-invasive ventilation (NIV) is a clinically proven, cost-effective intervention for acidotic exacerbations of COPD that is recommended by UK national guidelines. This study examines the extent to which these recommendations are being followed in the UK. Between August and October 2003 a national audit of COPD exacerbations was conducted by the Royal College of Physicians and the British Thoracic Society. 233 (94%) UK hospitals submitted data for 7,529 prospectively recruited acute COPD admissions, documenting process of care and outcomes from a retrospective case note audit. They also completed a resources and organisation of care proforma. Nineteen hospitals (8%) reported they did not offer NIV. There was no access to NIV in 92 (39%) intensive care units in 88 (36%), high-dependency units or on general wards of 85 (34%) hospitals. In 74 (30%) NIV was available on all 3 sites. A low pH (<7.35) was noted at some time during admission for 26% (1714/6544) of patients and NIV was administered to 31%. Patients receiving NIV were more often admitted under a respiratory physician, or seen at some stage by a respiratory specialist and had more severe disease (higher PaCO2 (median 9.8 v 7.8 kPa), lower oxygen tension (median 8.8 v 9.8 kPa), higher incidence of peripheral oedema (48% v 39%), of pneumonia (27% v 16%), higher in-hospital mortality (26% v 14%) and at 90 days (37% v 24%) and longer hospital stays (median 9 v 7 days) than those not receiving NIV. Hospitals with least usage of NIV had similar mortality rates to those using NIV more often. A comprehensive NIV service is not available in many hospitals admitting patients with acute respiratory failure secondary to COPD. Access to acute NIV is inadequate and does not conform with NICE and BTS guidelines. These observational audit data do not demonstrate benefits of NIV on survival when compared to conventional management, contrary to results from randomised trials. Reasons for this are unclear but unmeasured

  15. Burden of fungal infections in Qatar.

    PubMed

    Taj-Aldeen, Saad J; Chandra, Prem; Denning, David W

    2015-10-01

    Few estimates of fungal disease frequency have been attempted in the Middle East. We have estimated the burden of fungal infections in Qatar. The aim of the study was to compute and determine the burden of serious fungal infections, in an attempt to estimate fungal disease frequency, which has not previously been attempted in this country. Disease statistics were collected from the Microbiology laboratory database and from 2011 WHO statistics. The data are expressed per 100,000 populations. The reported cases of candidaemia rose to 288 with an estimated rate of 15.4/100,000. A real increase in the burden of candidaemia was found over that previously reported (12.9/100,000) for the years 2004-2009. Candida peritonitis was estimated in 8.02 cases/100,000 population. Recurrent (≥4 year(-1) ) vaginal infections affect at least 32,782 women with a rate of 3506/100,000 inhabitants. Severe asthma with fungal sensitisation affected 1486 people, allergic bronchopulmonary aspergillosis 1126 people and chronic pulmonary aspergillosis 176 people. Rhinosinusitis, mucormycosis and Fusarium infection occurred at rates of 2.31, 1.23, 1.86 cases/100,000 respectively. The estimated rate of invasive aspergillosis was very low (0.6/100,000). Low rates of Cryptococcus meningitis and Pneumocystis pneumonia are attributable to low HIV infection rates. In conclusion, fungal infections are increasingly reported, especially candidaemia. Surveillance and guidelines are needed to optimise care and management of common fungal infections. In addition, a fungal registry system needs development for surveillance.

  16. Non-invasive ventilation with bubble CPAP is feasible and improves respiratory physiology in hospitalised Malawian children with acute respiratory failure

    PubMed Central

    Walk, J.; Dinga, P.; Banda, C.; Msiska, T.; Chitsamba, E.; Chiwayula, N.; Lufesi, N.; Mlotha-Mitole, R.; Costello, A.; Phiri, A.; Colbourn, T.; McCollum, E. D.; Lang, H. J.

    2015-01-01

    Background In low-income countries and those with a high prevalence of HIV, respiratory failure is a common cause of death in children. However, the role of non-invasive ventilation with bubble continuous positive airway pressure (bCPAP) in these patients is not well established. Methods A prospective observational study of bCPAP was undertaken between July and September 2012 in 77 Malawian children aged 1 week to 14 years with progressive acute respiratory failure despite oxygen and antimicrobial therapy. Results Forty-one (53%) patients survived following bCPAP treatment, and an HIV-uninfected single-organ disease subgroup demonstrated bCPAP success in 14 of 17 (82%). Compared with children aged ≥60 months, infants of 0–2 months had a 93% lower odds of bCPAP failure (odds ratio 0.07, 95% confidence interval 0.004–1.02, P = 0.05). Following commencement of bCPAP, respiratory physiology improved, the average respiratory rate decreased from 61 to 49 breaths/minute (P = 0.0006), and mean oxygen saturation increased from 92.1% to 96.1% (P = 0.02). Conclusions bCPAP was well accepted by caregivers and patients and can be feasibly implemented into a tertiary African hospital with high-risk patients and limited resources. PMID:25434361

  17. Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines.

    PubMed

    Reijtman, Vanesa; Fossati, Sofía; Hernández, Claudia; Sommerfleck, Patricia; Bernáldez, Patricia; Litterio, Mirta; Berberian, Griselda; Regueira, Mabel; Lopardo, Horacio

    2013-01-01

    A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AOM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

  18. Invasive mycoses: diagnostic challenges.

    PubMed

    Ostrosky-Zeichner, Luis

    2012-01-01

    Despite the availability of newer antifungal drugs, outcomes for patients with invasive fungal infections (IFIs) continue to be poor, in large part due to delayed diagnosis and initiation of appropriate antifungal therapy. Standard histopathologic diagnostic techniques are often untenable in at-risk patients, and culture-based diagnostics typically are too insensitive or nonspecific, or provide results after too long a delay for optimal IFI management. Newer surrogate markers of IFIs with improved sensitivity and specificity are needed to enable earlier diagnosis and, ideally, to provide prognostic information and/or permit therapeutic monitoring. Surrogate assays should also be accessible and easy to implement in the hospital. Several nonculture-based assays of newer surrogates are making their way into the medical setting or are currently under investigation. These new or up-and-coming surrogates include antigens/antibodies (mannan and antimannan antibodies) or fungal metabolites (d-arabinitol) for detection of invasive candidiasis, the Aspergillus cell wall component galactomannan used to detect invasive aspergillosis, or the fungal cell wall component and panfungal marker β-glucan. In addition, progress continues with use of polymerase chain reaction- or other nucleic acid- or molecular-based assays for diagnosis of either specific or generic IFIs, although the various methods must be better standardized before any of these approaches can be more fully implemented into the medical setting. Investigators are also beginning to explore the possibility of combining newer surrogate markers with each other or with more standard diagnostic approaches to improve sensitivity, specificity, and capacity for earlier diagnosis, at a time when fungal burden is still relatively low and more responsive to antifungal therapy.

  19. A Comprehensive Evaluation of the Bruker Biotyper MS and Vitek MS Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Systems for Identification of Yeasts, Part of the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study, 2012 to 2013

    PubMed Central

    Wang, He; Fan, Yan-Yan; Kudinha, Timothy; Xu, Zhi-Peng; Xiao, Meng; Zhang, Li; Fan, Xin; Kong, Fanrong

    2016-01-01

    Among the 2,683 yeast isolates representing 41 different species (25 Candida and Candida-related species and 16 non-Candida yeast species) collected in the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program (2012 to 2013), the Bruker Biotyper MS matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) system exhibited significantly higher accuracy rates than the Vitek MS system for identification of all yeast isolates (98.8% versus 95.4%, P <0.001 by Pearson's chi-square test) and for all Candida and Candida-related species isolates (99.4% versus 95.5%, P < 0.001). PMID:26912761

  20. Non–Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double‐Blind, Sham‐Controlled ACT1 Study

    PubMed Central

    Mechtler, Laszlo L.; Kudrow, David B.; Calhoun, Anne H.; McClure, Candace; Saper, Joel R.; Liebler, Eric J.; Rubenstein Engel, Emily; Tepper, Stewart J.

    2016-01-01

    Objective To evaluate non‐invasive vagus nerve stimulation (nVNS) as an acute cluster headache (CH) treatment. Background Many patients with CH experience excruciating attacks at a frequency that is not sufficiently addressed by current symptomatic treatments. Methods One hundred fifty subjects were enrolled and randomized (1:1) to receive nVNS or sham treatment for ≤1 month during a double‐blind phase; completers could enter a 3‐month nVNS open‐label phase. The primary end point was response rate, defined as the proportion of subjects who achieved pain relief (pain intensity of 0 or 1) at 15 minutes after treatment initiation for the first CH attack without rescue medication use through 60 minutes. Secondary end points included the sustained response rate (15‐60 minutes). Subanalyses of episodic cluster headache (eCH) and chronic cluster headache (cCH) cohorts were prespecified. Results The intent‐to‐treat population comprised 133 subjects: 60 nVNS‐treated (eCH, n = 38; cCH, n = 22) and 73 sham‐treated (eCH, n = 47; cCH, n = 26). A response was achieved in 26.7% of nVNS‐treated subjects and 15.1% of sham‐treated subjects (P = .1). Response rates were significantly higher with nVNS than with sham for the eCH cohort (nVNS, 34.2%; sham, 10.6%; P = .008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; P = .48). Sustained response rates were significantly higher with nVNS for the eCH cohort (P = .008) and total population (P = .04). Adverse device effects (ADEs) were reported by 35/150 (nVNS, 11; sham, 24) subjects in the double‐blind phase and 18/128 subjects in the open‐label phase. No serious ADEs occurred. Conclusions In one of the largest randomized sham‐controlled studies for acute CH treatment, the response rate was not significantly different (vs sham) for the total population; nVNS provided significant, clinically meaningful, rapid, and sustained benefits for eCH but not for cCH, which affected

  1. Burden of serious fungal infections in Belgium.

    PubMed

    Lagrou, Katrien; Maertens, Johan; Van Even, Ellen; Denning, David W

    2015-10-01

    We aimed to estimate the total number of serious fungal infections occurring yearly in Belgium. The number of cryptococcal infections was retrieved from the National Reference Center for Mycosis. Populations at risk and fungal infections frequencies in these populations were used to estimate incidence or prevalence of other fungal infections. The Belgian population consists of 11.10 million people. Cryptococcal meningitis is rare. In all, 15 of the 1227 newly diagnosed HIV/AIDS cases presented with Pneumocystis jirovecii pneumonia. This accounts for ±14% of total PCP cases (n = 120). The incidence of candidaemia is estimated as 5/100,000 resulting in 555 cases and 213 deaths. A total number of 675 invasive aspergillosis cases and ≥169 deaths attributed to this infection were calculated. Chronic pulmonary aspergillosis is estimated to be prevalent in 662 cases. Allergic bronchopulmonary aspergillosis cases were estimated to be 23,119 applying a 2.5% and 15% rate in adult asthma and cystic fibrosis patients respectively. Severe asthma with fungal sensitisation cases was estimated to be 30,402. There were 174,760 women with recurrent Candida vaginitis assuming a 6% rate in women aged between 15 and 50. Approximately 233,000 people of the Belgian population (2.1%) are estimated to suffer from a fungal infection on a yearly basis.

  2. Burden of fungal infections in Algeria.

    PubMed

    Chekiri-Talbi, M; Denning, D W

    2017-02-21

    We report for the first time in Algeria and provide burden estimates. We searched for existing data and estimated the incidence and prevalence of fungal diseases based on the population at risk and available epidemiological data. Demographic data were derived from the National Office of Statistics (Office National des Statistiques: ONS), World Health Organization (WHO), The Joint Nations Programme on HIV/AIDS (UNAIDS) and national published reports. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. Algeria has 40.4 million inhabitants, and probably at least 568,900 (1.41%) of Algerians have a serious fungal infection each year. Recurrent vulvovaginal candidiasis (485,000) and fungal asthma (72,000) are probably the commonest problems, as there are over 1 million adult asthmatics. Candidaemia is estimated in 2,020 people, invasive aspergillosis in 2,865 people, and intra-abdominal candidiasis in 303 people; these are the most common life-threatening problems. AIDS is uncommon, but cancer is not (45,000 new cases of cancer including 1,500 in children), nor is COPD (an estimated 317,762 patients, of whom 20.3% are admitted to hospital each year). A focus on improving the diagnosis and epidemiological data related to fungal infection is necessary in Algeria.

  3. Serious fungal infections in Egypt.

    PubMed

    Zaki, S M; Denning, D W

    2017-02-17

    We aimed to estimate the burden of serious fungal infections in Egypt, currently unknown, based on the size of the populations at risk and available epidemiological data. Data were obtained from the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS), and published reports with clearcut denominators. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology. The population of Egypt in 2011 was ∼82,500,000; 31% children, and 8% women >60 years of age. Amongst about 21.8 million women aged 15-50 years, recurrent vulvovaginal candidiasis (≥4 episodes/year) is estimated to occur in 1.3 million (3,169/100,000 females). Using a low international average rate of 5/100,000, we estimate 4,127 cases of candidaemia, and 619 patients with intra-abdominal candidiasis. Amongst the survivors of pulmonary tuberculosis (TB) in Egypt in 2012, 319 new cases of chronic pulmonary aspergillosis (CPA) are likely, a prevalence of 1,005 post-TB and a total prevalence estimate of 3,015 CPA patients in all. Asthma is common in Egypt, affecting 9.4% of adults, 5.35 million, and so ABPA and SAFS were estimated in around 162/100,000 and 214/100,000 respectively. Invasive aspergillosis is estimated to affect 495 patients following leukaemia therapy, there are an estimated 37 cases in renal and liver transplant recipients, and an estimated 132 patients develop IA in the context of lung cancer. Amongst 641,000 COPD admissions to hospital each year, 8,337 patients develop IA. The total HIV-infected population is small, with an estimated 6,500 patients, 2,500 not on antiretroviral therapy. Amongst HIV-infected patients, 38 (0.6%) cases of cryptococcal meningitis and 125 (1.9%) cases of Pneumocystis pneumonia are estimated each year. Fungal keratitis is common, with 28-55% (mean 40%) of corneal infections being fungal, an estimated total of 11,550 cases. The present study indicates

  4. Genetic Susceptibility to Fungal Infections: What is in the Genes?

    PubMed

    Maskarinec, Stacey A; Johnson, Melissa D; Perfect, John R

    2016-06-01

    The development of severe fungal infections has long been associated with traditional risk factors such as profound immunosuppression, yet it remains challenging to understand why under similar conditions only some patients will develop these infections while others will not. Recent studies have demonstrated the importance of host genetic variation in influencing the severity and susceptibility to invasive fungal infections (IFIs). In this review, we examine selected primary immunodeficiencies characterized by their vulnerability to a narrow range of fungal pathogens, and then focus on recently identified genetic polymorphisms associated with an increased susceptibility to IFIs.

  5. Immunological Consequences of Intestinal Fungal Dysbiosis.

    PubMed

    Wheeler, Matthew L; Limon, Jose J; Bar, Agnieszka S; Leal, Christian A; Gargus, Matthew; Tang, Jie; Brown, Jordan; Funari, Vincent A; Wang, Hanlin L; Crother, Timothy R; Arditi, Moshe; Underhill, David M; Iliev, Iliyan D

    2016-06-08

    Compared to bacteria, the role of fungi within the intestinal microbiota is poorly understood. In this study we investigated whether the presence of a "healthy" fungal community in the gut is important for modulating immune function. Prolonged oral treatment of mice with antifungal drugs resulted in increased disease severity in acute and chronic models of colitis, and also exacerbated the development of allergic airway disease. Microbiota profiling revealed restructuring of fungal and bacterial communities. Specifically, representation of Candida spp. was reduced, while Aspergillus, Wallemia, and Epicoccum spp. were increased. Oral supplementation with a mixture of three fungi found to expand during antifungal treatment (Aspergillus amstelodami, Epicoccum nigrum, and Wallemia sebi) was sufficient to recapitulate the exacerbating effects of antifungal drugs on allergic airway disease. Taken together, these results indicate that disruption of commensal fungal populations can influence local and peripheral immune responses and enhance relevant disease states.

  6. Near Infrared Spectroscopy (NIRS) as a New Non-Invasive Tool to Detect Oxidative Skeletal Muscle Impairment in Children Survived to Acute Lymphoblastic Leukaemia

    PubMed Central

    Lanfranconi, Francesca; Pollastri, Luca; Ferri, Alessandra; Fraschini, Donatella; Masera, Giuseppe; Miserocchi, Giuseppe

    2014-01-01

    Background Separating out the effects of cancer and treatment between central and peripheral components of the O2 delivery chain should be of interest to clinicians for longitudinal evaluation of potential functional impairment in order to set appropriate individually tailored training/rehabilitation programmes. We propose a non-invasive method (NIRS, near infrared spectroscopy) to be used in routine clinical practice to evaluate a potential impairment of skeletal muscle oxidative capacity during exercise in children previously diagnosed with acute lymphoblastic leukaemia (ALL). The purpose of this study was to evaluate the capacity of skeletal muscle to extract O2 in 10 children diagnosed with ALL, 1 year after the end of malignancy treatment, compared to a control group matched for gender and age (mean±SD = 7.8±1.5 and 7.3±1.4 years, respectively). Methods and Findings Participants underwent an incremental exercise test on a treadmill until exhaustion. Oxygen uptake (), heart rate (HR), and tissue oxygenation status (Δ[HHb]) of the vastus lateralis muscle evaluated by NIRS, were measured. The results showed that, in children with ALL, a significant linear regression was found by plotting vs Δ[HHb] both measured at peak of exercise. In children with ALL, the slope of the HR vs linear response (during sub-maximal and peak work rates) was negatively correlated with the peak value of Δ[HHb]. Conclusions The present study proves that the NIRS technique allows us to identify large inter-individual differences in levels of impairment in muscle O2 extraction in children with ALL. The outcome of these findings is variable and may reflect either muscle atrophy due to lack of use or, in the most severe cases, an undiagnosed myopathy. PMID:24956391

  7. The use of a prospective audit proforma to improve door-to-mask times for acute exacerbations chronic obstructive pulmonary disease (COPD) requiring non-invasive ventilation (NIV).

    PubMed

    Mandal, S; Howes, T Q; Parker, M; Roberts, C M

    2014-12-01

    Non-invasive ventilation (NIV) is an evidence based management of acidotic, hypercapnic exacerbations of COPD. Previous national and international audits of clinical practice have shown variation against guideline standards with significant delays in initiating NIV. We aimed to map the clinical pathway to better understand delays and reduce the door-to-NIV time to less than 3 hours for all patients with acidotic, hypercapnic exacerbations of COPD requiring this intervention, by mandating the use of a guideline based educational management proforma.The proforma was introduced at 7 acute hospitals in North London and Essex and initiated at admission of the patient. It was used to record the clinical pathway and patient outcomes until the point of discharge or death. Data for 138 patients were collected. 48% of patients commenced NIV within 3 hours with no reduction in door-to-mask time during the study period. Delays in starting NIV were due to: time taken for review by the medical team (101 minutes) and time taken for NIV to be started once a decision had been made (49 minutes). There were significant differences in door-to-NIV decision and mask times between differing respiratory on-call systems, p < 0.05). The introduction of the proforma had no effect on door-to-mask times over the study period. Main reasons for delay were related to timely access to medical staff and to NIV equipment; however, a marked variation in practice within these hospitals was been noted, with a 9-5 respiratory on-call system associated with shorter NIV initiation times.

  8. Universal fungal vaccines

    PubMed Central

    Hamad, Mawieh

    2012-01-01

    The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks. PMID:22922769

  9. Fungal diagnostics in pneumonia.

    PubMed

    Lease, Erika D; Alexander, Barbara D

    2011-12-01

    Fungal pneumonia is increasingly common, particularly in highly immunosuppressed patients, such as solid organ or hematopoietic stem cell transplant recipients, and the diagnosis is evolving. Although standard techniques such as microscopy and culture remain the mainstays of diagnosis, relatively recent advances in serological and molecular testing are important additions to the field. This article reviews the laboratory tools used to diagnose fungal respiratory disease.

  10. Fungal infections of the orbit

    PubMed Central

    Mukherjee, Bipasha; Raichura, Nirav Dilip; Alam, Md. Shahid

    2016-01-01

    Fungal infections of the orbit can lead to grave complications. Although the primary site of inoculation of the infective organism is frequently the sinuses, the patients can initially present to the ophthalmologist with ocular signs and symptoms. Due to its varied and nonspecific clinical features, especially in the early stages, patients are frequently misdiagnosed and even treated with steroids which worsen the situation leading to dire consequences. Ophthalmologists should be familiar with the clinical spectrum of disease and the variable presentation of this infection, as early diagnosis and rapid institution of appropriate therapy are crucial elements in the management of this invasive sino-orbital infection. In this review, relevant clinical, microbiological, and imaging findings are discussed along with the current consensus on local and systemic management. We review the recent literature and provide a comprehensive analysis. In the immunocompromised, as well as in healthy patients, a high index of suspicion must be maintained as delay in diagnosis of fungal pathology may lead to disfiguring morbidity or even mortality. Obtaining adequate diagnostic material for pathological and microbiological examination is critical. Newer methods of therapy, particularly oral voriconazole and topical amphotericin B, may be beneficial in selected patients. PMID:27380972

  11. Laboratory diagnosis of invasive mycoses.

    PubMed

    O'Shaughnessy, Elizabeth M; Shea, Yvonne M; Witebsky, Frank G

    2003-03-01

    Rising numbers of immunocompromised patients have led to an ever-increasing population at risk of invasive fungal disease. Much has been achieved in the laboratory diagnosis of these infections, such as advances in blood culture systems, and the development of new biochemical, antigen detection assays, and molecular methodologies. More standardized susceptibility testing guidelines provide for better therapeutic interventions. In an era of economic cutbacks in health care, future challenges include the development of cost-effective and technically simplified systems, which provide early detection and identification of common and emerging fungal pathogens. It will, however, take some time to establish the clinical relevance of these new methodologies in different patient populations.

  12. Lack of belowground mutualisms hinders Pinaceae invasions.

    PubMed

    Nuñez, Martin A; Horton, Thomas R; Simberloff, Daniel

    2009-09-01

    Why particular invasions succeed and others fail is not well understood. The role of soil biota has been proposed as important. However, the role of mutualists has received much less attention than that of pathogens. Here we report that lack of adequate ectomycorrhizal fungi hinders invasion by exotic Pinaceae on Isla Victoria, Argentina, by reducing both the probability of establishment and growth of invading individuals. More than one hundred exotic tree species were introduced to this island ca. 80 years ago, but invasive trees are found in high densities only in areas adjacent to plantations. With a series of greenhouse and field experiments we found lower mycorrhizal colonization levels and few fungal species far from original plantings, and key fungal mutualists are confined to areas near plantations, probably owing to dispersal limitations. Low inoculum levels far from the plantations are retarding the invasion. Our experiments indicate that positive interactions belowground can play a key but underappreciated role in invasion dynamics.

  13. Topographic diversity of fungal and bacterial communities in human skin.

    PubMed

    Findley, Keisha; Oh, Julia; Yang, Joy; Conlan, Sean; Deming, Clayton; Meyer, Jennifer A; Schoenfeld, Deborah; Nomicos, Effie; Park, Morgan; Kong, Heidi H; Segre, Julia A

    2013-06-20

    Traditional culture-based methods have incompletely defined the microbial landscape of common recalcitrant human fungal skin diseases, including athlete's foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms and provides a home for diverse commensal microbiota. Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders. However, microbial diversity is not limited to bacteria; microorganisms such as fungi also have major roles in microbial community stability, human health and disease. Genomic methodologies to identify fungal species and communities have been limited compared with those that are available for bacteria. Fungal evolution can be reconstructed with phylogenetic markers, including ribosomal RNA gene regions and other highly conserved genes. Here we sequenced and analysed fungal communities of 14 skin sites in 10 healthy adults. Eleven core-body and arm sites were dominated by fungi of the genus Malassezia, with only species-level classifications revealing fungal-community composition differences between sites. By contrast, three foot sites--plantar heel, toenail and toe web--showed high fungal diversity. Concurrent analysis of bacterial and fungal communities demonstrated that physiologic attributes and topography of skin differentially shape these two microbial communities. These results provide a framework for future investigation of the contribution of interactions between pathogenic and commensal fungal and bacterial communities to the maintainenace of human health and to disease pathogenesis.

  14. Evaluation of Human Body Fluids for the Diagnosis of Fungal Infections

    PubMed Central

    2013-01-01

    Invasive fungal infections are a major cause of morbidity and mortality in immunocompromised patients. Because the etiologic agents of these infections are abundant in nature, their isolation from biopsy material or sterile body fluids is needed to document infection. This review evaluates and discusses different human body fluids used to diagnose fungal infections. PMID:23984401

  15. Fungal Genomics Program

    SciTech Connect

    Grigoriev, Igor

    2012-03-12

    The JGI Fungal Genomics Program aims to scale up sequencing and analysis of fungal genomes to explore the diversity of fungi important for energy and the environment, and to promote functional studies on a system level. Combining new sequencing technologies and comparative genomics tools, JGI is now leading the world in fungal genome sequencing and analysis. Over 120 sequenced fungal genomes with analytical tools are available via MycoCosm (www.jgi.doe.gov/fungi), a web-portal for fungal biologists. Our model of interacting with user communities, unique among other sequencing centers, helps organize these communities, improves genome annotation and analysis work, and facilitates new larger-scale genomic projects. This resulted in 20 high-profile papers published in 2011 alone and contributing to the Genomics Encyclopedia of Fungi, which targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts). Our next grand challenges include larger scale exploration of fungal diversity (1000 fungal genomes), developing molecular tools for DOE-relevant model organisms, and analysis of complex systems and metagenomes.

  16. Acute Aspergillus pneumonia associated with mouldy tree bark-chippings, complicated by anti-glomerular basement membrane disease causing permanent renal failure☆

    PubMed Central

    Butler, Louise; Brockley, Tomos; Denning, David; Richardson, Malcolm; Chisholm, Roger; Sinha, Smeeta; O’Driscoll, Ronan

    2013-01-01

    A non-immunocompromised man developed acute Aspergillus pneumonia after spreading mouldy tree bark mulch. Despite normal renal function at presentation, he developed rapidly progressive glomerulonephritis with acute kidney injury due to anti-glomerular basement membrane antibodies (anti-GBM) 4 weeks later. He remained dialysis dependent and died of sepsis 10 months later. We hypothesise that he contracted invasive pulmonary Aspergillosis from heavy exposure to fungal spores, leading to epitope exposure in the alveoli with subsequent development of GBM auto-antibodies. PMID:24432235

  17. Ectomycorrhizal fungal communities coinvading with Pinaceae host plants in Argentina: Gringos bajo el bosque.

    PubMed

    Hayward, Jeremy; Horton, Thomas R; Nuñez, Martin A

    2015-10-01

    Coinvasive ectomycorrhizal (ECM) fungi allow Pinaceae species to invade regions otherwise lacking compatible symbionts, but ECM fungal communities permitting Pinaceae invasions are poorly understood. In the context of Pinaceae invasions on Isla Victoria, Nahuel Huapi National Park, Argentina, we asked: what ECM fungi are coinvading with Pinaceae hosts on Isla Victoria; are some ECM fungal species or genera more prone to invade than others; and are all ECM fungal species that associate with Northern Hemisphere hosts also nonnative, or are some native fungi compatible with nonnative plants? We sampled ECMs from 226 Pinaceae host plant individuals, both planted individuals and recruits, growing inside and invading from plantations. We used molecular techniques to examine ECM fungal communities associating with these trees. A distinctive subset of the ECM fungal community predominated far from plantations, indicating differences between highly invasive and less invasive ECM fungi. Some fungal invaders reported here have been detected in other locations around the world, suggesting strong invasion potential. Fungi that were frequently detected far from plantations are often found in early-successional sites in the native range, while fungi identified as late-successional species in the native range are rarely found far from plantations, suggesting a means for predicting potential fungal coinvaders.

  18. Investigating Invasives

    ERIC Educational Resources Information Center

    Lightbody, Mary

    2008-01-01

    Invasive species, commonly known as "invasives," are nonnative plants, animals, and microbes that completely take over and change an established ecosystem. The consequences of invasives' spread are significant. In fact, many of the species that appear on the Endangered Species list are threatened by invasives. Therefore, the topic of invasive…

  19. Randomized comparison of ticagrelor versus prasugrel in patients with acute coronary syndrome and planned invasive strategy--design and rationale of the iNtracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 trial.

    PubMed

    Schulz, Stefanie; Angiolillo, Dominick J; Antoniucci, David; Bernlochner, Isabell; Hamm, Christian; Jaitner, Juliane; Laugwitz, Karl-Ludwig; Mayer, Katharina; von Merzljak, Barbara; Morath, Tanja; Neumann, Franz-Josef; Richardt, Gert; Ruf, Judith; Schömig, Gisela; Schühlen, Helmut; Schunkert, Heribert; Kastrati, Adnan

    2014-02-01

    In acute coronary syndromes (ACS), a dual antiplatelet regimen with an adenosine diphosphate (ADP) receptor antagonist plus aspirin has become the cornerstone of treatment. The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater, more rapid and consistent platelet inhibition compared to their predecessor clopidogrel. Based on their advantages over clopidogrel in two landmark studies, both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation. Due to differences in ACS populations and conditions investigated, the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy cannot be reliably estimated from independent trials. To date, no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists. The aim of this multicenter, randomized, open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy.

  20. Fungal association with sessile marine invertebrates

    PubMed Central

    Yarden, Oded

    2014-01-01

    The presence and association of fungi with sessile marine animals such as coral and sponges has been well established, yet information on the extent of diversity of the associated fungi is still in its infancy. Culture – as well as metagenomic – and transcriptomic-based analyses have shown that fungal presence in association with these animals can be dynamic and can include “core” residents as well as shifts in fungal communities. Evidence for detrimental and beneficial interactions between fungi and their marine hosts is accumulating and current challenges include the elucidation of the chemical and cellular crosstalk between fungi and their associates within the holobionts. The ecological function of fungi in association with sessile marine animals is complex and is founded on a combination of factors such as fungal origin, host health, environmental conditions and the presence of other resident or invasive microorganisms in the host. Based on evidence from the much more studied terrestrial systems, the evaluation of marine animal–fungal symbioses under varying environmental conditions may well prove to be critical in predicting ecosystem response to global change, including effects on the health of sessile marine animals. PMID:24860565

  1. Burden of serious fungal infections in Ukraine.

    PubMed

    Osmanov, Ali; Denning, David W

    2015-10-01

    Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually.

  2. Granuloma, fungal (Majocchi's) (image)

    MedlinePlus

    This is a picture of a fungal granuloma, a large, red (erythematous) patch (plaque) with a prominent border. Within the borders of the lesion are scattered blisters (pustules) that indicate deeper ...

  3. JGI Fungal Genomics Program

    SciTech Connect

    Grigoriev, Igor V.

    2011-03-14

    Genomes of energy and environment fungi are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). Its key project, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts, pathogens, and biocontrol agents) and biorefinery processes (cellulose degradation, sugar fermentation, industrial hosts), and explores fungal diversity by means of genome sequencing and analysis. Over 50 fungal genomes have been sequenced by JGI to date and released through MycoCosm (www.jgi.doe.gov/fungi), a fungal web-portal, which integrates sequence and functional data with genome analysis tools for user community. Sequence analysis supported by functional genomics leads to developing parts list for complex systems ranging from ecosystems of biofuel crops to biorefineries. Recent examples of such 'parts' suggested by comparative genomics and functional analysis in these areas are presented here

  4. [Invasive yeast infections in neutropenic patients].

    PubMed

    Ruiz Camps, Isabel; Jarque, Isidro

    2016-01-01

    Invasive fungal diseases caused by yeasts still play an important role in the morbidity and mortality in neutropenic patients with haematological malignancies. Although the overall incidence of invasive candidiasis has decreased due to widespread use of antifungal prophylaxis, the incidence of non-Candida albicans Candida species is increasing compared with that of C.albicans, and mortality of invasive candidiasis continues to be high. In addition, there has been an increase in invasive infections caused by an array of uncommon yeasts, including species of the genus Malassezia, Rhodotorula, Trichosporon and Saprochaete, characterised by their resistance to echinocandins and poor prognosis.

  5. Overview of Vertebrate Animal Models of Fungal Infection

    PubMed Central

    Hohl, Tobias M.

    2014-01-01

    Fungi represent emerging infectious threats to human populations worldwide. Mice and other laboratory animals have proved invaluable in modeling clinical syndromes associated with superficial and life-threatening invasive mycoses. This review outlines salient features of common vertebrate animal model systems to study fungal pathogenesis, host antifungal immune responses, and antifungal compounds. PMID:24709390

  6. Metabolism in Fungal Pathogenesis

    PubMed Central

    Ene, Iuliana V.; Brunke, Sascha; Brown, Alistair J.P.; Hube, Bernhard

    2014-01-01

    Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host–fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies. PMID:25190251

  7. Serum Amyloid P Component and Systemic Fungal Infection: Does It Protect the Host or Is It a Trojan Horse?

    PubMed Central

    Klotz, Stephen A.; Sobonya, Richard E.; Lipke, Peter N.; Garcia-Sherman, Melissa C.

    2016-01-01

    It is a striking observation that tissue of patients invaded by the deep mycoses often lacks evidence of an inflammatory response. This lack of host response is often attributed to neutropenia secondary to chemotherapy. However, systematic studies do not support this simplistic explanation. However, invasive fungal lesions are characterized by abundant fungal functional amyloid, which in turn is bound by serum amyloid P component (SAP). We postulate that SAP is important in the local immune response in invasive fungal infections. The interaction between fungal functional amyloid, SAP, and the immune response in deep mycoses is discussed. PMID:27704020

  8. Striking a balance: fungal commensalism versus pathogenesis.

    PubMed

    Iliev, Iliyan D; Underhill, David M

    2013-06-01

    The environment is suffused with nearly countless types of fungi, and our immune systems must be tuned to cope with constant exposure to them. In addition, it is becoming increasingly clear that many surfaces of our bodies are colonized with complex populations of fungi (the mycobiome) in the same way that they are colonized with complex populations of bacteria. The immune system must tolerate colonization with commensal fungi but defend against fungal invasion. Truly life-threatening fungal infections are common only when this balance is disrupted through, for example, profound immunosuppression or genetic mutation. Recent studies have begun to shed light on how this balance is established and maintained, and suggest future studies on the role of fungi in homeostatic conditions.

  9. Invasive Species

    EPA Pesticide Factsheets

    Invasive species have significantly changed the Great Lakes ecosystem. An invasive species is a plant or animal that is not native to an ecosystem, and whose introduction is likely to cause economic, human health, or environmental damage.

  10. Invasive Candidiasis

    MedlinePlus

    ... Invasive candidiasis is an infection caused by a yeast (a type of fungus) called Candida . Unlike Candida ... mouth and throat (also called “thrush”) or vaginal “yeast infections,” invasive candidiasis is a serious infection that ...

  11. Clinical considerations in the early treatment of invasive mould infections and disease.

    PubMed

    Mercier, Toine; Maertens, Johan

    2017-03-01

    Different therapeutic strategies for invasive fungal diseases have been explored, each with particular strengths and weaknesses. Broad-spectrum antifungal prophylaxis seems logical, but selective use is important due to its substantial disadvantages, including interference with diagnostic assays, selection for resistance, drug toxicity and drug-drug interactions. Antimould prophylaxis should be restricted to high-risk groups, such as patients undergoing intensive chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome, allogeneic HSCT patients with prior invasive fungal infection, graft-versus-host-disease or extended neutropenia, recipients of a solid organ transplant, or patients with a high-risk inherited immunodeficiency. An empirical approach, whereby mould-active therapy is started in neutropenic patients with fever unresponsive to broad-spectrum antibiotics, is widely applied but incurs the clinical and cost penalties associated with overtreatment. A benefit for all-cause mortality using empirical therapy has not been shown, but it is recommended for high-risk patients who remain febrile after 4-7 days of broad-spectrum antibiotics and in whom extended neutropenia is anticipated. There is growing interest in delaying antifungal treatment until an invasive fungal infection is confirmed ('pre-emptive' or 'diagnostics-driven' management), prompted by the development of more sensitive diagnostic techniques. Comparisons of empirical versus pre-emptive regimens are sparse, particularly with modern triazole agents, but treatment costs are lower with pre-emptive therapy and the available evidence has not indicated reduced efficacy. Pre-emptive treatment may be appropriate in neutropenic patients who remain febrile after administration of broad-spectrum antibiotics but who are clinically stable. Further work is required to define accurately the specific patient subgroups in which each management approach is optimal.

  12. The impact of increased age on outcome from a strategy of early invasive management and revascularisation in patients with acute coronary syndromes: retrospective analysis study from the ACACIA registry

    PubMed Central

    Prakash, Roshan; Chew, Derek P

    2012-01-01

    Objective To evaluate the impact of increased age on outcome from a strategy of early invasive management and revascularisation in patients with acute coronary syndromes (ACS). Design Retrospective analysis of a national Acute Coronary Syndrome registry (ACACIA). Setting Multiple Australian (n=39) centres; 25% rural, 52% with onsite cardiac surgery. Patients Unselected consecutive patients admitted with confirmed ACS, total n=2559, median 99 per centre. Interventions Management was at the discretion of the treating physician. Analysis of outcome based on age >75 years was compared using Cox proportional hazard with a propensity model to adjust for baseline covariates. Main outcome measures Primary outcome was all-cause mortality. Secondary outcomes were bleeding and a composite of any vascular event or unplanned readmission. Results Elderly patients were more likely to present with high-risk features yet were less likely to receive evidence-based medical therapies or receive diagnostic coronary angiography (75% vs 49%, p<0.0001) and early revascularisation (50% vs 30%, p<0.0001). Multivariate analysis found early revascularisation in the elderly cohort to be associated with lower 12-month mortality hazard (0.4 (0.2–0.7)) and composite outcome (0.6 (0.5–0.8)). Propensity model suggested a greater absolute benefit in elderly patients compared to others. Conclusions Following presentation with ACS, elderly patients are less likely to receive evidence-based medical therapies, to be considered for an early invasive strategy and be revascularised. Increasing age is a significant barrier to physicians when considering early revascularisation. An early invasive strategy with revascularisation when performed was associated with substantial benefit and the absolute accrued benefit appears to be higher in elderly patients. PMID:22344538

  13. Serious fungal infections in the Philippines.

    PubMed

    Batac, M C R; Denning, D

    2017-02-21

    The Philippines is a low middle-income, tropical country in Southeast Asia. Infectious diseases remain the main causes of morbidity, including tuberculosis. AIDS/HIV prevalence is still low at <1%, but is rapidly increasing. Fungal disease surveillance has not been done, and its burden has never been estimated. This becomes more important as the population of immunocompromised patients increases, drawn from patients with AIDS, TB, malignancies, and autoimmune diseases requiring chronic steroid use. Using the methodology of the LIFE program ( www.LIFE-worldwide.org ), estimates were derived from data gathered from WHO, UNAIDS, Philippine Health Statistics 2011, Philippine Dermatological Society Health Information System database, HIV/AIDS and ART registry of the Philippines, epidemiological studies such as The TREAT Asia HIV Observational Database 2005, and personal communication. Aspergillosis and candidiasis were the top causes of fungal infections in the Philippines. Chronic pulmonary aspergillosis (CPA), drawn from the number of tuberculosis patients, affects 77,172 people. Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) frequencies, which were derived from the number of asthmatic patients, affect 121,113 and 159,869 respectively. Recurrent vulvovaginal candidiasis (RVVC) affects 1,481,899 women. Other estimates were cryptococcal meningitis 84, Pneumocystis pneumonia 391, oral candidiasis 3,467, esophageal candidiasis 1,522 (all in HIV-infected people), invasive aspergillosis (IA) 3,085, candidemia 1,968, candida peritonitis 246, mucormycosis 20, fungal keratitis 358, tinea capitis 846 and mycetoma 97 annually. A total of 1,852,137 (1.9% of population) are afflicted with a serious fungal infection. Epidemiological studies are needed to validate these estimates, facilitating appropriate medical care of patients and proper prioritization of limited resources.

  14. A hematology consensus agreement on antifungal strategies for neutropenic patients with hematological malignancies and stem cell transplant recipients. Gruppo Italiano Malattie Ematologiche dell'Adulto, Gruppo Italiano Trapianto di Midollo Osseo, Associazione Italiana Ematologia ed Oncologia Pediatrica, Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and Sorveglianza Epidemiologica delle Infezioni Fungine nelle Emopatie Maligne.

    PubMed

    Girmenia, Corrado; Aversa, Franco; Busca, Alessandro; Candoni, Anna; Cesaro, Simone; Luppi, Mario; Pagano, Livio; Rossi, Giuseppe; Venditti, Adriano; Nosari, Anna Maria

    2013-09-01

    In the attempt to establish key therapy definitions and provide shared approaches to invasive fungal diseases in neutropenic patients, trials of empiric, preeemptive and targeted antifungal therapy (EAT, PAT and TAT) were reviewed, and a Consensus Development Conference Project was convened. The Expert-Panel concurred that all antifungal treatments, including EAT, should always follow an adequate diagnostic strategy and that the standard definition of PAT may be misleading: being PAT guided by the results of a diagnostic work-up, it should better be termed diagnostic-driven antifungal therapy (DDAT). The Expert-Panel agreed that radiological findings alone are insufficient for the choice of a TAT and that the identification of the etiologic pathogen is needed. The Consensus Agreement proceeded identifying which clinical and microbiological findings were sufficient to start a DDAT and which were not. Finally, an algorithm to rationalize the choice of antifungal drugs on the basis of clinical manifestations, antifungal prophylaxis, instrumental and laboratory findings was drawn up.

  15. Eradication of superficial fungal infections by conventional and novel approaches: a comprehensive review.

    PubMed

    Kumar, Lalit; Verma, Shivani; Bhardwaj, Ankur; Vaidya, Shubha; Vaidya, Bhuvaneshwar

    2014-02-01

    During the last two decades, the occurrence of fungal infections either superficial or systemic has been increasing. Moreover, fungal infections become more difficult to treat when they show coupling with immunogenic diseases like AIDS. Superficial fungal infections are associated with skin, nail and eye and are less prominent to systemic infection. However, it may be dangerous if not treated properly. It is usually observed that conventional formulations including cream, powder, gels etc. are used to treat skin fungal infections even for the deep seated fungal infections. However, these formulations show various side-effects on the application site like burning, redness and swelling. Further, due to the immediate release of drug from these formulations they can stimulate the immune system of body generating high impact allergic reactions. Deep seated fungal infections like invasive aspergillosis and invasive candidiasis may be more difficult to treat because the drug released from conventional topical formulation can not reach at the target site due to the low penetration capacity. Similarly, in case of fungal infection of nail and eye, conventional formulations show problem of less bioavailability. Thus, to overcome the drawbacks of conventional therapy a lot of research works have been carried out to develop novel formulations of antifungal drugs to deliver them superficially. Novel formulations explored for the skin delivery of antifungal drugs include liposomes, niosomes, ethosomes, microemulsions, nanoparticles, microspheres and micelles. These formulations show extended or sustained release of drug, minimizing the side effect on application site, enhancing bioavailability and reducing the dosing frequency. Further, these formulations also show penetration into the deep skin to treat invasive fungal infections. Novel formulations explored in treatment of fungal infections of eye are liposomes and nanoparticles and whether for nail fungal infections

  16. Burden of serious fungal infections in the Czech Republic.

    PubMed

    Chrdle, Aleš; Mallátová, Nad'a; Vašáková, Martina; Haber, Jan; Denning, David W

    2015-10-01

    We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care.

  17. The burden of serious human fungal infections in Brazil.

    PubMed

    Giacomazzi, Juliana; Baethgen, Ludmila; Carneiro, Lilian C; Millington, Maria Adelaide; Denning, David W; Colombo, Arnaldo L; Pasqualotto, Alessandro C

    2016-03-01

    In Brazil, human fungal infections are prevalent, however, these conditions are not officially reportable diseases. To estimate the burden of serious fungal diseases in 1 year in Brazil, based on available data and published literature. Historical official data from fungal diseases were collected from Brazilian Unified Health System Informatics Department (DATASUS). For fungal diseases for which no official data were available, assumptions of frequencies were made by estimating based on published literature. The incidence (/1000) of hospital admissions for coccidioidomycosis was 7.12; for histoplasmosis, 2.19; and for paracoccidioidomycosis, 7.99. The estimated number of cryptococcal meningoencephalitis cases was 6832. Also, there were 4115 cases of Pneumocystis pneumonia in AIDS patients per year, 1 010 465 aspergillosis and 2 981 416 cases of serious Candida infections, including invasive and non-invasive diseases. In this study, we demonstrate that more than 3.8 million individuals in Brazil may be suffering from serious fungal infections, mostly patients with malignant cancers, transplant recipients, asthma, previous tuberculosis, HIV infection and those living in endemic areas for truly pathogenic fungi. The scientific community and the governmental agencies should work in close collaboration in order to reduce the burden of such complex, difficult-to-diagnose and hard to treat diseases.

  18. Invasive mucormycosis in chronic granulomatous disease

    PubMed Central

    Al-Otaibi, Abdulnasir M.; Al-Shahrani, Dayel A.; Al-Idrissi, Eman M.; Al-Abdely, Hail M.

    2016-01-01

    Mucormycosis is a rare opportunistic fungal infection that occurs in certain immunocompromised patients. We present 2 cases of invasive mucormycosis due to Rhizopus spp. in patients with chronic granulomatous disease (CGD) and discuss their clinical presentation, management challenges, and outcomes. PMID:27146621

  19. Aspergillus niger: an unusual cause of invasive pulmonary aspergillosis

    PubMed Central

    Person, A. K.; Chudgar, S. M.; Norton, B. L.; Tong, B. C.; Stout, J. E.

    2010-01-01

    Infections due to Aspergillus species cause significant morbidity and mortality. Most are attributed to Aspergillus fumigatus, followed by Aspergillus flavus and Aspergillus terreus. Aspergillus niger is a mould that is rarely reported as a cause of pneumonia. A 72-year-old female with chronic obstructive pulmonary disease and temporal arteritis being treated with steroids long term presented with haemoptysis and pleuritic chest pain. Chest radiography revealed areas of heterogeneous consolidation with cavitation in the right upper lobe of the lung. Induced bacterial sputum cultures, and acid-fast smears and cultures were negative. Fungal sputum cultures grew A. niger. The patient clinically improved on a combination therapy of empiric antibacterials and voriconazole, followed by voriconazole monotherapy. After 4 weeks of voriconazole therapy, however, repeat chest computed tomography scanning showed a significant progression of the infection and near-complete necrosis of the right upper lobe of the lung. Serum voriconazole levels were low–normal (1.0 μg ml−1, normal range for the assay 0.5–6.0 μg ml−1). A. niger was again recovered from bronchoalveolar lavage specimens. A right upper lobectomy was performed, and lung tissue cultures grew A. niger. Furthermore, the lung histopathology showed acute and organizing pneumonia, fungal hyphae and oxalate crystallosis, confirming the diagnosis of invasive A. niger infection. A. niger, unlike A. fumigatus and A. flavus, is less commonly considered a cause of invasive aspergillosis (IA). The finding of calcium oxalate crystals in histopathology specimens is classic for A. niger infection and can be helpful in making a diagnosis even in the absence of conidia. Therapeutic drug monitoring may be useful in optimizing the treatment of IA given the wide variations in the oral bioavailability of voriconazole. PMID:20299503

  20. Invasive pulmonary aspergillosis in neutropenic patients and the influence of hospital renovation.

    PubMed

    Pini, Gabriella; Faggi, Elisabetta; Donato, Rosa; Sacco, Cristiana; Fanci, Rosa

    2008-03-01

    To evaluate the effects of airborne Aspergillus contamination during and after the renovation work of a Florentine haematology unit, we conducted (November 2003-January 2005) a strict programme of environmental fungal surveillance. Air samples were taken from patients' rooms, along the corridors inside the wards, along the corridor between wards and outside the building. The concentration of Aspergillus fumigatus was high along the corridor between the two haematology wards (2.98 CFU m(-3)), lower in the non-neutropenic patients' rooms and outside the hospital building (1.53 and 1.42 CFU m(-3), respectively), very low in the neutropenic patients' rooms (0.09 CFU m(-3)). During this period, three proven cases (A. fumigatus), two probable ones and two possible cases of invasive pulmonary aspergillosis were documented in 97 patients with acute leukaemia (7%). The three cases of proven aspergillosis coincided with the period of renovation work and with the period in which we have found the maximum concentration of A. fumigatus along the corridor. These data suggest a possible relationship between environmental fungal contamination and the incidence of invasive aspergillosis, and underline the importance of environmental surveillance.

  1. Fungal rhinitis in dogs.

    PubMed

    Ostrzeszewicz, M; Sapierzyński, R

    2015-01-01

    Fungal rhinitis and sinusitis in dogs are quite common reasons of chronic nasal discharge and rhinoscopy in such cases is commonly suggested. Forty three dogs were examined using rhinoscopy because of the presence of chronic airway symptoms. Clinical examination, routine hematology and serum biochemistry profiles, nasal and frontal sinus radiographs were made in all animals. Additionally, computed tomography in one dog was performed. Samples for histopathology were taken from 9 patients during rhinoscopy, additionally, from 8 of these patients samples for cytopathology were collected by blind nasal swab technique. In 9 of 43 dogs (20,5%), all males aged 1 to 13 years, examinations led to a diagnosis of fungal rhinitis. In 2 cases a diagnosis of fungal rhinitis was obtained based solely on cytopathology, while in 7 cases - mycosis of nasal mucosa was confirmed by histopathology. The present study revealed that cytopathological examination of nasal swabs has a low diagnostic value in the case of nasal infections in dogs. Although, in some dogs cytopathology, together with other widely available diagnostic techniques was sufficient to reliably diagnose fungal rhinitis, histopathology of samples collected during rhinoscopy is still the gold standard in such cases.

  2. Immunoregulation in Fungal Diseases

    PubMed Central

    Roussey, Jonathan A.; Olszewski, Michal A.; Osterholzer, John J.

    2016-01-01

    This review addresses specific regulatory mechanisms involved in the host immune response to fungal organisms. We focus on key cells and regulatory pathways involved in these responses, including a brief overview of their broader function preceding a discussion of their specific relevance to fungal disease. Important cell types discussed include dendritic cells and regulatory T cells, with a focus on specific studies relating to their effects on immune responses to fungi. We highlight the interleukin-10, programmed cell death 1, and cytotoxic T lymphocyte-associated protein 4 signaling pathways and emphasize interrelationships between these pathways and the regulatory functions of dendritic cells and regulatory T cells. Throughout our discussion, we identify selected studies best illustrating the role of these cells and pathways in response to specific fungal pathogens to provide a contextual understanding of the tightly-controlled network of regulatory mechanisms critical to determining the outcome of exposure to fungal pathogens. Lastly, we discuss two unique phenomena relating to immunoregulation, protective tolerance and immune reactivation inflammatory syndrome. These two clinically-relevant conditions provide perspective as to the range of immunoregulatory mechanisms active in response to fungi. PMID:27973396

  3. Fungal Burn Wound Infection

    DTIC Science & Technology

    1991-01-01

    severely limits the may prove to be useful in burn patients. Clotrimazole , applied clinical utility of such a culture. Biopsy and frozen-section and as...useful in wound and permit prompt institution of appropriate the treatment of systemic fungal infections. Clotrimazole is treatment. poorly absorbed

  4. Sputum fungal smear

    MedlinePlus

    ... A.D.A.M. Editorial team. Related MedlinePlus Health Topics Fungal Infections Lung Diseases Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare ... for online health information and services. Learn more about A.D. ...

  5. Who Gets Fungal Infections?

    MedlinePlus

    ... infections can also happen in people without weak immune systems Fungal infections that are not life-threatening, such ... likely to cause an infection. People with weak immune systems Infections that happen because a person’s immune system ...

  6. Nail Fungal Infections

    MedlinePlus

    ... Are treatments usually effective?Are there any side effects of the treatment?If my treatment works, will my nail grow back normally?If I've had one fungal nail infection, am I likely to get another?What kinds of shoes should I wear?Should I wear gloves when ...

  7. Advances and challenges in management of invasive mycoses.

    PubMed

    Patterson, Thomas F

    Invasive mycoses pose a major diagnostic and therapeutic challenge. Advances in antifungal agents and diagnostic methods offer the potential for improved outcomes in patients with these infections, which are often lethal. Many fungal pathogens occur almost exclusively in opportunistic settings--in the immunocompromised host--and these infections are the focus of this review. Several areas of ongoing challenge remain, including the emergence of resistant organisms and the absence of reliable markers for early identification of patients at risk of developing invasive fungal disease. This Seminar reviews the changing epidemiology of invasive mycoses, new diagnostic methods, and recent therapeutic options and current management strategies for these opportunistic pathogens.

  8. A combination approach to treating fungal infections

    PubMed Central

    Shrestha, Sanjib K.; Fosso, Marina Y.; Garneau-Tsodikova, Sylvie

    2015-01-01

    Azoles are antifungal drugs used to treat fungal infections such as candidiasis in humans. Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, C12 and C14, were shown to display antifungal activities. Herein, the antifungal synergy of C12 and C14 with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS), and voriconazole (VOR), was examined against seven Candida albicans strains. All tested strains were synergistically inhibited by C12 when combined with azoles, with the exception of C. albicans 64124 and MYA-2876 by FLC and VOR. Likewise, when combined with POS and ITC, C14 exhibited synergistic growth inhibition of all C. albicans strains, except C. albicans MYA-2876 by ITC. The combinations of FLC-C14 and VOR-C14 showed synergistic antifungal effect against three C. albicans and four C. albicans strains, respectively. Finally, synergism between C12/C14 and POS were confirmed by time-kill and disk diffusion assays. These results suggest the possibility of combining C12 or C14 with azoles to treat invasive fungal infections at lower administration doses or with a higher efficiency. PMID:26594050

  9. Fungal osteomyelitis of maxillofacial bones: Rare presentation

    PubMed Central

    Urs, Aadithya B; Singh, Hanspal; Mohanty, Sujata; Sharma, Pankaj

    2016-01-01

    Osteomyelitis is defined as inflammation of the medullary cavities, haversian system and adjacent cortex of bone. Osteomyelitis involving maxilla is quite rare when compared to that of mandible. Fungal osteomyelitis is very rarely seen and documented in the maxillofacial area. It is devastating to patients if it is invasive in nature. A prospective study was undertaken from December 2011 to December 2013. Biopsied hard tissue bits were decalcified and sections were stained with H&E, periodic acid Schiff and Grocott methenamine silver. Culture sensitivity was carried out in all cases. Surgical intervention followed by antifungal therapy was advocated to treat the patients. The current series showed five cases of fungal osteomyelitis which included candidal osteomyelitis, aspergillosis and mucormycosis with slight predominance of maxilla over mandible. Osteomyelitis of facial bones needs to be investigated thoroughly as there is no difference in clinical presentation between bacterial and fungal osteomyelitis. The diagnostic workup with biopsy and culture sensitivity helps to identify the pathogen at the earliest. Appropriate antifungal treatment needs to be advocated for successful treatment. PMID:27721629

  10. Reintroduction of locally extinct vertebrates impacts arid soil fungal communities.

    PubMed

    Clarke, Laurence J; Weyrich, Laura S; Cooper, Alan

    2015-06-01

    Introduced species have contributed to extinction of native vertebrates in many parts of the world. Changes to vertebrate assemblages are also likely to alter microbial communities through coextinction of some taxa and the introduction of others. Many attempts to restore degraded habitats involve removal of exotic vertebrates (livestock and feral animals) and reintroduction of locally extinct species, but the impact of such reintroductions on microbial communities is largely unknown. We used high-throughput DNA sequencing of the fungal internal transcribed spacer I (ITS1) region to examine whether replacing exotic vertebrates with reintroduced native vertebrates led to changes in soil fungal communities at a reserve in arid central Australia. Soil fungal diversity was significantly different between dune and swale (interdune) habitats. Fungal communities also differed significantly between sites with exotic or reintroduced native vertebrates after controlling for the effect of habitat. Several fungal operational taxonomic units (OTUs) found exclusively inside the reserve were present in scats from reintroduced native vertebrates, providing a direct link between the vertebrate assemblage and soil microbial communities. Our results show that changes to vertebrate assemblages through local extinctions and the invasion of exotic species can alter soil fungal communities. If local extinction of one or several species results in the coextinction of microbial taxa, the full complement of ecological interactions may never be restored.

  11. Occurrence of Fungal DNA Contamination in PCR Reagents: Approaches to Control and Decontamination.

    PubMed

    Czurda, S; Smelik, S; Preuner-Stix, S; Nogueira, F; Lion, T

    2016-01-01

    Nucleic acid amplification techniques permitting sensitive and rapid screening in patients at risk for invasive fungal infections are an important addition to conventional fungal diagnostic methods. However, contamination with fungal DNA may be a serious threat to the validity of fungal amplification-based assays. Besides rigorous handling procedures to avoid false-positive test results from exogenous sources, we have implemented protocols for comprehensive assessment of fungal contamination in all materials involved in the analytical process. Traces of fungal DNA were found in different commercially available PCR reagents, including lyophilized primers, TaqMan probes, and master mix solutions. These contaminants resulted in a considerable rate of false-positive tests in panfungal real-time PCR analysis. To address this problem, we have established a decontamination protocol based on the activity of a double-strand specific DNase. Using this approach, we have significantly reduced the frequency of false-positive test results attributable to contaminated reagents. On the basis of our findings, we strongly recommend routine monitoring of all reagents used in fungal PCR assays for the presence of relevant contaminants. As long as fungal-grade reagents are not readily available, pretreatment methods facilitating elimination of fungal DNA are critical for reducing the risk of false-positive results in highly sensitive molecular fungal detection assays.

  12. Acute graft-versus-host disease, invasive aspergillosis and Clostridium difficile colitis after peripheral blood stem cell transplantation: A complex network of causalities and a challenge for prevention.

    PubMed

    Khanafer, Nagham; Neuraz, Antoine; Bénet, Thomas; Cour, Martin; Persat, Florence; Labussière, Hélène; Argaud, Laurent; Michallet, Mauricette; Vanhems, Philippe

    2015-06-01

    Graft-versus-host disease (GVHD) is a known risk factor for invasive aspergillosis (IA), but remains poorly studied in relation to Clostridium difficile infection (CDI). We report a case of a 58-years-old patient who developed an IA within a protected room, CDI and GVHD after allogeneic allogeneic peripheral blood stem cell transplantation (PBSCT). Factors associated with this complex condition in patients receiving allogeneic PBSCT need to be identified.

  13. New insights on the development of fungal vaccines: from immunity to recent challenges

    PubMed Central

    Medici, Natasha P; Del Poeta, Maurizio

    2015-01-01

    Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality. PMID:26602871

  14. New insights on the development of fungal vaccines: from immunity to recent challenges.

    PubMed

    Medici, Natasha P; Del Poeta, Maurizio

    2015-12-01

    Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

  15. Immunology of fungal infections in animals.

    PubMed

    Lehmann, P F

    1985-10-01

    The nature of immunity to fungal infection is discussed predominantly for mammals and birds. T-cell-mediated immunity seems essential for recovery both from cutaneous and mucosal infections (Candida, Malassezia and dermatophytes) and from infections of systemic fungal pathogens (Cryptococcus, Blastomyces, Histoplasma, and Coccidioides). Often chronic progressive disease caused by these fungi is associated with a depression or absence of T-cell-mediated immunity to antigens of the infecting fungus. In contrast recovery from disease, or absence of clinical disease after exposure to these fungi, is associated with the presence of strong T-cell-mediated immune responses to the fungus. The activation of macrophages and the stimulation of epidermal growth and keratinization are the processes induced by T-cell-mediated immunity which result in the resolution of systemic or cutaneous and mucosal disease. Other cell types, for example NK cells and PMNs (polymorphonuclear leucocytes), may be important in these diseases in reducing the effective amount of inoculum to which an animal is exposed and thereby reducing the likelihood of disseminated disease. Invasive opportunistic fungi (Candida, Aspergillus, Mucorales) are resisted by PMNs which attach to the hyphae or pseudohyphae and damage them via an extracellular mechanism. Other host cell types may be important in natural resistance, fungal spores being handled by the macrophages which, under conditions when animals are not immunosuppressed, are likely to be an effective first line of defense. Subcutaneous pathogens and miscellaneous other fungal diseases are discussed from a point of view of host immunity and immunodiagnosis. Vaccine development for ringworm and for other mycoses is discussed.

  16. Burden of serious fungal infections in Bangladesh.

    PubMed

    Gugnani, H C; Denning, D W; Rahim, R; Sadat, A; Belal, M; Mahbub, M S

    2017-02-04

    In Bangladesh there are several published papers on superficial mycoses. Deep mycoses are also recognized as an important emerging problem. Here, we estimate the annual incidence and prevalence of serious fungal infections in Bangladesh. Demographic data were obtained from world population reports and the data on TB and HIV extracted from the online publications on tuberculosis in Bangladesh and Asia Pacific research statistical data information resources AIDS Data HUB. All the published papers on fungal infections in Bangladesh were identified through extensive search of literature. We estimated the number of affected people from populations at risk and local epidemiological data. Bangladesh has a population of ∼162.6 million, 31% children and only 6% over the age of 60 years. The pulmonary TB caseload reported in 2014 was 119,520, and we estimate a prevalence of 30,178 people with chronic pulmonary aspergillosis, 80% attributable to TB. An anticipated 90,262 and 119,146 patients have allergic bronchopulmonary aspergillosis or severe asthma with fungal sensitization. Only 8,000 people are estimated to be HIV-infected, of whom 2900 are not on ART with a CD4 count <350 μL, Pneumocystis pneumonia and cryptococcal meningitis being rare. Superficial mycoses are very common with Trichophyton rubrum as the predominant etiological agent (80.6%). Numerous cases of mycotic keratitis have been reported from several parts of Bangladesh. Candida bloodstream infection was estimated based on a 5 per 100,000 rate (8100 cases) and invasive aspergillosis based primarily on leukemia and COPD rates, at 5166 cases. Histoplasmosis was documented in 16 cases mostly with disseminated disease and presumed in 21 with HIV infection. This study constitutes the first attempt to estimate the burden of several types of serious fungal infections in Bangladesh.

  17. Occult Fungal Scleritis

    PubMed Central

    Jeang, Lauren J.; Davis, Aaron; Madow, Brian; Espana, Edgar M.; Margo, Curtis E.

    2017-01-01

    Purpose To heighten awareness of occult fungal scleritis. Method Case report and review of the literature. Results A 73-year-old woman with diabetes mellitus was diagnosed for 3 months with immune-mediated scleritis and subsequently treated with corticosteroids. On referral, the patient had a scleral nodule with contiguous corneal infiltrate and hypopyon. Culture grew Fusarium species not further classified. The infection could not be controlled with antifungal therapy, and the eye was removed. No exogenous or endogenous source for the infection could be identified by clinical history or examination. Conclusion Fungal scleritis can develop in persons without a history of foreign body injury, minor trauma, or evidence of endogenous fungemia. A high index of suspicion for infectious scleritis must be maintained in persons with presumed immune-mediated scleritis who fail to respond to conventional therapy, particularly if they present with decreased visual acuity. PMID:28275602

  18. Unusual fungal niches.

    PubMed

    Cantrell, S A; Dianese, J C; Fell, J; Gunde-Cimerman, N; Zalar, P

    2011-01-01

    Fungi are found in all aerobic ecosystems, colonizing a diversity of substrates and performing a wide diversity of functions, some of which are not well understood. Many spices of fungi are cosmopolitan and generalists or habitats. Unusual fungal niches are habitats where extreme conditions would be expected to prevent the development of a mycobiota. In this review we describe five unusual fungal habitats in which fungi occupy poorly understood niches: Antarctic dry valleys, high Arctic glaciers, salt flats and salterns, hypersaline microbial mats and plant trichomes. Yeasts, black yeast-like fungi, melanized filamentous species as well as representatives of Aspergillus and Penicillium seem to be dominant among the mycobiota adapted to cold and saline niches. Plant trichomes appear to be a taxa. The advent of new sequencing technologies is helping to elucidate the microbial diversity in many ecosystems, but more studies are needed to document the functional role of fungi in the microbial communities thriving in these unusual environments.

  19. Fungal diseases of horses.

    PubMed

    Cafarchia, Claudia; Figueredo, Luciana A; Otranto, Domenico

    2013-11-29

    Among diseases of horses caused by fungi (=mycoses), dermatophytosis, cryptococcosis and aspergillosis are of particular concern, due their worldwide diffusion and, for some of them, zoonotic potential. Conversely, other mycoses such as subcutaneous (i.e., pythiosis and mycetoma) or deep mycoses (i.e., blastomycosis and coccidioidomycosis) are rare, and/or limited to restricted geographical areas. Generally, subcutaneous and deep mycoses are chronic and progressive diseases; clinical signs include extensive, painful lesions (not pathognomonic), which resemble to other microbial infections. In all cases, early diagnosis is crucial in order to achieve a favorable prognosis. Knowledge of the epidemiology, clinical signs, and diagnosis of fungal diseases is essential for the establishment of effective therapeutic strategies. This article reviews the clinical manifestations, diagnosis and therapeutic protocols of equine fungal infections as a support to early diagnosis and application of targeted therapeutic and control strategies.

  20. Seed bank survival of an invasive species, but not of two native species, declines with invasion.

    PubMed

    Orrock, John L; Christopher, Cory C; Dutra, Humberto P

    2012-04-01

    Soil-borne seed pathogens may play an important role in either hindering or facilitating the spread of invasive exotic plants. We examined whether the invasive shrub Lonicera maackii (Caprifoliaceae) affected fungi-mediated mortality of conspecific and native shrub seeds in a deciduous forest in eastern Missouri. Using a combination of L. maackii removal and fungicide treatments, we found no effect of L. maackii invasion on seed viability of the native Symphoricarpos orbiculatus (Caprifoliaceae) or Cornus drummondii (Cornaceae). In contrast, fungi were significant agents of L. maackii seed mortality in invaded habitats. Losses of L. maackii to soil fungi were also significant in invaded habitats where L. maackii had been removed, although the magnitude of the effect of fungi was lower, suggesting that changes in soil chemistry or microhabitat caused by L. maackii were responsible for affecting fungal seed pathogens. Our work suggests that apparent competition via soil pathogens is not an important factor contributing to impacts of L. maackii on native shrubs. Rather, we found that fungal seed pathogens have density-dependent effects on L. maackii seed survival. Therefore, while fungal pathogens may provide little biotic resistance to early invasion by L. maackii, our study illustrates that more work is needed to understand how changes in fungal pathogens during the course of an invasion contribute to the potential for restoration of invaded systems. More generally, our study suggests that increased rates of fungal pathogen attack may be realized by invasive plants, such as L. maackii, that change the chemical or physical environment of the habitats they invade.

  1. Neonatal invasive candidiasis.

    PubMed

    Stronati, M; Decembrino, L

    2006-12-01

    Over the last two decades, systemic fungal infections have emerged to play a primary role in hospital-acquired infections. C. albicans is involved in 75% of neonatal candidiasis; however, the incidence of infection from C. parapsilosis is also increasing significantly. The higher incidence observed in the high-risk group of very low birth weight (VLBW) infants is linked to their special physical characteristics and the diagnostic and therapeutic invasive procedures they undergo. Colonization is a relevant risk factor depending on the colonized site , the fungal species and the type of colonization. Serological tests have a low specificity and sensitivity; in many cases, they do not distinguish between colonization and infection. Blood culture, although the best diagnostic test for determining systemic infection, can result negative, even in cases of deep organ involvement. In addition, fungi grow more slowly than bacteria in cultures. So, the difficulty in diagnosing systemic candidiasis and its aspecific clinical features may make empirical therapy appropriate. Amphotericin B (AmB) alone or combined with 5-fluorocytosine remains the drug of choice. Fluconazole represents a valid alternative. Recently developed new formulations of amphotericin incapsulated in liposomes can avoid possible adverse effects. Prognosis depends on the specific micro-organism involved; mortality is higher in the presence of C. albicans. As prognosis is associated with high mortality, prevention measures to reduce risk factors are of critical importance.

  2. Fungal CSL transcription factors

    PubMed Central

    Převorovský, Martin; Půta, František; Folk, Petr

    2007-01-01

    Background The CSL (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) transcription factor family members are well-known components of the transmembrane receptor Notch signaling pathway, which plays a critical role in metazoan development. They function as context-dependent activators or repressors of transcription of their responsive genes, the promoters of which harbor the GTG(G/A)GAA consensus elements. Recently, several studies described Notch-independent activities of the CSL proteins. Results We have identified putative CSL genes in several fungal species, showing that this family is not confined to metazoans. We have analyzed their sequence conservation and identified the presence of well-defined domains typical of genuine CSL proteins. Furthermore, we have shown that the candidate fungal protein sequences contain highly conserved regions known to be required for sequence-specific DNA binding in their metazoan counterparts. The phylogenetic analysis of the newly identified fungal CSL proteins revealed the existence of two distinct classes, both of which are present in all the species studied. Conclusion Our findings support the evolutionary origin of the CSL transcription factor family in the last common ancestor of fungi and metazoans. We hypothesize that the ancestral CSL function involved DNA binding and Notch-independent regulation of transcription and that this function may still be shared, to a certain degree, by the present CSL family members from both fungi and metazoans. PMID:17629904

  3. Developments in Fungal Taxonomy

    PubMed Central

    Guarro, Josep; Gené, Josepa; Stchigel, Alberto M.

    1999-01-01

    Fungal infections, especially those caused by opportunistic species, have become substantially more common in recent decades. Numerous species cause human infections, and several new human pathogens are discovered yearly. This situation has created an increasing interest in fungal taxonomy and has led to the development of new methods and approaches to fungal biosystematics which have promoted important practical advances in identification procedures. However, the significance of some data provided by the new approaches is still unclear, and results drawn from such studies may even increase nomenclatural confusion. Analyses of rRNA and rDNA sequences constitute an important complement of the morphological criteria needed to allow clinical fungi to be more easily identified and placed on a single phylogenetic tree. Most of the pathogenic fungi so far described belong to the kingdom Fungi; two belong to the kingdom Chromista. Within the Fungi, they are distributed in three phyla and in 15 orders (Pneumocystidales, Saccharomycetales, Dothideales, Sordariales, Onygenales, Eurotiales, Hypocreales, Ophiostomatales, Microascales, Tremellales, Poriales, Stereales, Agaricales, Schizophyllales, and Ustilaginales). PMID:10398676

  4. Fungal quorum sensing molecules: Role in fungal morphogenesis and pathogenicity.

    PubMed

    Wongsuk, Thanwa; Pumeesat, Potjaman; Luplertlop, Natthanej

    2016-05-01

    When microorganisms live together in high numbers, they need to communicate with each other. To achieve cell-cell communication, microorganisms secrete molecules called quorum-sensing molecules (QSMs) that control their biological activities and behaviors. Fungi secrete QSMs such as farnesol, tyrosol, phenylethanol, and tryptophol. The role of QSMs in fungi has been widely studied in both yeasts and filamentous fungi, for example in Candida albicans, C. dubliniensis, Aspergillus niger, A. nidulans, and Fusarium graminearum. QSMs impact fungal morphogenesis (yeast-to-hypha formation) and also play a role in the germination of macroconidia. QSMs cause fungal cells to initiate programmed cell death, or apoptosis, and play a role in fungal pathogenicity. Several types of QSMs are produced during stages of biofilm development to control cell population or morphology in biofilm communities. This review article emphasizes the role of fungal QSMs, especially in fungal morphogenesis, biofilm formation, and pathogenicity. Information about QSMs may lead to improved measures for controlling fungal infection.

  5. Delivering on Antimicrobial Resistance Agenda Not Possible without Improving Fungal Diagnostic Capabilities

    PubMed Central

    Perlin, David S.; Muldoon, Eavan G.; Colombo, Arnaldo Lopes; Chakrabarti, Arunaloke; Richardson, Malcolm D.; Sorrell, Tania C.

    2017-01-01

    Antimicrobial resistance, a major public health concern, largely arises from excess use of antibiotic and antifungal drugs. Lack of routine diagnostic testing for fungal diseases exacerbates the problem of antimicrobial drug empiricism, both antibiotic and antifungal. In support of this contention, we cite 4 common clinical situations that illustrate this problem: 1) inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis; 2) failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis; 3) misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease; and 4) overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients. All communities should have access to nonculture fungal diagnostics, which can substantially benefit clinical outcome, antimicrobial stewardship, and control of antimicrobial resistance. PMID:27997332

  6. Delivering on Antimicrobial Resistance Agenda Not Possible without Improving Fungal Diagnostic Capabilities.

    PubMed

    Denning, David W; Perlin, David S; Muldoon, Eavan G; Colombo, Arnaldo Lopes; Chakrabarti, Arunaloke; Richardson, Malcolm D; Sorrell, Tania C

    2017-02-01

    Antimicrobial resistance, a major public health concern, largely arises from excess use of antibiotic and antifungal drugs. Lack of routine diagnostic testing for fungal diseases exacerbates the problem of antimicrobial drug empiricism, both antibiotic and antifungal. In support of this contention, we cite 4 common clinical situations that illustrate this problem: 1) inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis; 2) failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis; 3) misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease; and 4) overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients. All communities should have access to nonculture fungal diagnostics, which can substantially benefit clinical outcome, antimicrobial stewardship, and control of antimicrobial resistance.

  7. A fungal growth model fitted to carbon-limited dynamics of Rhizoctonia solani.

    PubMed

    Jeger, M J; Lamour, A; Gilligan, C A; Otten, W

    2008-01-01

    Here, a quasi-steady-state approximation was used to simplify a mathematical model for fungal growth in carbon-limiting systems, and this was fitted to growth dynamics of the soil-borne plant pathogen and saprotroph Rhizoctonia solani. The model identified a criterion for invasion into carbon-limited environments with two characteristics driving fungal growth, namely the carbon decomposition rate and a measure of carbon use efficiency. The dynamics of fungal spread through a population of sites with either low (0.0074 mg) or high (0.016 mg) carbon content were well described by the simplified model with faster colonization for the carbon-rich environment. Rhizoctonia solani responded to a lower carbon availability by increasing the carbon use efficiency and the carbon decomposition rate following colonization. The results are discussed in relation to fungal invasion thresholds in terms of carbon nutrition.

  8. Prevention and treatment of fungal infections in bone marrow transplantation.

    PubMed

    Mossad, Sherif B

    2003-07-01

    There has not been as much success in the prevention and treatment of invasive fungal infections, particularly aspergillosis, compared to the prevention and treatment of cytomegalovirus infection and graft-versus-host disease in bone marrow transplant (BMT) recipients. Allogeneic BMT recipients who develop graft-versus-host disease and remain immunosuppressed for long periods are at major risk for development of these infections. Prevention of environmental exposure, antifungal chemoprophylaxis, and attempts at early diagnosis are essential for the reduction of mortality from invasive fungal infections. Chest computerized axial tomography is extremely useful in diagnosing pulmonary aspergillosis. However, microbiologic or histologic identification of infection remains essential. Unfortunately, the response to therapy in BMT recipients remains suboptimal. With the development of the lipid formulations of amphotericin B, the newer azoles, and the echinocandins, safer and more efficacious options have become available. The optimal use of antifungal agents or their combinations remains to be determined.

  9. Burden of serious fungal diseases in Hungary.

    PubMed

    Sinkó, János; Sulyok, Mihály; Denning, David W

    2015-10-01

    Valid data on the prevalence of serious fungal diseases are difficult to derive as in most countries these conditions are not reportable infections. To assess the burden of these infections in Hungary prevalence estimates from international peer-reviewed papers and population statistics were utilised. In the intensive care unit (ICU) population at least 370 cases of serious yeast and 52 mould infections can be expected yearly. The total number of candidaemia cases may be as high as 1110 annually. In patients with acute leukaemia and recipients of haematopoietic stem cell and solid organ transplants the predicted incidence is more than 55 every year. Recurrent vulvovaginal candidiasis--though not a life-threatening condition--can adversely affect the quality of life of more than 177,000 Hungarian women. According to organisation for economic co-operation and development (OECD), 4.7% of total population older than 15 will suffer from chronic obstructive pulmonary disease (COPD) and 4.4% from asthma, adding another very broad risk group to the aforementioned categories susceptible for mycotic complications. Here more than 17,000 can have severe asthma with fungal sensitisation (SAFS) and more than 13,000 are at risk for developing allergic bronchopulmonary aspergillosis (ABPA). The incidence of dermatomycoses and other superficial fungal infections is even more difficult to assess but--according to international estimations--can affect around 14.3% of the total population. More than 1.6 million Hungarians may suffer from fungal diseases annually, with 33,000 cases being life threatening or very serious. This is an under-recognised problem of special importance for public health.

  10. Bacterial, Fungal, Parasitic, and Viral Myositis

    PubMed Central

    Crum-Cianflone, Nancy F.

    2008-01-01

    Infectious myositis may be caused by a broad range of bacterial, fungal, parasitic, and viral agents. Infectious myositis is overall uncommon given the relative resistance of the musculature to infection. For example, inciting events, including trauma, surgery, or the presence of foreign bodies or devitalized tissue, are often present in cases of bacterial myositis. Bacterial causes are categorized by clinical presentation, anatomic location, and causative organisms into the categories of pyomyositis, psoas abscess, Staphylococcus aureus myositis, group A streptococcal necrotizing myositis, group B streptococcal myositis, clostridial gas gangrene, and nonclostridial myositis. Fungal myositis is rare and usually occurs among immunocompromised hosts. Parasitic myositis is most commonly a result of trichinosis or cystericercosis, but other protozoa or helminths may be involved. A parasitic cause of myositis is suggested by the travel history and presence of eosinophilia. Viruses may cause diffuse muscle involvement with clinical manifestations, such as benign acute myositis (most commonly due to influenza virus), pleurodynia (coxsackievirus B), acute rhabdomyolysis, or an immune-mediated polymyositis. The diagnosis of myositis is suggested by the clinical picture and radiologic imaging, and the etiologic agent is confirmed by microbiologic or serologic testing. Therapy is based on the clinical presentation and the underlying pathogen. PMID:18625683

  11. Giant Fungal Gastric Ulcer in an Immunocompetent Individual

    PubMed Central

    Rai, Praveer; Chakraborty, Sunil B.

    2012-01-01

    Candida infection of gastrointestinal tract is frequent in immunocompromised patients and rare in an otherwise healthy person in whom no permissive factor is present. Herein is a case report on 25-year-old woman, 2 months postpartum, with fungal gastric ulcer with invasion leading to fungemia. She developed fever and anemia. Gastric biopsy and blood culture both showed growth of Candida albicans. The patient responded well to parenteral amphotericin B. This supports the hypothesis of invasion of Candida from gastric ulcer into blood. PMID:22824773

  12. Fungal osteomyelitis and septic arthritis.

    PubMed

    Bariteau, Jason T; Waryasz, Gregory R; McDonnell, Matthew; Fischer, Staci A; Hayda, Roman A; Born, Christopher T

    2014-06-01

    Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in the setting of immunodeficiency and conditions that require immunosuppression. Because fungal osteomyelitis and fungal septic arthritis are rare conditions, study of their pathophysiology and treatment has been limited. In the literature, evidence-based treatment is lacking and, historically, outcomes have been poor. The most common offending organisms are Candida and Aspergillus, which are widely distributed in humans and soil. However, some fungal pathogens, such as Histoplasma, Blastomyces, Coccidioides, Cryptococcus, and Sporothrix, have more focal areas of endemicity. Fungal bone and joint infections result from direct inoculation, contiguous infection spread, or hematogenous seeding of organisms. These infections may be difficult to diagnose and eradicate, especially in the setting of total joint arthroplasty. Although there is no clear consensus on treatment, guidelines are available for management of many of these pathogens.

  13. Fungal Genome Sequencing and Bioenergy

    SciTech Connect

    Baker, Scott E.; Thykaer, Jette; Adney, William S.; Brettin, T.; Brockman, Fred J.; D'haeseleer, Patrik; Martinez, Antonio D.; Miller, R. M.; Rokhsar, Daniel S.; Schadt, Christopher W.; Torok, Tamas; Tuskan, Gerald; Bennett, Joan W.; Berka, Randy; Briggs, Steve; Heitman, Joseph; Taylor, John; Turgeon, Barbara G.; Werner-Washburne, Maggie; Himmel, Michael E.

    2008-09-30

    To date, the number of ongoing filamentous fungal genome sequencing projects is almost tenfold fewer than those of bacterial and archaeal genome projects. The fungi chosen for sequencing represent narrow kingdom diversity; most are pathogens or models. We advocate an ambitious, forward-looking phylogenetic-based genome sequencing program, designed to capture metabolic diversity within the fungal kingdom, thereby enhancing research into alternative bioenergy sources, bioremediation, and fungal-environment interactions.

  14. Fungal pretreatment of lignocellulosic biomass.

    PubMed

    Wan, Caixia; Li, Yebo

    2012-01-01

    Pretreatment is a crucial step in the conversion of lignocellulosic biomass to fermentable sugars and biofuels. Compared to thermal/chemical pretreatment, fungal pretreatment reduces the recalcitrance of lignocellulosic biomass by lignin-degrading microorganisms and thus potentially provides an environmentally-friendly and energy-efficient pretreatment technology for biofuel production. This paper provides an overview of the current state of fungal pretreatment by white rot fungi for biofuel production. The specific topics discussed are: 1) enzymes involved in biodegradation during the fungal pretreatment; 2) operating parameters governing performance of the fungal pretreatment; 3) the effect of fungal pretreatment on enzymatic hydrolysis and ethanol production; 4) efforts for improving enzymatic hydrolysis and ethanol production through combinations of fungal pretreatment and physical/chemical pretreatment; 5) the treatment of lignocellulosic biomass with lignin-degrading enzymes isolated from fungal pretreatment, with a comparison to fungal pretreatment; 6) modeling, reactor design, and scale-up of solid state fungal pretreatment; and 7) the limitations and future perspective of this technology.

  15. Intracorneal injection of amphothericin B for recurrent fungal keratitis and endophthalmitis.

    PubMed

    Garcia-Valenzuela, Enrique; Song, C Diane

    2005-12-01

    Penetrating keratoplasty carries an infectious risk. Its requirement for topical corticosteroid therapy facilitates fungal growth with resulting keratitis. Although progression of fungal keratitis to intraocular infection is uncommon, endophthalmitis resulting from keratitis usually has a poor visual prognosis. Fungal infection under these circumstances remains a diagnostic and therapeutic challenge. We report a complicated case of recurrent fungal keratitis with endophthalmitis following a contaminated penetrating keratoplasty that ultimately was controlled with a new treatment modality. Intrastromal corneal injections combined with intravitreal injection of amphotericin B led to the eradication of the corneal fungal plaques and the intraocular infection. Intrastromal corneal injections of amphotericin B may offer a less invasive, in-office alternative to repeat penetrating keratoplasty.

  16. Real-time in vivo imaging of fungal migration to the central nervous system.

    PubMed

    Shi, Meiqing; Colarusso, Pina; Calaruso, Pina; Mody, Christopher H

    2012-12-01

    Recent technical advances have afforded valuable new insights into the pathogenesis of fungal infections in the central nervous system (CNS), which continue to cause devastating complications, particularly in immunocompromised individuals. To cause CNS mycosis, organisms such as Cryptococcus neoformans become blood borne and progress through a series of pathogenic checkpoints that culminate in fungal replication in the brain. Critical steps include fungal arrest in the vasculature of the brain, interaction and signalling of the fungal and endothelial cells leading to transmigration with subsequent parenchymal invasion and fungal replication in the CNS. Previous studies that made use of in vitro and ex vivo approaches contributed greatly to our understanding of brain invasion by fungi. However, the knowledge gained from previous studies relied on in vitro models that did not account for vascular haemodynamics. For this reason, more refined approaches that model blood flow and vascular anatomy are required, andultimately studying fungal invasion and dissemination in vivo. Indeed, in vivo imaging (also known as intravital imaging) has emerged as a valuable technique to probe host-pathogen interactions. In this review, with a focus on C. neoformans, we will provide an overview of the applications of the prior techniques and recent advances, their strengths and limitations in characterizing the migration of fungi into the brain, and unanswered questions that may provide new directions for research.

  17. Allergic Fungal Sinusitis.

    PubMed

    Correll, Daniel P; Luzi, Scott A; Nelson, Brenda L

    2015-12-01

    A 42 year old male presents with worsening pain and an increase in thick chronic drainage of the left sinus. Image studies show complete opacification of the left frontal sinus, left sphenoid sinus, and the left maxillary sinus. The patient was taken to the operating room and tissue for microscopic evaluation was obtained. The microscopic findings were classic for allergic fungal sinusitis: areas of alternating mucinous material and inflammatory cell debris and abundant Charcot-Leyden crystals. Cultures were performed and the patient began steroid therapy and desensitization therapy.

  18. Validation of AshTest as a Non-Invasive Alternative to Transjugular Liver Biopsy in Patients with Suspected Severe Acute Alcoholic Hepatitis

    PubMed Central

    Rudler, Marika; Mouri, Sarah; Charlotte, Frederic; Cluzel, Philippe; Ngo, Yen; Munteanu, Mona; Lebray, Pascal; Ratziu, Vlad; Thabut, Dominique; Poynard, Thierry

    2015-01-01

    Background/Aims According to guidelines, the histological diagnosis of severe alcoholic steatohepatitis (ASH) can require liver biopsy if a specific treatment is needed. The blood test AshTest (BioPredictive, Paris, France) has been initially validated for the non-invasive diagnosis of ASH in a large population of heavy drinkers. The aim was to validate the AshTest accuracy in the specific context of use of patients with suspected severe ASH, in order to reduce the need for transjugular biopsy before deciding treatment. Methods The reference was liver biopsy, performed using the transjugular route, classified according to its histological severity as none, minimal, moderate or severe. Biopsies were assessed by the same experienced pathologist, blinded to simultaneous AshTest results. Results A total of 123 patients with severe clinical ASH (recent jaundice and Maddrey function greater or equal to 32) were included, all had cirrhosis and 80% had EASL histological definition of ASH. 95% of patients received prednisolone; and the 2-year mortality was 63%. The high AshTest performance was confirmed both for the binary outcome [AUROC = 0.803 (95%CI 0.684–0.881)] significantly higher than the AST/ALT AUROC [0.603 (0.462–0.714); P<0.001], and for the severity of ASH-score system by the Obuchowski measures for [mean (SE) 0.902 (0.017) vs. AST/ALT 0.833 (0.023); P = 0.01], as well as for the diagnosis and severity of ballooning, PMN and Mallory bodies. According to attributability of discordances, AshTest had a 2–7% risk of 2 grades misclassification. Conclusion These results confirmed the diagnostic performance of AshTest in cirrhotic patients with severe clinical ASH, in the specific context of use of corticosteroid treatment. AshTest is an appropriate non-invasive alternative to transjugular liver biopsy. PMID:26252713

  19. Fungal Infections in Intensive Care Unit: Challenges in Diagnosis and Management

    PubMed Central

    Bajwa, SJ; Kulshrestha, A

    2013-01-01

    Infections have almost become an inseparable part of the intensive care units throughout the globe in spite of numerous advancements in diagnostic and therapeutic interventions. With advances in critical care medicine and introduction of broad-spectrum antibiotics, the incidence of invasive fungal infections in intensive care is on the rise, especially in patients with immunosuppression. The aim of this review is to collect recent information about various types of invasive fungal infections prevalent in the intensive care unit, the problems in their diagnosis and recent trends in their management. A thorough literature search was made in PubMed and Google using the following keywords for our search: Invasive fungal infection, antifungal therapy in intensive care unit, candidiasis. The major fungi implicated worldwide are Candida and Aspergillus spp., followed by Cryptococcus, Histoplasma, etc., in endemic areas. These produce a wide variety of infections that are difficult to diagnose as most of the diagnosing tests are non-specific and the culture takes a long time. An early suspicion of fungal infection with institution of appropriate antifungal therapy is mandatory for a positive outcome and to prevent development of invasive fungal infection. PMID:23919197

  20. Fungal biodiversity to biotechnology.

    PubMed

    Chambergo, Felipe S; Valencia, Estela Y

    2016-03-01

    Fungal habitats include soil, water, and extreme environments. With around 100,000 fungus species already described, it is estimated that 5.1 million fungus species exist on our planet, making fungi one of the largest and most diverse kingdoms of eukaryotes. Fungi show remarkable metabolic features due to a sophisticated genomic network and are important for the production of biotechnological compounds that greatly impact our society in many ways. In this review, we present the current state of knowledge on fungal biodiversity, with special emphasis on filamentous fungi and the most recent discoveries in the field of identification and production of biotechnological compounds. More than 250 fungus species have been studied to produce these biotechnological compounds. This review focuses on three of the branches generally accepted in biotechnological applications, which have been identified by a color code: red, green, and white for pharmaceutical, agricultural, and industrial biotechnology, respectively. We also discuss future prospects for the use of filamentous fungi in biotechnology application.

  1. Fungal morphogenetic changes inside the mammalian host.

    PubMed

    Trevijano-Contador, Nuria; Rueda, Cristina; Zaragoza, Oscar

    2016-09-01

    One of the main features of the majority of pathogenic fungi is the ability to switch between different types of morphological forms. These changes include the transition between cells of different shapes (such as the formation of pseudohyphae and hyphae), or the massive growth of the blastoconidia and formation of titan cells. Morphological changes occur during infection, and there is extensive evidence that they play a key role in processes required for disease, such as adhesion, invasion and dissemination, immune recognition evasion, and phagocytosis avoidance. In the present review, we will provide an overview of how morphological transitions contribute to the development of fungal disease, with special emphasis in two cases: Candida albicans as an example of yeast that switches between blastoconidia and filaments, and Cryptococcus neoformans as an example of a fungus that changes the size without modifying the shape of the cell.

  2. Fungal infections in immunocompromised travelers.

    PubMed

    Lortholary, Olivier; Charlier, Caroline; Lebeaux, David; Lecuit, Marc; Consigny, Paul Henri

    2013-03-01

    Immunocompromised patients represent an increasing group of travelers, for business, tourism, and visiting friends and relatives. Those with severe cellular immunodeficiency (advanced human immunodeficiency virus infection and transplant recipients) display the highest risk of fungal infections. International travel is less risky in most other types of immunodeficiency (except those with neutropenia). A systematic visit in a travel clinic for immunocompromised patients traveling to the tropics ensures that the specific risks of acquiring fungal infections (and others) are understood. When immunocompromised hosts return to their area of residence, a nonbacteriologically documented, potentially severe, febrile pneumonia, with or without dissemination signs (skin lesions, cytopenia) should alert for travel-acquired fungal infection, even years after return. Localized subcutaneous nodule may be also ascribed to fungal infection. Finally, infectious diseases physicians should be aware of major clinical patterns of travel-acquired fungal infection, as well as the fungi involved, and risk factors according to the geographical area visited.

  3. Invertebrate models of fungal infection.

    PubMed

    Arvanitis, Marios; Glavis-Bloom, Justin; Mylonakis, Eleftherios

    2013-09-01

    The morbidity, mortality and economic burden associated with fungal infections, together with the emergence of fungal strains resistant to current antimicrobial agents, necessitate broadening our understanding of fungal pathogenesis and discovering new agents to treat these infections. Using invertebrate hosts, especially the nematode Caenorhabditis elegans and the model insects Drosophila melanogaster and Galleria mellonella, could help achieve these goals. The evolutionary conservation of several aspects of the innate immune response between invertebrates and mammals makes the use of these simple hosts an effective and fast screening method for identifying fungal virulence factors and testing potential antifungal compounds. The purpose of this review is to compare several model hosts that have been used in experimental mycology to-date and to describe their different characteristics and contribution to the study of fungal virulence and the detection of compounds with antifungal properties. This article is part of a Special Issue entitled: Animal Models of Disease.

  4. [Genetic diagnosis against fungal cerebromeningitis].

    PubMed

    Ohno, Hideaki; Miyazaki, Yoshitsugu

    2013-01-01

    Fungal cerebromeningitis is one of deep seated mycoses and also a fatal fungal infectious disease. Regarding to causative pathogen of fungal cerebromeningitis in Japan, Cryptococcus spp., Candida spp., Aspergillus spp., are popular fungi. In general, the diagnosis of deep seated mycosis is sometime difficult. The genetic diagnosis method such as PCR against deep seated mycosis has been developing and it has been also reported as one of useful diagnostic tests. However, PCR for fungal detection is still a research test that has not been cleared or approved officially, therefore it should not be used for diagnosis, or patient management routinely. The PCR which detect broad range of fungi or specific fungus is applied for clinical situation, a careful attention should be paid for avoiding contamination because many fungal species are available in living environment.

  5. Standard methods for fungal brood disease research

    PubMed Central

    Jensen, Annette Bruun; Aronstein, Kathrine; Flores, José Manuel; Vojvodic, Svjetlana; Palacio, María Alejandra; Spivak, Marla

    2013-01-01

    Summary Chalkbrood and stonebrood are two fungal diseases associated with honey bee brood. Chalkbrood, caused by Ascosphaera apis, is a common and widespread disease that can result in severe reduction of emerging worker bees and thus overall colony productivity. Stonebrood is caused by Aspergillus spp. that are rarely observed, so the impact on colony health is not very well understood. A major concern with the presence of Aspergillus in honey bees is the production of airborne conidia, which can lead to allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, or even invasive aspergillosis in lung tissues upon inhalation by humans. In the current chapter we describe the honey bee disease symptoms of these fungal pathogens. In addition, we provide research methodologies and protocols for isolating and culturing, in vivo and in vitro assays that are commonly used to study these host pathogen interactions. We give guidelines on the preferred methods used in current research and the application of molecular techniques. We have added photographs, drawings and illustrations to assist bee-extension personnel and bee scientists in the control of these two diseases. PMID:24198438

  6. Fungal endophthalmitis associated with compounded products.

    PubMed

    Mikosz, Christina A; Smith, Rachel M; Kim, Moon; Tyson, Clara; Lee, Ellen H; Adams, Eleanor; Straif-Bourgeois, Susanne; Sowadsky, Rick; Arroyo, Shannon; Grant-Greene, Yoran; Duran, Julie; Vasquez, Yvonne; Robinson, Byron F; Harris, Julie R; Lockhart, Shawn R; Török, Thomas J; Mascola, Laurene; Park, Benjamin J

    2014-02-01

    Fungal endophthalmitis is a rare but serious infection. In March 2012, several cases of probable and laboratory-confirmed fungal endophthalmitis occurring after invasive ocular procedures were reported nationwide. We identified 47 cases in 9 states: 21 patients had been exposed to the intraocular dye Brilliant Blue G (BBG) during retinal surgery, and the other 26 had received an intravitreal injection containing triamcinolone acetonide. Both drugs were produced by Franck's Compounding Lab (Ocala, FL, USA). Fusarium incarnatum-equiseti species complex mold was identified in specimens from BBG-exposed case-patients and an unopened BBG vial. Bipolaris hawaiiensis mold was identified in specimens from triamcinolone-exposed case-patients. Exposure to either product was the only factor associated with case status. Of 40 case-patients for whom data were available, 39 (98%) lost vision. These concurrent outbreaks, associated with 1 compounding pharmacy, resulted in a product recall. Ensuring safety and integrity of compounded medications is critical for preventing further outbreaks associated with compounded products.

  7. [Prevention of fungal infections in hospitalized patients].

    PubMed

    Seeliger, H P; Schröter, G

    1984-06-01

    Hospital acquired infections due to fungi are primarily caused by yeast species of the genus Candida and mould species of the genus Aspergillus. Underlying disease with severely impaired defence mechanisms as well as certain forms of immunosuppressive and aggressive chemotherapy are the most important prerequisites for such secondary fungal infections. Aspergillus spec. usually infect man via exogenous routes, whereas Candida spec. mostly originate from the patient's own microbial flora. Under certain circumstances invasion of tissues follows (endomycosis). Exogenous Candida infections may likewise occur through contaminated hands of personnel and medical devices. The density of yeast cell distribution in hospital wards decreases with the distance from the primary source: the Candida infected human patient. Preventive measures protecting the patient at risk include: Permanent surveillance by routine cultural and serological examinations for the detection of an early infection of the skin, mouth, oesophagus, urinary tract, vagina and the bowel. Monitoring of patients is essential for early detection of dissemination and contributes to the control of fungal decontamination measures. Selective local decontamination is effected by the use of nonabsorbable compounds such as nystatin and amphotericin B in the gastrointestinal tract, and in oral and genital mucous membranes. Oral administration of ketoconazole has also been recommended. For the disinfection of skin appropriate chemicals are available. In the control of the environment of the endangered patient special attention must be paid to meticulous management of catheters. These measures are to be supported by careful disinfection policy concerning the hands of personnel and medical equipment.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Burden of serious fungal infections in Mexico.

    PubMed

    Corzo-León, D E; Armstrong-James, D; Denning, D W

    2015-10-01

    Serious fungal infections (SFIs) could be more frequent than are recognised. Estimates of the incidence and prevalence of SFIs are essential in order to identify public health problems. We estimated the rates of SFIs in Mexico, following a methodology similar to that used in prior studies. We obtained information about the general population and populations at risk. A systematic literature search was undertaken to identify epidemiological reports of SFIs in Mexico. When Mexican reports were unavailable, we based our estimates on international literature. The most prevalent SFIs in Mexico are recurrent vulvovaginal candidiasis (5999 per 100,000) followed by allergic bronchopulmonary aspergillosis (60 per 100,000), chronic pulmonary aspergillosis (15.9 per 100,000), fungal keratitis (10.4 per 100,000), invasive candidiasis (8.6 per 100,000) and SFIs in HIV (8.2 per 100,000); coccidioidomycosis (7.6 per 100,000), IA (4.56 per 100,000). These correspond to 2,749,159 people affected in any year (2.45% of the population), probably >10,000 deaths and 7000 blind eyes. SFIs affect immunocompromised and healthy populations. Most are associated with high morbidity and mortality rates. Validation of these estimates with epidemiological studies is required. The burdens indicate that an urgent need to improve medical skills, surveillance, diagnosis, and management of SFIs exists.

  9. Standard methods for fungal brood disease research.

    PubMed

    Jensen, Annette Bruun; Aronstein, Kathrine; Flores, José Manuel; Vojvodic, Svjetlana; Palacio, María Alejandra; Spivak, Marla

    2013-01-01

    Chalkbrood and stonebrood are two fungal diseases associated with honey bee brood. Chalkbrood, caused by Ascosphaera apis, is a common and widespread disease that can result in severe reduction of emerging worker bees and thus overall colony productivity. Stonebrood is caused by Aspergillus spp. that are rarely observed, so the impact on colony health is not very well understood. A major concern with the presence of Aspergillus in honey bees is the production of airborne conidia, which can lead to allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, or even invasive aspergillosis in lung tissues upon inhalation by humans. In the current chapter we describe the honey bee disease symptoms of these fungal pathogens. In addition, we provide research methodologies and protocols for isolating and culturing, in vivo and in vitro assays that are commonly used to study these host pathogen interactions. We give guidelines on the preferred methods used in current research and the application of molecular techniques. We have added photographs, drawings and illustrations to assist bee-extension personnel and bee scientists in the control of these two diseases.

  10. Mycobacterium kansasii Pneumonia with Mediastinal Lymphadenitis in a Patient with Acute Myeloid Leukemia: Successful Treatment to Stem Cell Transplantation

    PubMed Central

    Choi, Yeon-Geun; Lee, Dong-Gun; Yim, Eunjung; Joo, Hyonsoo; Ryu, Seongyul; Choi, Jae-Ki; Kim, Hee-Je

    2017-01-01

    Non-tuberculous mycobacterial (NTM) disease is a relatively rare cause of neutropenic fever in patients with hematologic malignancies. During the neutropenic period, performing invasive procedures for microbiological or pathological confirmation is difficult. In addition, the optimal treatment duration for NTM disease in patients with leukemia, especially prior to stem cell transplantation (SCT), has not been documented. Therefore, we report a case of pneumonia with necrotizing lymphadenitis caused by Mycobacterium kansasii diagnosed during chemotherapy being performed for acute myeloid leukemia. The radiologic findings were similar to those of invasive fungal pneumonia; however, a bronchoalveolar washing fluid culture confirmed that the pathogen was M. kansasii. After 70 days from starting NTM treatment, allogeneic SCT was performed without any complications. The patient fully recovered after 12 months of NTM treatment, and neither reactivation of M. kansasii infection nor related complications were reported. PMID:28271647

  11. [Successful treatment of a persistent rhino-cerebral mucormycosis in a pediatric patient with a debut of acute lymphoblastic leukemia].

    PubMed

    Cofré, Fernanda; Villarroel, Milena; Castellón, Loreto; Santolaya, María E

    2015-08-01

    The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.

  12. Invasive Candidiasis.

    PubMed

    McCarty, Todd P; Pappas, Peter G

    2016-03-01

    Invasive candidiasis is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 5 of which cause most cases. Candidemia is the most commonly recognized syndrome associated with invasive candidiasis. Certain conditions may influence the likelihood for one species versus another in a specific clinical scenario, and this can have important implications for selection of antifungal therapy and the duration of treatment. Molecular diagnostic technology plays an ever-increasing role as an adjunct to traditional culture-based diagnostics, offering significant potential toward improvement in patient care.

  13. Orbital Apex Syndrome in a Patient with Sphenoid Fungal Balls

    PubMed Central

    Jin, Bong Joon; Lee, Yong Seop; Paik, Seung Sam; Ko, Myung Kyoo; Yi, Hyeong-Joong

    2009-01-01

    Orbital apex syndrome (OAS) is a rare disease that presents with a complex of symptoms, including ophthalmoplegia, ptosis and visual loss. Due to the poor prognosis, making a prompt diagnosis and administering the appropriate treatment must be initiated without delay if OAS is suspected. We report here on a case of a patient with sphenoid fungal balls, and he presented with acute visual loss and ophthalmoplegia. PMID:19434293

  14. Orbital apex syndrome in a patient with sphenoid fungal balls.

    PubMed

    Cho, Seok Hyun; Jin, Bong Joon; Lee, Yong Seop; Paik, Seung Sam; Ko, Myung Kyoo; Yi, Hyeong-Joong

    2009-03-01

    Orbital apex syndrome (OAS) is a rare disease that presents with a complex of symptoms, including ophthalmoplegia, ptosis and visual loss. Due to the poor prognosis, making a prompt diagnosis and administering the appropriate treatment must be initiated without delay if OAS is suspected. We report here on a case of a patient with sphenoid fungal balls, and he presented with acute visual loss and ophthalmoplegia.

  15. Superficial fungal infections.

    PubMed

    Schwartz, Robert A

    Superficial fungal infections arise from a pathogen that is restricted to the stratum corneum, with little or no tissue reaction. In this Seminar, three types of infection will be covered: tinea versicolor, piedra, and tinea nigra. Tinea versicolor is common worldwide and is caused by Malassezia spp, which are human saprophytes that sometimes switch from yeast to pathogenic mycelial form. Malassezia furfur, Malassezia globosa, and Malassezia sympodialis are most closely linked to tinea versicolor. White and black piedra are both common in tropical regions of the world; white piedra is also endemic in temperate climates. Black piedra is caused by Piedraia hortae; white piedra is due to pathogenic species of the Trichosporon genus. Tinea nigra is also common in tropical areas and has been confused with melanoma.

  16. Epidemiology and risk factors for invasive candidiasis

    PubMed Central

    Yapar, Nur

    2014-01-01

    The number of immunosuppressive patients has increased significantly in recent years. These patients are at risk for opportunistic infections, especially fungal infections. Candidiasis is one of the most frequent fungal infections determined in these immunosuppressive patients and its epidemiology has changed over the last two decades. Recently, new antifungal agents and new therapy strategies such as antifungal prophylaxis, secondary prophylaxis, and preemptive therapy have come into use. These changes resulted in the alteration of Candida species causing invasive infections. The incidence of Candida albicans was decreased in many countries, especially among patients with immunosuppressive disorders, while the incidence of species other than C. albicans was increased. In this review, incidence, risk factors, and species distribution of invasive candidiasis are discussed. PMID:24611015

  17. An estimate of the burden of serious fungal diseases in Greece.

    PubMed

    Gamaletsou, M N; Drogari-Apiranthitou, M; Denning, D W; Sipsas, N V

    2016-07-01

    Data on the epidemiology of serious fungal infections in Greece are scarce. Our aim was to calculate the burden of serious fungal diseases in Greece. A thorough literature search for papers reporting epidemiological data on serious fungal diseases in Greece was performed. Where no Greek data existed, we used a structured set of assumptions to estimate fungal disease burden, based on specific high-risk populations. Of the 10.8 million population, 85.5 % are adults and 27 % are over 60 years of age. The annual fungal disease estimates are as follows: 142,337 Greek women get recurrent vaginal thrush (2,632 cases/100,000 females); there are 889 cases of esophageal candidiasis (8.2 cases/100,000); annual incidence of Pneumocystis pneumonia is 112 cases; chronic pulmonary aspergillosis prevalence is 386 cases; there are 20,843 patients with allergic bronchopulmonary aspergillosis and 27,744 with severe asthma with fungal sensitization; candidaemia incidence is 541 cases (5.0/100,000); there are 81 cases of Candida peritonitis; invasive aspergillosis occurs in 1,125 patients. According to our calculations, 194,067 individuals (1.79 cases/100,000) in Greece suffer from serious fungal diseases each year. This is the first attempt to determine the burden of fungal diseases in Greece, and provides a crude estimate on its impact on public health.

  18. The acute phase protein ceruloplasmin as a non-invasive marker of pseudopregnancy, pregnancy, and pregnancy loss in the giant panda.

    PubMed

    Willis, Erin L; Kersey, David C; Durrant, Barbara S; Kouba, Andrew J

    2011-01-01

    After ovulation, non-pregnant female giant pandas experience pseudopregnancy. During pseudopregnancy, non-pregnant females exhibit physiological and behavioral changes similar to pregnancy. Monitoring hormonal patterns that are usually different in pregnant mammals are not effective at determining pregnancy status in many animals that undergo pseudopregnancy, including the giant panda. Therefore, a physiological test to distinguish between pregnancy and pseudopregnancy in pandas has eluded scientists for decades. We examined other potential markers of pregnancy and found that activity of the acute phase protein ceruloplasmin increases in urine of giant pandas in response to pregnancy. Results indicate that in term pregnancies, levels of active urinary ceruloplasmin were elevated the first week of pregnancy and remain elevated until 20-24 days prior to parturition, while no increase was observed during the luteal phase in known pseudopregnancies. Active ceruloplasmin also increased during ultrasound-confirmed lost pregnancies; however, the pattern was different compared to term pregnancies, particularly during the late luteal phase. In four out of the five additional reproductive cycles included in the current study where females were bred but no birth occurred, active ceruloplasmin in urine increased during the luteal phase. Similar to the known lost pregnancies, the temporal pattern of change in urinary ceruloplasmin during the luteal phase deviated from the term pregnancies suggesting that these cycles may have also been lost pregnancies. Among giant pandas in captivity, it has been presumed that there is a high rate of pregnancy loss and our results are the first to provide evidence supporting this notion.

  19. Recent Advances in Invasive Cardiology

    PubMed Central

    Garbe, George J.

    1987-01-01

    This paper describes recent advances in invasive cardiology that enable the primary-care physician to offer his/her patient a wider range of effective treatments. Major developments in the investigation and management of the acute coronary syndromes, unstable angina and myocardial infarction, have revolutionized the care of patients with these conditions. The primary-care physician must be aware of the treatment modalities, the lines of referral, and strategies for management available in his/her clinical setting to allow prompt application of these modalities. A sampling of exciting advances in other areas of invasive cardiology are also described. PMID:21263906

  20. Fungal arthritis of the hip in patient with aplastic anaemia.

    PubMed

    Le Calloch, Ronan; Ianotto, Jean-Christophe; Guillerm, Gaëlle; Tonnelier, Jean Marie

    2013-08-13

    Aplastic anaemia is a rare and serious disease characterised by severe immunosuppression due to prolonged neutropenia and the use of immunosuppressants such as corticosteroids, cyclosporine and antithymocyte globulin. Candida species are pathogens of low virulence colonising the skin and the digestive tract of many healthy individuals. Nonetheless, the incidence of invasive candidal infection is increasing. The widespread use of central intravascular catheters, invasive procedures, broad-spectrum antibiotics and immunosuppresion predisposes patients to these infections. Eye, skin, cardiac, liver, spleen and brain infection are the most common sites of invasive candidiasis. Bone and joint infections are less frequent and Candida hip septic arthritis is extremely rare. We present here a patient treated for aplastic anaemia, who developed fungal arthritis of the hip and systemic candidaemia.

  1. Serious fungal infections in Korea.

    PubMed

    Huh, K; Ha, Y E; Denning, D W; Peck, K R

    2017-02-04

    Information on the incidence and prevalence of fungal infections is of critical value in public health policy. However, nationwide epidemiological data on fungal infections are scarce, due to a lack of surveillance and funding. The objective of this study was to estimate the disease burden of fungal infections in the Republic of Korea. An actuarial approach using a deterministic model was used for the estimation. Data on the number of populations at risk and the frequencies of fungal infections in those populations were obtained from national statistics reports and epidemiology papers. Approximately 1 million people were estimated to be affected by fungal infections every year. The burdens of candidemia (4.12 per 100,000), cryptococcal meningitis (0.09 per 100,000), and Pneumocystis pneumonia (0.51 per 100,000) in South Korea were estimated to be comparable to those in other countries. The prevalence of chronic pulmonary aspergillosis (22.4 per 100,000) was markedly high, probably due to the high burden of tuberculosis in Korea. The low burdens of allergic bronchopulmonary aspergillosis (56.9 per 100,000) and severe asthma with fungal sensitization (75.1 per 100,000) warrant further study. Oral candidiasis (539 per 100,000) was estimated to affect a much larger population than noted in previous studies. Our work provides valuable insight on the epidemiology of fungal infections; however, additional studies are needed.

  2. [Invasive maxilar sinusitis by Rhizopus oryzae].

    PubMed

    Perea, S; del Palacio, A; Gil, R; de la Serna, J; Mata, R; Arribi, A

    1997-12-01

    We herein present a diabetic with non Hodgkin lymphoma patient that had been treated with steroids and developed fungal invasive sinusitis. The patient had intensive facial pain that did not respond to antibiotics and on clinical inspection had a necrotic lesion on right nasal area. A smear and biopsy tissue showed broad non septate hyphae and on cultures Rhizopus oryzae was isolated. There was an unfavorable outcome, and the patient died even though liposomal Amphotericin B was administered and surgical treatment was performed.

  3. Performance of Galactomannan Antigen, Beta-d-Glucan, and Aspergillus-Lateral-Flow Device for the Diagnosis of Invasive Aspergillosis.

    PubMed

    Metan, Gökhan; Keklik, Muzaffer; Dinç, Gökçen; Pala, Çiğdem; Yıldırım, Afra; Saraymen, Berkay; Köker, Mustafa Yavuz; Kaynar, Leylagül; Eser, Bülent; Çetin, Mustafa

    2017-03-01

    Aspergillus lateral-flow device (LFD) was recently introduced as a practical tool for the diagnosis of invasive aspergillosis (IA). We investigated the performance of Aspergillus-LFD as a point-of-care test for the diagnosis of IA. Serum samples were collected twice weekly from patients who received intensive chemotherapy for acute leukemia, or recepients of allogeneic stem cell transplantation. Aspergillus galactomannan (GM) antigen, 1,3-beta-d-glucan and Aspergillus-LFD tests were carried out according to manufacturers' recommendations. GM testing was repeated with a modified procedure which was proven to increase the sensitivity. Aspergillus-LFD was performed without applying any pretreatment procedure to allow the kit to fit as a point-of-care test. Fungal infections were categorized according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. A total of 75 neutropenia episodes in 64 patients were prospectively followed between February 2012 and January 2013. Probable IA was diagnosed in 11 patients, probable pulmonary fungal disease was diagnosed in one patient, and rhinocerebral aspergillosis was diagnosed in one patient. Fungemia was detected in two patients. Aspergillus-LFD was positive in serum of a patient with probable IA and in the bronchoalveolar lavage fluid of an other patient with probable IA. Aspergillus-LFD was false positive in serum of two patients. Although there was no radiological finding of IA or documented fungemia, fever resolved after empirical caspofungin therapy in one of these patients. The sensitivity of Aspergillus-LFD as a point-of-care test without any pretreatment of serum sample is low.

  4. Advances and prospects for molecular diagnostics of fungal infections.

    PubMed

    Bretagne, Stéphane

    2010-11-01

    The polymerase chain reaction (PCR) methods published for the diagnosis of invasive fungal infections are still not included in the revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions of IA. This could be achieved with consensual PCR procedures. A checklist of items has been proposed to improve the reliability of the results and clinicians' confidence in them, with emphasis on limiting false-positive results from contamination with either previously amplified products or environmental commensals. Internal amplification controls are mandatory to expose false-negative results. However, our ignorance of the origin and the kinetics of fungal DNA during an infection hamper the choice of the best specimen and DNA extraction protocol. Evidence is increasing that serum could be a good compromise between sensitivity and ease of DNA extraction. Once a technical consensus is achieved, clinical studies should be initiated to integrate quantitative PCR in the diagnostic armamentarium.

  5. Histopathologic Diagnosis of Fungal Infections in the 21st Century

    PubMed Central

    Guarner, Jeannette; Brandt, Mary E.

    2011-01-01

    Summary: Fungal infections are becoming more frequent because of expansion of at-risk populations and the use of treatment modalities that permit longer survival of these patients. Because histopathologic examination of tissues detects fungal invasion of tissues and vessels as well as the host reaction to the fungus, it is and will remain an important tool to define the diagnostic significance of positive culture isolates or results from PCR testing. However, there are very few instances where the morphological characteristics of fungi are specific. Therefore, histopathologic diagnosis should be primarily descriptive of the fungus and should include the presence or absence of tissue invasion and the host reaction to the infection. The pathology report should also include a comment stating the most frequent fungi associated with that morphology as well as other possible fungi and parasites that should be considered in the differential diagnosis. Alternate techniques have been used to determine the specific agent present in the histopathologic specimen, including immunohistochemistry, in situ hybridization, and PCR. In addition, techniques such as laser microdissection will be useful to detect the now more frequently recognized dual fungal infections and the local environment in which this phenomenon occurs. PMID:21482725

  6. [Experimental models of acute pancreatitis].

    PubMed

    Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur

    2015-02-21

    Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.

  7. Pharmacokinetics of posaconazole prophylaxis of patients with acute myeloid leukemia.

    PubMed

    Mattiuzzi, Gloria; Yilmaz, Musa; Kantarjian, Hagop; Borthakur, Gautam; Konopleva, Marina; Jabbour, Elias; Brown, Yolanda; Pierce, Sherry; Cortes, Jorge

    2015-09-01

    Antifungal prophylaxis is routinely given to patients with hematologic malignancies at high risk for invasive fungal infections (IFI), yet breakthrough IFI may still occur. Posaconazole emerged as an excellent alternative for fungal prophylaxis in high-risk patients. There is limited data about pharmacokinetics and plasma concentrations of posaconazole when given as prophylaxis in patients with hematologic malignancies. We recruited 20 adult patients for prospective, open label trial of posaconazole given as a prophylaxis in patients with newly diagnosed acute myeloid leukemia (AML) undergoing induction chemotherapy or first salvage therapy. The median age of all patients was 65 years and received prophylaxis for a median of 38 days (range: 5-42 days).Ten patients (50%) completed 42 days on posaconazole prophylaxis. Median plasma posaconazole levels showed no statistical difference across gender, body surface area, patients developing IFI, and patients acquiring grade 3 or 4 elevation of liver enzymes. However, there was an overall trend for higher trough concentrations among patients with no IFI than those with IFI. Pharmacokinetics of posaconazole varies from patient to patient, and AML patients receiving induction chemotherapy who never develop IFI tend to have higher plasma concentrations after oral administration of posaconazole.

  8. Fungal Infections of the Ear in Immunocompromised Host: a Review

    PubMed Central

    Viswanatha, Borlingegowda; Naseeruddin, Khaja

    2011-01-01

    Otomycosis is a fungal infection of the external ear; middle ear and open mastoid cavity.1 Meyer first described the fungal infection of the external ear canal in 1884. External ear canal has an ideal warm humid environment for the proliferation of fungus.2 Although this disease is rarely life threatening, it can presents a challenging and frustrating situation for the otologist and patients due to long term treatment and high rate of recurrence.3 Otomycosis is seen more frequently in immunocompromised patients as compared to immunocompetent persons. Recurrence rate is high in immunocompromised patients and they need longer duration treatment and complications are more frequent in immunocompromised patients. In the recent years; opportunistic fungal infections are gaining greater importance in human medicine as a result of possibly huge number of immunocompromised patients.4 In immunocompromised patients, it is important that the treatment of otomycosis be vigorous, to minimize complications such as hearing loss, tympanic membrane perforations and invasive temporal bone infection.5 Fungal cultures are essential to confirm the diagnosis. Hematological investigations play a very important role in confirming the diagnosis and immunity status of the patients. In diabetic patients with otomycosis, along with antifungal therapy, blood sugar levels should be controlled with medical therapy to prevent complications. PMID:21625307

  9. Traversing the fungal terpenome

    PubMed Central

    Quin, Maureen B.; Flynn, Christopher M.; Schmidt-Dannert, Claudia

    2014-01-01

    Fungi (Ascomycota and Basidiomycota) are prolific producers of structurally diverse terpenoid compounds. Classes of terpenoids identified in fungi include the sesqui-, di- and triterpenoids. Biosynthetic pathways and enzymes to terpenoids from each of these classes have been described. These typically involve the scaffold generating terpene synthases and cyclases, and scaffold tailoring enzymes such as e.g. cytochrome P450 monoxygenases, NAD(P)+ and flavin dependent oxidoreductases, and various group transferases that generate the final bioactive structures. The biosynthesis of several sesquiterpenoid mycotoxins and bioactive diterpenoids has been well-studied in Ascomycota (e.g. filamentous fungi). Little is known about the terpenoid biosynthetic pathways in Basidiomycota (e.g. mushroom forming fungi), although they produce a huge diversity of terpenoid natural products. Specifically, many trans-humulyl cation derived sesquiterpenoid natural products with potent bioactivities have been isolated. Biosynthetic gene clusters responsible for the production of trans-humulyl cation derived protoilludanes, and other sesquiterpenoids, can be rapidly identified by genome sequencing and bioinformatic methods. Genome mining combined with heterologous biosynthetic pathway refactoring has the potential to facilitate discovery and production of pharmaceutically relevant fungal terpenoids. PMID:25171145

  10. Comparison of minimally invasive surgery with standard open surgery for vertebral thoracic metastases causing acute myelopathy in patients with short- or mid-term life expectancy: surgical technique and early clinical results.

    PubMed

    Miscusi, Massimo; Polli, Filippo Maria; Forcato, Stefano; Ricciardi, Luca; Frati, Alessandro; Cimatti, Marco; De Martino, Luca; Ramieri, Alessandro; Raco, Antonino

    2015-05-01

    OBJECT Spinal metastasis is common in patients with cancer. About 70% of symptomatic lesions are found in the thoracic region of the spine, and cord compression presents as the initial symptom in 5%-10% of patients. Minimally invasive spine surgery (MISS) has recently been advocated as a useful approach for spinal metastases, with the aim of decreasing the morbidity associated with more traditional open spine surgery; furthermore, the recovery time is reduced after MISS, such that postoperative chemotherapy and radiotherapy can begin sooner. METHODS Two series of oncological patients, who presented with acute myelopathy due to vertebral thoracic metastases, were compared in this study. Patients with complete paraplegia for more than 24 hours and with a modified Bauer score greater than 2 were excluded from the study. The first group (n = 23) comprised patients who were prospectively enrolled from May 2010 to September 2013, and who were treated with minimally invasive laminotomy/laminectomy and percutaneous stabilization. The second group (n = 19) comprised patients from whom data were retrospectively collected before May 2010, and who had been treated with laminectomy and stabilization with traditional open surgery. Patient groups were similar regarding general characteristics and neurological impairment. Results were analyzed in terms of neurological recovery (American Spinal Injury Association grade), complications, pain relief (visual analog scale), and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and EORTC QLQ-BM22 scales) at the 30-day follow-up. Operation time, postoperative duration of bed rest, duration of hospitalization, intraoperative blood loss, and the need and length of postoperative opioid administration were also evaluated. RESULTS There were no significant differences between the 2 groups in terms of neurological recovery and complications. Nevertheless, the MISS group showed a clear and significant

  11. Mutualistic fungus promotes plant invasion into diverse communities.

    PubMed

    Rudgers, Jennifer A; Mattingly, W Brett; Koslow, Jennifer M

    2005-07-01

    Reducing the biological diversity of a community may decrease its resistance to invasion by exotic species. Manipulative experiments typically support this hypothesis but have focused mainly on one trophic level (i.e., primary producers). To date, we know little about how positive interactions among species may influence the relationship between diversity and invasibility, which suggests a need for research that addresses the question: under what conditions does diversity affect resistance to invasion? We used experimental manipulations of both plant diversity and the presence of an endophytic fungus to test whether a fungal mutualist of an invasive grass species (Lolium arundinaceum) switches the relationship between plant community diversity and resistance to invasion. Association with the fungal endophyte (Neotyphodium coenophialum) increased the ability of L. arundinaceum to invade communities with greater species diversity. In the absence of the endophyte, the initial diversity of the community significantly reduced the establishment of L. arundinaceum. However, establishment was independent of initial diversity in the presence of the endophyte. Fungal symbionts, like other key species, are often overlooked in studies of plant diversity, yet their presence may explain variation among studies in the effect of diversity on resistance to invasion.

  12. Fungal infections: a growing threat.

    PubMed Central

    Dixon, D M; McNeil, M M; Cohen, M L; Gellin, B G; La Montagne, J R

    1996-01-01

    THE EMERGENCE OF newly identified fungal pathogens and the reemergence of previously uncommon fungal diseases is primarily related to increases in the numbers of susceptible persons: people with HIV infection, bone marrow and organ transplant recipients, cancer patients being treated with chemotherapy, critically ill persons, and very low birth weight ( < or = 1500 g) infants. These immunocompromised populations are at risk for infection not only with opportunistic pathogens (for example, Pneumocystis, Candida, Cryptococcus, Trichosporon, Malassezia, Aspergillus, Penicillium marneffei, and numerous other moulds or yeasts) but also with fungal pathogens that usually infect otherwise healthy persons not previously exposed to endemic fungi (for example, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis) and Sporothrix schenckii. Morbidity, mortality, and health care costs associated with fungal infections are high. Addressing the emergence of fungal diseases will require increased surveillance coupled with the availability of rapid, noninvasive diagnostic tests; monitoring the development of resistance to antifungal agents; and research focused on the understanding, prevention, and control of fungal infections. Images p[227]-a p226-a p232-a PMID:8643813

  13. Structural Analysis of Fungal Cerebrosides

    PubMed Central

    Barreto-Bergter, Eliana; Sassaki, Guilherme L.; de Souza, Lauro M.

    2011-01-01

    Of the ceramide monohexosides (CMHs), gluco- and galactosyl-ceramides are the main neutral glycosphingolipids expressed in fungal cells. Their structural determination is greatly dependent on the use of mass spectrometric techniques, including fast atom bombardment-mass spectrometry, electrospray ionization, and energy collision-induced dissociation mass spectrometry. Nuclear magnetic resonance has also been used successfully. Such a combination of techniques, combined with classical analytical separation, such as high-performance thin layer chromatography and column chromatography, has led to the structural elucidation of a great number of fungal CMHs. The structure of fungal CMH is conserved among fungal species and consists of a glucose or galactose residue attached to a ceramide moiety containing 9-methyl-4,8-sphingadienine with an amidic linkage to hydroxylated fatty acids, most commonly having 16 or 18 carbon atoms and unsaturation between C-3 and C-4. Along with their unique structural characteristics, fungal CMHs have a peculiar subcellular distribution and striking biological properties. Fungal cerebrosides were also characterized as antigenic molecules directly or indirectly involved in cell growth or differentiation in Schizophyllum commune, Cryptococcus neoformans, Pseudallescheria boydii, Candida albicans, Aspergillus nidulans, Aspergillus fumigatus, and Colletotrichum gloeosporioides. Besides classical techniques for cerebroside (CMH) analysis, we now describe new approaches, combining conventional thin layer chromatography and mass spectrometry, as well as emerging technologies for subcellular localization and distribution of glycosphingolipids by secondary ion mass spectrometry and imaging matrix-assisted laser desorption ionization time-of-flight. PMID:22164155

  14. Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses.

    PubMed

    Rex, J H; Walsh, T J; Nettleman, M; Anaissie, E J; Bennett, J E; Bow, E J; Carillo-Munoz, A J; Chavanet, P; Cloud, G A; Denning, D W; de Pauw, B E; Edwards Jr, J E; Hiemenz, J W; Kauffman, C A; Lopez-Berestein, G; Martino, P; Sobel, J D; Stevens, D A; Sylvester, R; Tollemar, J; Viscoli, C; Viviani, M A; Wu, T

    2001-07-01

    Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area.

  15. New method of preoxygenation for orotracheal intubation in patients with hypoxaemic acute respiratory failure in the intensive care unit, non-invasive ventilation combined with apnoeic oxygenation by high flow nasal oxygen: the randomised OPTINIV study protocol

    PubMed Central

    Jaber, Samir; Molinari, Nicolas; De Jong, Audrey

    2016-01-01

    Introduction Tracheal intubation in the intensive care unit (ICU) is associated with severe life-threatening complications including severe hypoxaemia. Preoxygenation before intubation has been recommended in order to decrease such complications. Non-invasive ventilation (NIV)-assisted preoxygenation allows increased oxygen saturation during the intubation procedure, by applying a positive end-expiratory pressure (PEEP) to prevent alveolar derecruitment. However, the NIV mask has to be taken off after preoxygenation to allow the passage of the tube through the mouth. The patient with hypoxaemia does not receive oxygen during this period, at risk of major hypoxaemia. High-flow nasal cannula oxygen therapy (HFNC) has a potential for apnoeic oxygenation during the apnoea period following the preoxygenation with NIV. Whether application of HFNC combined with NIV is more effective at reducing oxygen desaturation during the intubation procedure compared with NIV alone for preoxygenation in patients with hypoxaemia in the ICU with acute respiratory failure remains to be established. Methods and analysis The HFNC combined to NIV for decreasing oxygen desaturation during the intubation procedure in patients with hypoxaemia in the ICU (OPTINIV) trial is an investigator-initiated monocentre randomised controlled two-arm trial with assessor-blinded outcome assessment. The OPTINIV trial randomises 50 patients with hypoxaemia requiring orotracheal intubation for acute respiratory failure to receive NIV (pressure support=10, PEEP=5, fractional inspired oxygen (FiO2)=100%) combined with HFNC (flow=60 L/min, FiO2=100%, interventional group) or NIV alone (reference group) for preoxygenation. The primary outcome is lowest oxygen saturation during the intubation procedure. Secondary outcomes are intubation-related complications, quality of preoxygenation and ICU mortality. Ethics and dissemination The study project has been approved by the appropriate ethics committee (CPP Sud

  16. Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy.

    PubMed

    Calandra, Thierry; Roberts, Jason A; Antonelli, Massimo; Bassetti, Matteo; Vincent, Jean-Louis

    2016-05-27

    Invasive fungal infections, particularly those caused by Candida species, are not uncommon in critically ill patients and are associated with considerable morbidity and mortality. Diagnosis and management of these infections can be challenging. In this review, we will briefly discuss recent epidemiological data on invasive candidiasis and current diagnostic approaches before concentrating on antifungal treatments.

  17. Calcium signaling during reproduction and biotrophic fungal interactions in plants.

    PubMed

    Chen, Junyi; Gutjahr, Caroline; Bleckmann, Andrea; Dresselhaus, Thomas

    2015-04-01

    Many recent studies have indicated that cellular communications during plant reproduction, fungal invasion, and defense involve identical or similar molecular players and mechanisms. Indeed, pollen tube invasion and sperm release shares many common features with infection of plant tissue by fungi and oomycetes, as a tip-growing intruder needs to communicate with the receptive cells to gain access into a cell and tissue. Depending on the compatibility between cells, interactions may result in defense, invasion, growth support, or cell death. Plant cells stimulated by both pollen tubes and fungal hyphae secrete, for example, small cysteine-rich proteins and receptor-like kinases are activated leading to intracellular signaling events such as the production of reactive oxygen species (ROS) and the generation of calcium (Ca(2+)) transients. The ubiquitous and versatile second messenger Ca(2+) thereafter plays a central and crucial role in modulating numerous downstream signaling processes. In stimulated cells, it elicits both fast and slow cellular responses depending on the shape, frequency, amplitude, and duration of the Ca(2+) transients. The various Ca(2+) signatures are transduced into cellular information via a battery of Ca(2+)-binding proteins. In this review, we focus on Ca(2+) signaling and discuss its occurrence during plant reproduction and interactions of plant cells with biotrophic filamentous microbes. The participation of Ca(2+) in ROS signaling pathways is also discussed.

  18. Invasive Trichosporon cutaneum infection in an infant with wilms’ tumor

    PubMed Central

    de Carvalho, Ana Maria Rabelo; de Melo, Luciana Resende Bandeira; Moraes, Vera Lúcia; Neves, Rejane Pereira

    2008-01-01

    Fungal infections are increasingly being reported in immuno-compromised patients. In this study we report a case of systemic Trichosporon cutaneum infection in an infant with Wilms’ tumor. This is the first time that an invasive infection for T. cutaneum has been reported in a Wilms’ tumor patient. PMID:24031179

  19. Posaconazole: Use in the Prophylaxis and Treatment of Fungal Infections.

    PubMed

    Clark, Nina M; Grim, Shellee A; Lynch, Joseph P

    2015-10-01

    Posaconazole, a fluorinated triazole antifungal drug, is approved by the U.S. Food and Drug Administration (FDA) for (1) prophylaxis against Aspergillus and Candida infections in immunocompromised patients at high risk for these infections and (2) oropharyngeal candidiasis (OPC), including cases refractory to fluconazole and/or itraconazole. The European Medicines Agency (EMA) has approved posaconazole for (1) treatment of aspergillosis, fusariosis, chromoblastomycosis, and coccidioidomycosis in patients who are refractory to or intolerant of other azoles or amphotericin B; (2) first-line therapy for OPC for severe disease or in those unlikely to respond to topical therapy; and (3) prophylaxis of invasive fungal infections in high-risk hematologic patients and stem cell transplant recipients. In addition to approved indications, posaconazole has been used with success as salvage therapy for invasive mold infections and endemic mycoses in patients who are refractory to or intolerant of other antifungal agents, and as prophylaxis or salvage therapy in children, for whom indications are more limited owing to a paucity of data. Posaconazole has potent in vitro activity against a broad range of fungi and molds, including Aspergillus, Candida, Cryptococcus, filamentous fungi, and endemic mycoses including coccidioidomycosis, histoplasmosis, and blastomycosis. Importantly, posaconazole is much more active than other azoles against many Mucorales species and the combination of posaconazole with other antifungal agents may be synergistic. Hence, posaconazole is a potential candidate as a single or combination agent for difficult-to-treat fungal infections. Posaconazole has an excellent safety profile; to date, serious side effects are rare, even with prolonged use. However, newer posaconazole formulations achieve higher blood levels and it remains to be seen whether this may lead to an increase in the rate of adverse effects. Currently, posaconazole is used predominantly

  20. Bacterial and fungal keratitis in Upper Egypt: In vitro screening of enzymes, toxins and antifungal activity

    PubMed Central

    Gharamah, Abdullah A; Moharram, Ahmed M; Ismail, Mady A; AL-Hussaini, Ashraf K

    2014-01-01

    Purpose: This work was conducted to study the ability of bacterial and fungal isolates from keratitis cases in Upper Egypt to produce enzymes, toxins, and to test the isolated fungal species sensitivity to some therapeutic agents. Materials and Methods: One hundred and fifteen patients clinically diagnosed to have microbial keratitis were investigated. From these cases, 37 bacterial isolates and 25 fungal isolates were screened for their ability to produce extra-cellular enzymes in solid media. In addition, the ability of fungal isolates to produce mycotoxins and their sensitivity to 4 antifungal agents were tested. Results: Protease, lipase, hemolysins, urease, phosphatase, and catalase were detected respectively in 48.65%, 37.84%, 59.46%, 43.24%, 67.57%, and 100% out of 37 bacterial isolates tested. Out of 25 fungal isolates tested during the present study, 80% were positive for protease, 84% for lipase and urease, 28% for blood hemolysis, and 100% for phosphatase and catalase enzymes. Thirteen fungal isolates were able to produce detectable amounts of 7 mycotoxins in culture medium (aflatoxins (B1, B2, G1, and G2), sterigmatocystin, fumagillin, diacetoxyscirpenol, zearalenone, T-2 toxin, and trichodermin). Among the antifungal agents tested in this study, terbinafine showed the highest effect against most isolates in vitro. Conclusion: In conclusion, the ability of bacterial and fungal isolates to produce extracellular enzymes and toxins may be aid in the invasion and destruction of eye tissues, which, in turn, lead to vision loss. PMID:24008795

  1. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  2. Granule-Dependent Natural Killer Cell Cytotoxicity to Fungal Pathogens

    PubMed Central

    Ogbomo, Henry; Mody, Christopher H.

    2017-01-01

    Natural killer (NK) cells kill or inhibit the growth of a number of fungi including Cryptococcus, Candida, Aspergillus, Rhizopus, and Paracoccidioides. Although many fungi are not dangerous, invasive fungal pathogens, such as Cryptococcus neoformans, cause life-threatening disease in individuals with impaired cell-mediated immunity. While there are similarities to cell-mediated killing of tumor cells, there are also important differences. Similar to tumor killing, NK cells directly kill fungi in a receptor-mediated and cytotoxic granule-dependent manner. Unlike tumor cell killing where multiple NK cell-activating receptors cooperate and signal events that mediate cytotoxicity, only the NKp30 receptor has been described to mediate signaling events that trigger the NK cell to mobilize its cytolytic payload to the site of interaction with C. neoformans and Candida albicans, subsequently leading to granule exocytosis and fungal killing. More recently, the NKp46 receptor was reported to bind Candida glabrata adhesins Epa1, 6, and 7 and directly mediate fungal clearance. A number of unanswered questions remain. For example, is only one NK cell-activating receptor sufficient for signaling leading to fungal killing? Are the signaling pathways activated by fungi similar to those activated by tumor cells during NK cell killing? How do the cytolytic granules traffic to the site of interaction with fungi, and how does this process compare with tumor killing? Recent insights into receptor use, intracellular signaling and cytolytic granule trafficking during NK cell-mediated fungal killing will be compared to tumor killing, and the implications for therapeutic approaches will be discussed. PMID:28123389

  3. [symbol: see text]Caspofungin and [symbol: see text]voriconazole for fungal infections.

    PubMed

    2004-01-01

    Systemic fungal infections are difficult to treat and often fatal. Established treatment options include conventional amphotericin B or one of its lipid-based or liposomal formulations, or a triazole antifungal such as fluconazole or itraconazole. [symbol: see text]Caspofungin (Cancidas--Merck Sharp & Dohme) and [symbol: see text]voriconazole (Vfend--Pfizer) are two new antifungals for severe infections caused by Candida spp. (invasive candidiasis) and Aspergillus spp. (invasive aspergillosis). Caspofungin is the first licensed echinocandin antifungal, while voriconazole is a triazole. Promotional claims for caspofungin include that it "provides an effective, yet less toxic, alternative to amphotericin B" while voriconazole is claimed to offer "significantly improved survival in invasive aspergillosis compared with amphotericin B". Here we consider the place of caspofungin and voriconazole in managing patients with severe fungal infections.

  4. Severity of Acute Respiratory Distress Syndrome in haematology patients: long-term impact and early predictive factors.

    PubMed

    Lagier, D; Platon, L; Chow-Chine, L; Sannini, A; Bisbal, M; Brun, J-P; Blache, J-L; Faucher, M; Mokart, D

    2016-09-01

    Severe forms of acute respiratory distress syndrome in patients with haematological diseases expose clinicians to specific medical and ethical considerations. We prospectively followed 143 patients with haematological malignancies, and whose lungs were mechanically ventilated for more than 24 h, over a 5-y period. We sought to identify prognostic factors of long-term outcome, and in particular to evaluate the impact of the severity of acute respiratory distress syndrome in these patients. A secondary objective was to identify the early (first 48 h from ICU admission) predictive factors for acute respiratory distress syndrome severity. An evolutive haematological disease (HR 1.71; 95% CI 1.13-2.58), moderate to severe acute respiratory distress syndrome (HR 1.81; 95% CI 1.13-2.69) and need for renal replacement therapy (HR 2.24; 95% CI 1.52-3.31) were associated with long-term mortality. Resolution of neutropaenia during ICU stay (HR 0.63; 95% CI 0.42-0.94) and early microbiological documentation (HR 0.62; 95% CI 0.42-0.91) were associated with survival. The extent of pulmonary infiltration observed on the first chest X-ray and the diagnosis of invasive fungal infection were the most relevant early predictive factors of the severity of acute respiratory distress syndrome.

  5. Ecology of Fungal Plant Pathogens.

    PubMed

    Termorshuizen, Aad J

    2016-12-01

    Fungal plant pathogens are ubiquitous and highly diverse. Key to their success is high host density, which notably is the case in agroecosystems. Several hypotheses related to the effects of plant pathogens on plant diversity (the Janzen-Connell hypothesis, the dilution effect hypothesis) and the phenomenon of higher biomass in plant mixtures (i.e., overyielding) can all be explained by the quantitative interplay between host and pathogen density. In many agroecosystems, fungal plant pathogens cause great losses, since in monocultures diseased plants cannot be replaced by healthy plants. On the other hand, in natural ecosystems fungal plant pathogens shape the succession of vegetation and enhance the biodiversity of forests and grasslands. When pathogens are introduced into areas outside their natural range, they may behave differently, causing severe damage. Once introduced, changes may occur such as hybridization with other closely related pathogens or host shifts, host jumps, or horizontal gene transfer. Such changes can be hazardous for both agricultural and natural ecosystems.

  6. Four cats with fungal rhinitis.

    PubMed

    Whitney, Beth L; Broussard, John; Stefanacci, Joseph D

    2005-02-01

    Fungal rhinitis is uncommon in the cat and cases of nasal aspergillosis-penicilliosis have been rarely reported. Signs of fungal rhinitis include epistaxis, sneezing, mucopurulent nasal discharge and exophthalmos. Brachycephalic feline breeds seem to be at increased risk for development of nasal aspergillosis-penicilliosis. Computed tomography (CT) imaging and rhinoscopy are useful in assessing the extent of the disease and in obtaining diagnostic samples. Fungal culture may lead to false negative or positive results and must be used in conjunction with other diagnostic tests. Serological testing was not useful in two cats tested. The cats in this study were treated with oral itraconazole therapy. When itraconazole therapy was discontinued prematurely, clinical signs recurred. Hepatotoxicosis is a possible sequel to itraconazole therapy.

  7. Fungal infection following renal transplantation.

    PubMed

    Gallis, H A; Berman, R A; Cate, T R; Hamilton, J D; Gunnells, J C; Stickel, D L

    1975-09-01

    Twenty-seven deep fungal infections developed in 22 of 171 patients following renal transplantation. These infections included cryptococcosis (ten), nocardiosis (seven), candidiasis (four), aspergillosis (two), phycomycosis (two), chromomycosis (one), and subcutaneous infection with Phialophora gougeroti (one). Twelve infections occurred in living-related and ten in cadaveric recipients. Nineteen of the 22 patients were male. Infections occurred from 0 to 61 months after transplantation. Complicating non-fungal infections were present concomitantly in 15 patients. Thirteen patients died, eight probably as a result of fungal infection. Appropriate diagnostic procedures yielded a diagnosis in 20 of 27 infections, and therapy was begun in 18 patients. Serologic, culture, and biopsy procedures useful in making rapid diagnoses are advocated in the hope of increasing survival.

  8. The Fungal Defensin Family Enlarged

    PubMed Central

    Wu, Jiajia; Gao, Bin; Zhu, Shunyi

    2014-01-01

    Fungi are an emerging source of peptide antibiotics. With the availability of a large number of model fungal genome sequences, we can expect that more and more fungal defensin-like peptides (fDLPs) will be discovered by sequence similarity search. Here, we report a total of 69 new fDLPs encoded by 63 genes, in which a group of fDLPs derived from dermatophytes are defined as a new family (fDEF8) according to sequence and phylogenetic analyses. In the oleaginous fungus Mortierella alpine, fDLPs have undergone extensive gene expansion. Our work further enlarges the fungal defensin family and will help characterize new peptide antibiotics with therapeutic potential. PMID:25230677

  9. Positive feedback between mycorrhizal fungi and plants influences plant invasion success and resistance to invasion.

    PubMed

    Zhang, Qian; Yang, Ruyi; Tang, Jianjun; Yang, Haishui; Hu, Shuijin; Chen, Xin

    2010-08-24

    Negative or positive feedback between arbuscular mycorrhizal fungi (AMF) and host plants can contribute to plant species interactions, but how this feedback affects plant invasion or resistance to invasion is not well known. Here we tested how alterations in AMF community induced by an invasive plant species generate feedback to the invasive plant itself and affect subsequent interactions between the invasive species and its native neighbors. We first examined the effects of the invasive forb Solidago canadensis L. on AMF communities comprising five different AMF species. We then examined the effects of the altered AMF community on mutualisms formed with the native legume forb species Kummerowia striata (Thunb.) Schindl. and on the interaction between the invasive and native plants. The host preferences of the five AMF were also assessed to test whether the AMF form preferred mutualistic relations with the invasive and/or the native species. We found that S. canadensis altered AMF spore composition by increasing one AMF species (Glomus geosporum) while reducing Glomus mosseae, which is the dominant species in the field. The host preference test showed that S. canadensis had promoted the abundance of AMF species (G. geosporum) that most promoted its own growth. As a consequence, the altered AMF community enhanced the competitiveness of invasive S. canadensis at the expense of K. striata. Our results demonstrate that the invasive S. canadensis alters soil AMF community composition because of fungal-host preference. This change in the composition of the AMF community generates positive feedback to the invasive S. canadensis itself and decreases AM associations with native K. striata, thereby making the native K. striata less dominant.

  10. Emergence and accumulation of novel pathogens suppress an invasive species.

    PubMed

    Stricker, Kerry Bohl; Harmon, Philip F; Goss, Erica M; Clay, Keith; Luke Flory, S

    2016-04-01

    Emerging pathogens are a growing threat to human health, agriculture and the diversity of ecological communities but may also help control problematic species. Here we investigated the diversity, distribution and consequences of emerging fungal pathogens infecting an aggressive invasive grass that is rapidly colonising habitats throughout the eastern USA. We document the recent emergence and accumulation over time of diverse pathogens that are members of a single fungal genus and represent multiple, recently described or undescribed species. We also show that experimental suppression of these pathogens increased host performance in the field, demonstrating the negative effects of emerging pathogens on invasive plants. Our results suggest that invasive species can facilitate pathogen emergence and amplification, raising concerns about movement of pathogens among agricultural, horticultural, and wild grasses. However, one possible benefit of pathogen accumulation is suppression of aggressive invaders over the long term, potentially abating their negative impacts on native communities.

  11. Pulmonary mucormycosis with embolism: two autopsied cases of acute myeloid leukemia.

    PubMed

    Kogure, Yasunori; Nakamura, Fumihiko; Shinozaki-Ushiku, Aya; Watanabe, Akira; Kamei, Katsuhiko; Yoshizato, Tetsuichi; Nannya, Yasuhito; Fukayama, Masashi; Kurokawa, Mineo

    2014-01-01

    Mucormycosis is an increasingly important cause of morbidity and mortality for patients with hematological malignancies. The diagnosis of mucormycosis usually requires mycological evidence through tissue biopsy or autopsy because the signs and symptoms are nonspecific and there are currently no biomarkers to identify the disease. We herein present two autopsied cases of acute myeloid leukemia with prolonged neutropenia who developed invasive mucormycosis accompanied by pulmonary artery embolism. Our cases were featured by unexplained fever and rapidly progressive dyspnea. Computed tomography scan detected nodular lesions or nonspecific consolidations in the lungs. Cultures, cytological study, and serum fungal markers consistently gave negative results. Autopsy revealed embolism of the pulmonary artery which consisted of fibrin clots by filamentous fungi. Genomic DNA was extracted from the paraffin-embedded clots and was applied to polymerase chain reaction amplification, leading to the diagnosis of infection by Rhizopus microsporus. We should carefully search for life-threatening pulmonary embolism when patients with hematological malignancies develop pulmonary mucormycosis.

  12. Infrared spectroscopy detection of fungal infections and mycotoxins for food safety concerns

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycotoxins, which are toxins produced by fungi, can pose great danger to human health with their acute and chronic effects when contaminated foods (grains, fruits, meat, or milk) are ingested. Fungal infections in food crops are extremely common and many developed countries have set standards to mon...

  13. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  14. Protective immune responses to fungal infections.

    PubMed

    Rivera, A

    2014-09-01

    The incidence of fungal infections has been on the rise over several decades. Fungal infections threaten animals, plants and humans alike and are thus of significant concern to scientists across disciplines. Over the last decade, significant advances on fungal immunology have lead to a better understanding of important mechanisms of host protection against fungi. In this article, I review recent advances of relevant mechanisms of immune-mediated protection to fungal infections.

  15. Skin ph variations from the acute phase to re-epithelialization in burn patients treated with new materials (burnshield®, semipermeable adhesive film, dermasilk®, and hyalomatrix®). Non-invasive preliminary experimental clinical trial.

    PubMed

    Osti, E

    2008-06-30

    The aim of this trial was to measure the pH value of the skin of burn patients using a non-invasive method, from the acute phase through to complete re-epithelialization. The research was then completed by treating the patients with new materials and innovative methods to verify whether this had an effect on the skin pH and on re-epithelialization time. In this clinical trial, the patients were medicated repeatedly with hydrogel (Burnshield®) kept in place by a transparent, semipermeable adhesive film with a moisture vapour transmission rate equivalent to 1600 until day 5 or 6 post-burn. In one patient, treated silk (DermaSilk®) was applied several times until re-epithelialization; in another patient, synthetic hyaluronic acid (Hyalomatrix®) was applied. Various studies using Dermasilk® have confirmed that the fibroin in silk stimulates re-epithelialization, in addition to keeping the burned skin disinfected, thanks to the antimicrobial agent contained in the treated silk. Hyalomatrix® was used on the other patient, as in other studies, as a temporary substitute for the skin in deep burns. Late complications (keloids and hypertrophic scars) can give rise, even after prolonged periods of time, to Marjolin's ulcer (carcinoma but also melanoma and sarcoma), which can develop in the course of a year. A recent Danish trial affirms that appropriate burn treatment facilitates re-epithelialization and decreases the incidence of Marjolin's ulcer. For the trial, we used a centimetre-wide strip of reactive paper sensitive to pH variations and an acid test (Duotest® kit) as a reference, applied for more than one minute on the patient's burned and slightly damp skin. We performed control procedures on the patient's normal skin, away from the wound site. The pH was measured from day 1 post-burn and every other day thereafter until complete re-epithelialization. We found alkaline pH values for the burned skin from the day of the burn until day 12, with an alkaline pH peak

  16. Loss of functional diversity and network modularity in introduced plant-fungal symbioses.

    PubMed

    Dickie, Ian A; Cooper, Jerry A; Bufford, Jennifer L; Hulme, Philip E; Bates, Scott T

    2016-12-30

    The introduction of alien plants into a new range can result in the loss of co-evolved symbiotic organisms, such as mycorrhizal fungi, that are essential for normal plant physiological functions. Prior studies of mycorrhizal associations in alien plants have tended to focus on individual plant species on a case-by-case basis. This approach limits broad scale understanding of functional shifts and changes in interaction network structure that may occur following introduction. Here we use two extensive datasets of plant-fungal interactions derived from fungal sporocarp observations and recorded plant hosts in two island archipelago nations: New Zealand (NZ) and the United Kingdom (UK). We found that the NZ dataset shows a lower functional diversity of fungal hyphal foraging strategies in mycorrhiza of alien as compared with native trees. Across species this resulted in fungal foraging strategies associated with alien trees being much more variable in functional composition compared with native trees, which had a strikingly similar functional composition. The UK data showed no functional difference in fungal associates of alien and native plant genera. Notwithstanding this, both the NZ and UK data showed a substantial difference in interaction network structure of alien trees compared with native trees. In both cases, fungal associates of native trees showed strong modularity, while fungal associates of alien trees generally integrated into a single large module. The results suggest a lower functional diversity (in one dataset) and a simplification of network structure (in both) as a result of introduction, potentially driven by either limited symbiont co-introductions or disruption of habitat as a driver of specificity due to nursery conditions, planting, or plant edaphic-niche expansion. Recognizing these shifts in function and network structure has important implications for plant invasions and facilitation of secondary invasions via shared mutualist populations.

  17. Fungal endophyte diversity in Sarracenia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal endophytes were isolated from four species of the carnivorous pitcher plant genus Sarracenia: S. minor, S. oreophila, S. purpurea, and S. psittacina. Twelve taxa of fungi, eight within the Ascomycota and four within the Basidiomycota, were identified based on PCR amplification and sequencing ...

  18. DEMONSTRATION BULLETIN: FUNGAL TREATMENT BULLETIN

    EPA Science Inventory

    Fungal treatment technology uses white rot fungi (lignin degrading fungi) to treat organic contaminated soils in situ. Organic materials inoculated with the fungi are mechanically mixed into the contaminated soil. Using enzymes normally produced for wood degradation as well as ot...

  19. Esophagectomy - minimally invasive

    MedlinePlus

    Minimally invasive esophagectomy; Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the ...

  20. Novel Disease Susceptibility Factors for Fungal Necrotrophic Pathogens in Arabidopsis

    PubMed Central

    García-Andrade, Javier; Angulo, Carlos; Neumetzler, Lutz; Persson, Staffan; Vera, Pablo

    2015-01-01

    Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors (TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR (for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens. PMID:25830627

  1. Fungal isolation and enumeration in foods.

    PubMed

    Bueno, Dante Javier; Silva, Julio Oscar; Oliver, Guillermo

    2004-01-01

    Humans have now been growing and storing enough food for a long enough time that some rapidly evolving organisms, such as fungi, are moving into niches created by the exploitation of certain plants as food. Food is expected to be nutritious. The most important of the physicochemical conditions that affects fungal growth is related to the biological state of the food. Living foods, particularly fresh fruits, vegetables, and also grains and nuts before harvest, possess powerful defense mechanisms against microbial invasion. When the specific microorganisms overcome defense mechanisms, the spoilage of a living food starts. Other factors to consider are water activity, hydrogen ion concentration, temperature, gas tension, consistency, nutrient status, specific solute effect, and preservation. The consequences of mold contamination of foods are diverse: unsightly appearance, chemical (removal or change of most of the constituents) and nutritional value changes, modification of organoleptic quality, difficulties in preservation, occupational hazards (mycoses, allergies), and toxicoses (mycotoxicoses). It is possible to recognize a succession of three distinct mycoflora during the storage of cereals, but they can also be mixed: 1. Field fungi growing and established before harvesting (Alternaria, Fusarium, Helminthosporium, Cladosporium). 2. Storage fungi taking over and dominanting in the silo (Aspergillus and Penicillium). 3. Advanced decay fungi (Papulospora, Sordaria, Fusarium graminearum, and members of the order Mucorales).

  2. Subseafloor basalts as fungal habitats

    NASA Astrophysics Data System (ADS)

    Ivarsson, M.

    2012-09-01

    The oceanic crust is believed to host the largest potential habitat for microbial life on Earth, yet, still we lack substantial information about the abundance, diversity, and consequence of its biosphere. The last two decades have involved major research accomplishments within this field and a change in view of the ocean crust and its potential to harbour life. Here fossilised fungal colonies in subseafloor basalts are reported from three different seamounts in the Pacific Ocean. The fungal colonies consist of various characteristic structures interpreted as fungal hyphae, fruit bodies and spores. The fungal hyphae are well preserved with morphological characteristics such as hyphal walls, septa, thallic conidiogenesis, and hyphal tips with hyphal vesicles within. The fruit bodies consist of large (∼50-200 µm in diameter) body-like structures with a defined outer membrane and an interior filled with calcite. The fruit bodies have at some stage been emptied of their contents of spores and filled by carbonate-forming fluids. A few fruit bodies not filled by calcite and with spores still within support this interpretation. Spore-like structures (ranging from a few µm to ∼20 µm in diameter) are also observed outside of the fruit bodies and in some cases concentrated to openings in the membrane of the fruit bodies. The hyphae, fruit bodies and spores are all closely associated with a crust lining the vein walls that probably represent a mineralized biofilm. The results support a fungal presence in deep subseafloor basalts and indicate that such habitats were vital between ∼81 and 48 Ma.

  3. Detection of fungal development in closed spaces through the determination of specific chemical targets.

    PubMed

    Moularat, Stéphane; Robine, Enric; Ramalho, Olivier; Oturan, Mehmet A

    2008-05-01

    In addition to the biodegradation problems encountered in buildings, exposure of their occupants to moulds is responsible for numerous diseases: infections (invasive nosocomial aspergillosis), immediate or delayed allergies, food-borne infections and different types of irritation. In this context, the aim of our work has been to determine specific chemical tracers for fungal development on construction materials. More generally, by detecting a specific chemical fingerprint of fungal development, our objective was to propose a microbiological alert system which could control systems and/or procedures for the microbiological treatment of indoor areas. We therefore characterized the chemical emissions from six types of construction material contaminated artificially by moulds. Chemical fingerprints were established for 19 compounds arising specifically from fungal metabolism: 2-ethylhexanoic acid methyl ester, 1-octen-3-ol, 3-heptanol, 3-methyl-1-butanol, 2-methyl-1-butanol, 1,3-octadiene, 2-(5H)-furanone, 2-heptene, alpha-pinene, 2-methylisoborneol, 4-heptanone, 2-methylfuran, 3-methylfuran, dimethyldisulfide, methoxybenzene, a terpenoid and three sesquiterpenes. Determining the origin of these compounds and their specific links with a growth substrate or fungal species made it possible to judge the pertinence of choosing these compounds as tracers. Thus the detecting specific volatile organic compounds emitted as from the second day of fungal growth demonstrated that this approach had the advantage of detecting fungal development both reliably and rapidly before any visible signs of contamination could be detected.

  4. The Chemical Basis of Fungal Bioluminescence.

    PubMed

    Purtov, Konstantin V; Petushkov, Valentin N; Baranov, Mikhail S; Mineev, Konstantin S; Rodionova, Natalja S; Kaskova, Zinaida M; Tsarkova, Aleksandra S; Petunin, Alexei I; Bondar, Vladimir S; Rodicheva, Emma K; Medvedeva, Svetlana E; Oba, Yuichi; Oba, Yumiko; Arseniev, Alexander S; Lukyanov, Sergey; Gitelson, Josef I; Yampolsky, Ilia V

    2015-07-06

    Many species of fungi naturally produce light, a phenomenon known as bioluminescence, however, the fungal substrates used in the chemical reactions that produce light have not been reported. We identified the fungal compound luciferin 3-hydroxyhispidin, which is biosynthesized by oxidation of the precursor hispidin, a known fungal and plant secondary metabolite. The fungal luciferin does not share structural similarity with the other eight known luciferins. Furthermore, it was shown that 3-hydroxyhispidin leads to bioluminescence in extracts from four diverse genera of luminous fungi, thus suggesting a common biochemical mechanism for fungal bioluminescence.

  5. Successful treatment of gastrointestinal mucormycosis in an adult with acute leukemia: case report and literature review

    PubMed Central

    Alghamdi, A.; Lutynski, A.; Minden, M.; Rotstein, C.

    2017-01-01

    Mucormycosis has emerged as an important cause of invasive fungal infection in patients with hematologic malignancies. Gastrointestinal mucormycosis is an unusual presentation of this invasive fungal infection, and it causes considerable morbidity and mortality. Such outcomes are due in part to a nonspecific presentation that results in delays in diagnosis and treatment. Successful treatment of gastrointestinal mucormycosis involves surgical debridement and appropriate antifungal therapy. PMID:28270734

  6. Fungal exopolysaccharide: production, composition and applications.

    PubMed

    Mahapatra, Subhadip; Banerjee, Debdulal

    2013-01-01

    Fungal exopolysaccharides (EPSs) have been recognized as high value biomacromolecules for the last two decades. These products, including pullulan, scleroglucan, and botryosphaeran, have several applications in industries, pharmaceuticals, medicine, foods etc. Although fungal EPSs are highly relevant, to date information concerning fungal biosynthesis is scarce and an extensive search for new fugal species that can produce novel EPSs is still needed. In most cases, the molecular weight variations and sugar compositions of fungal EPSs are dependent to culture medium composition and different physical conditions provided during fermentation. An inclusive and illustrative review on fungal EPS is presented here. The general outline of the present work includes fungal EPS production, their compositions and applications. An emphasis is also given to listing out different fungal strains that can produce EPSs.

  7. Fungal Exopolysaccharide: Production, Composition and Applications

    PubMed Central

    Mahapatra, Subhadip; Banerjee, Debdulal

    2013-01-01

    Fungal exopolysaccharides (EPSs) have been recognized as high value biomacromolecules for the last two decades. These products, including pullulan, scleroglucan, and botryosphaeran, have several applications in industries, pharmaceuticals, medicine, foods etc. Although fungal EPSs are highly relevant, to date information concerning fungal biosynthesis is scarce and an extensive search for new fugal species that can produce novel EPSs is still needed. In most cases, the molecular weight variations and sugar compositions of fungal EPSs are dependent to culture medium composition and different physical conditions provided during fermentation. An inclusive and illustrative review on fungal EPS is presented here. The general outline of the present work includes fungal EPS production, their compositions and applications. An emphasis is also given to listing out different fungal strains that can produce EPSs. PMID:24826070

  8. [Combination therapy for invasive aspergillosis].

    PubMed

    Ruiz-Camps, Isabel

    2011-03-01

    The frequency of invasive fungal infections, and specifically invasive aspergillosis, has increased in the last few decades. Despite the development of new antifungal agents, these infections are associated with high mortality, ranging from 40% to 80%, depending on the patient and the localization of the infection. To reduce these figures, several therapeutic strategies have been proposed, including combination therapy. Most of the available data on the efficacy of these combinations are from experimental models, in vitro data and retrospective observational studies or studies with a small number of patients that have included both patients in first-line treatment and those receiving rescue therapy; in addition there are many patients with possible forms of aspergillosis and few with demonstrated or probable forms. To date, there is no evidence that combination therapy has significantly higher efficacy than monotherapy; however, combination therapy could be indicated in severe forms of aspergillosis, or forms with central nervous involvement or extensive pulmonary involvement with respiratory insufficiency, etc. Among the combinations, the association of an echinocandin--the group that includes micafungin--with voriconazole or liposomal amphotericin B seems to show synergy. These combinations are those most extensively studied in clinical trials and therefore, although the grade of evidence is low, are recommended by the various scientific societies.

  9. Automated image-based analysis of spatio-temporal fungal dynamics.

    PubMed

    Vidal-Diez de Ulzurrun, G; Baetens, J M; Van den Bulcke, J; Lopez-Molina, C; De Windt, I; De Baets, B

    2015-11-01

    Due to their ability to grow in complex environments, fungi play an important role in most ecosystems and have for that reason been the subject of numerous studies. Some of the main obstacles to the study of fungal growth are the heterogeneity of growth environments and the limited scope of laboratory experiments. Given the increasing availability of image capturing techniques, a new approach lies in image analysis. Most previous image analysis studies involve manual labelling of the fungal network, tracking of individual hyphae, or invasive techniques that do not allow for tracking the evolution of the entire fungal network. In response, this work presents a highly versatile tool combining image analysis and graph theory to monitor fungal growth through time and space for different fungal species and image resolutions. In addition, a new experimental set-up is presented that allows for a functional description of fungal growth dynamics and a quantitative mutual comparison of different growth behaviors. The presented method is completely automated and facilitates the extraction of the most studied fungal growth features such as the total length of the mycelium, the area of the mycelium and the fractal dimension. The compactness of the fungal network can also be monitored over time by computing measures such as the number of tips, the node degree and the number of nodes. Finally, the average growth angle and the internodal length can be extracted to study the morphology of the fungi. In summary, the introduced method offers an updated and broader alternative to classical and narrowly focused approaches, thus opening new avenues of investigation in the field of mycology.

  10. Fungal Endophyte Diversity in Sarracenia

    PubMed Central

    Glenn, Anthony; Bodri, Michael S.

    2012-01-01

    Fungal endophytes were isolated from 4 species of the carnivorous pitcher plant genus Sarracenia: S. minor, S. oreophila, S. purpurea, and S. psittacina. Twelve taxa of fungi, 8 within the Ascomycota and 4 within the Basidiomycota, were identified based on PCR amplification and sequencing of the internal transcribed spacer sequences of nuclear ribosomal DNA (ITS rDNA) with taxonomic identity assigned using the NCBI nucleotide megablast search tool. Endophytes are known to produce a large number of metabolites, some of which may contribute to the protection and survival of the host. We speculate that endophyte-infected Sarracenia may benefit from their fungal associates by their influence on nutrient availability from within pitchers and, possibly, by directly influencing the biota within pitchers. PMID:22427921

  11. Structural aspects of fungal allergens.

    PubMed

    Crameri, Reto

    2015-03-01

    Despite the increasing number of solved crystal structures of allergens, the key question why some proteins are allergenic and the vast majority is not remains unanswered. The situation is not different for fungal allergens which cover a wide variety of proteins with different chemical properties and biological functions. They cover enzymes, cell wall, secreted, and intracellular proteins which, except cross-reactive allergens, does not show any evidence for structural similarities at least at the three-dimensional level. However, from a diagnostic point of view, pure allergens biotechnologically produced by recombinant technology can provide us, in contrast to fungal extracts which are hardly producible as standardized reagents, with highly pure perfectly standardized diagnostic reagents.

  12. Insights Regarding Fungal Phosphoproteomic Analysis.

    PubMed

    Ribeiro, Liliane F C; Chelius, Cynthia L; Harris, Steven D; Marten, Mark R

    2017-03-10

    Protein phosphorylation is a major means of regulation for cellular processes, and is important in cell signaling, growth, and cell proliferation. To study phosphorylated proteins, high throughput phosphoproteomic technologies, such as reverse phase protein array, phospho-specific flow cytometry, and mass spectrometry (MS) based technologies, have been developed. Among them, mass spectrometry has become the primary tool employed for the identification of phosphoproteins and phosphosites in fungi, leading to an improved understanding of a number of signaling pathways. Using mass spectrometry techniques, researchers have discovered new kinase substrates, established connections between kinases and fungal pathogenicity, and studied the evolutionary lineage of kinases between different fungal species. Further, many specific phosphorylation sites recognized by individual kinases have been described. In this review, we will focus on recent discoveries made in yeast and filamentous fungi using phosphoproteomic analysis.

  13. Fungal metabolites with anticancer activity.

    PubMed

    Evidente, Antonio; Kornienko, Alexander; Cimmino, Alessio; Andolfi, Anna; Lefranc, Florence; Mathieu, Véronique; Kiss, Robert

    2014-05-01

    Covering: 1964 to 2013. Natural products from bacteria and plants have played a leading role in cancer drug discovery resulting in a large number of clinically useful agents. In contrast, the investigations of fungal metabolites and their derivatives have not led to a clinical cancer drug in spite of significant research efforts revealing a large number of fungi-derived natural products with promising anticancer activity. Many of these natural products have displayed notable in vitro growth-inhibitory properties in human cancer cell lines and select compounds have been demonstrated to provide therapeutic benefits in mouse models of human cancer. Many of these compounds are expected to enter human clinical trials in the near future. The present review discusses the reported sources, structures and biochemical studies aimed at the elucidation of the anticancer potential of these promising fungal metabolites.

  14. Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion

    PubMed Central

    Tenor, Jennifer L.; Oehlers, Stefan H.; Yang, Jialu L.

    2015-01-01

    ABSTRACT The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of Cryptococcus with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel of Cryptococcus mutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals that C. neoformans is able to penetrate the zebrafish brain following intravenous infection. By studying a C. neoformans FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-C. neoformans platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents. PMID:26419880

  15. Subseafloor basalts as fungal habitats

    NASA Astrophysics Data System (ADS)

    Ivarsson, M.; Bengtson, S.

    2013-12-01

    The oceanic crust makes up the largest potential habitat for life on Earth, yet next to nothing is known about the abundance, diversity and ecology of its biosphere. Our understanding of the deep biosphere of subseafloor crust is, with a few exceptions, based on a fossil record. Surprisingly, a majority of the fossilized microorganisms have been interpreted or recently re-interpreted as remnants of fungi rather than prokaryotes. Even though this might be due to a bias in fossilization the presence of fungi in these settings can not be neglected. We have examined fossilized microorganisms in drilled basalt samples collected at the Emperor Seamounts in the Pacific Ocean. Synchrotron-radiation X-ray tomography microscopy (SRXTM) studies has revealed a complex morphology and internal structure that corresponds to characteristic fungal morphology. Chitin was detected in the fossilized hyphae, which is another strong argument in favour of a fungal interpretation. Chitin is absent in prokaryotes but a substantial constituent in fungal cell walls. The fungal colonies consist of both hyphae and yeast-like growth states as well as resting structures and possible fruit bodies, thus, the fungi exist in vital colonies in subseafloor basalts. The fungi have also been involved in extensive weathering of secondary mineralisations. In terrestrial environments fungi are known as an important geobiological agent that promotes mineral weathering and decomposition of organic matter, and they occur in vital symbiosis with other microorganisms. It is probable to assume that fungi would play a similar role in subseafloor basalts and have great impact on the ecology and on biogeochemical cycles in such environments.

  16. Subcutaneous Fungal Cyst Masquerading as Benign Lesions – A Series of Eight Cases

    PubMed Central

    Varghese, Renu G’Boy; Phansalkar, Manjiri; Ramdas, Anita; K, Authy; G, Thangiah

    2015-01-01

    Background Subcutaneous fungal infections are caused by penetration of the causative fungi into the subcutaneous layer and are usually localised. We present a series of eight cases with subcutaneous fungal cystic lesions masquerading as benign lesions. Materials and Methods A retrospective study was conducted on subcutaneous fungal infections seen between January 2007 to July 2014 in the Department of Pathology. Eight patients with biopsy proven subcutaneous fungal infection were included. We collected and analysed their demographic, clinical and histopathological details. Results Among eight patients, six were male and two were female. The mean age was 47 years (Range: 21-70). All the eight patients presented with non-tender cystic swelling. The size of the swellings varied from a minimum of 3x3 cm to maximum of 10x4 cm. Out of eight, hand was involved in three, forearm in one, elbow in two, leg in one and foot in one. On H&E staining, all the cases showed fibro collagenous cyst wall, lined by histiocytes, granulomatous reaction, foreign body type of giant cells with acute and chronic inflammatory infiltrate containing fungal elements. Six were identified as hyalohyphomycosis and two were identified as phaeohyphomycotic cysts based on pigmentation of hyphae. Conclusion Fungal infection should be suspected in all subcutaneous cystic lesions. Excised tissue should always be sent for culture and histopathology. PMID:26557537

  17. Fungal genome resources at NCBI.

    PubMed

    Robbertse, B; Tatusova, T

    2011-09-01

    The National Center for Biotechnology Information (NCBI) is well known for the nucleotide sequence archive, GenBank and sequence analysis tool BLAST. However, NCBI integrates many types of biomolecular data from variety of sources and makes it available to the scientific community as interactive web resources as well as organized releases of bulk data. These tools are available to explore and compare fungal genomes. Searching all databases with Fungi [organism] at http://www.ncbi.nlm.nih.gov/ is the quickest way to find resources of interest with fungal entries. Some tools though are resources specific and can be indirectly accessed from a particular database in the Entrez system. These include graphical viewers and comparative analysis tools such as TaxPlot, TaxMap and UniGene DDD (found via UniGene Homepage). Gene and BioProject pages also serve as portals to external data such as community annotation websites, BioGrid and UniProt. There are many different ways of accessing genomic data at NCBI. Depending on the focus and goal of research projects or the level of interest, a user would select a particular route for accessing genomic databases and resources. This review article describes methods of accessing fungal genome data and provides examples that illustrate the use of analysis tools.

  18. Epidemiology of nosocomial fungal infections.

    PubMed Central

    Fridkin, S K; Jarvis, W R

    1996-01-01

    This paper briefly reviews the current knowledge of the epidemiology and modes of transmission of nosocomial fungal infections and some of the therapeutic options for treating these diseases. In the mid-1980s, many institutions reported that fungi were common pathogens in nosocomial infections. Most, if not all, hospitals care for patients at risk for nosocomial fungal infections. The proportion in all nosocomial infections reportedly caused by Candida spp. increased from 2% in 1980 to 5% in 1986 to 1989. Numerous studies have identified common risk factors for acquiring these infections, most of which are very common among hospitalized patients; some factors act primarily by inducing immunosuppression (e.g., corticosteroids, chemotherapy, malnutrition, malignancy, and neutropenia), while others primarily provide a route of infection (e.g., extensive burns, indwelling catheter), and some act in combination. Non-albicans Candida spp., including fluconazole-resistant C. krusei and Torulopsis (C.) glabrata, have become more common pathogens. Newer molecular typing techniques can assist in the determination of a common source of infection caused by several fungal pathogens. Continued epidemiologic and laboratory research is needed to better characterize these pathogens and allow for improved diagnostic and therapeutic strategies. PMID:8894349

  19. Impact of an Early Invasive Strategy versus Conservative Strategy for Unstable Angina and Non-ST Elevation Acute Coronary Syndrome in Patients with Chronic Kidney Disease: A Systematic Review

    PubMed Central

    Shaw, Catriona; Nitsch, Dorothea; Lee, Jasmine; Fogarty, Damian; Sharpe, Claire C.

    2016-01-01

    Background Clinical practice guidelines support an early invasive approach after NSTE-ACS in patients with chronic kidney disease (CKD). There is no direct randomised controlled trial evidence in the CKD population, and whether the benefit of an early invasive approach is maintained across the spectrum of severity of CKD remains controversial. Methods We conducted a systematic review to evaluate the association between an early invasive approach and all-cause mortality in patients with CKD. We searched MEDLINE and EMBASE (1990-May 2015) and article reference lists. Data describing study design, participants, invasive management strategies, renal function, all-cause mortality and risk of bias were extracted. Results 3,861 potentially relevant studies were identified. Ten studies, representing data on 147,908 individuals with NSTE-ACS met the inclusion criteria. Qualitative heterogeneity in the definitions of early invasive approach, comparison groups and renal dysfunction existed. Meta-analysis of the RCT derived and observational data were generally supportive of an early invasive approach in CKD (RR0.76 (95% CI 0.49–1.17) and RR0.50 (95%CI 0.42–0.59) respectively). Meta-analysis of the observational studies demonstrated a large degree of heterogeneity (I2 79%) driven in part by study size and heterogeneity across various kidney function levels. Conclusions The observational data support that an early invasive approach after NSTE-ACS confers a survival benefit in those with early-moderate CKD. Local opportunities for quality improvement should be sought. Those with severe CKD and the dialysis population are high risk and under-studied. Novel and inclusive approaches for CKD and dialysis patients in cardiovascular clinical trials are needed. PMID:27195786

  20. Application of Bioluminescence Imaging for In Vivo Monitoring of Fungal Infections

    PubMed Central

    Brock, Matthias

    2012-01-01

    Fungi can cause severe invasive infections especially in the immunocompromised host. Patient populations at risk are increasing due to ongoing developments in cancer treatment and transplantation medicine. Only limited diagnostic tools and few antifungals are available, rendering a significant number of invasive fungal infections life threatening. To reduce mortality rates, a better understanding of the infection processes is urgently required. Bioluminescence imaging (BLI) is a powerful tool for such purposes, since it allows visualisation of temporal and spatial progression of infections in real time. BLI has been successfully used to monitor infections caused by various microorganisms, in particular bacteria. However, first studies have also been performed on the fungi Candida albicans and Aspergillus fumigatus. Although BLI was, in principle, suitable to study the infection process, some limitations remained. Here, different luciferase systems are introduced, and current approaches are summarised. Finally, suggestions for further improvements of BLI to monitor fungal infections are provided. PMID:22121368

  1. Sphenoid sinus fungall ball: a retrospective study over a 10- year period.

    PubMed

    Eloy, Ph; Grenier, J; Pirlet, A; Poirrier, A L; Stephens, J S; Rombaux, Ph

    2013-06-01

    A fungal ball consists of a dense conglomerate of fungal hyphae growing at the surface of the sinus mucosa without tissue infiltration. The maxillary sinus is by far the most commonly involved paranasal sinus cavity followed by the sphenoid sinus. The present study is a retrospective study of 25 consecutive cases treated during the last 10 years in the two hospitals be- longing to the Catholic University of Louvain (CHU Mont-Godinne and UCL Saint Luc). We report the symptomatology, the imaging and discuss the different surgical managements. We conclude that the clinician must have a high index of suspicion when dealing with a unilateral rhinosinusitis persisting despite a maximal and well conducted medical treatment. This is particularly so in elderly women when associated with facial pain and post nasal drip, particularly when the computed tomography shows an unilateral opacity of the sphenoid sinus with or without a sclerosis or an erosion of the bony walls, a polyp in the sphenoethmoidal recess or a hyperdensity mimicking a foreign body. An endonasal endoscopic sphenoidotomy is the treatment of choice in most cases, allowing good ventilation of the sinus and radical removal of all the fungal concretion. A biopsy of the sinus mucosa adjacent to fungal elements is of upmost important to confirm the non- invasiveness of the fungi within the tissue. Antifungal medication is not required in uncomplicated forms. All host factors producing some degree of immunosuppression must be corrected when present and must alert the clinician to rule out any forms of invasive disease.

  2. [Fungal infection secondary to treatment of Escherichia coli in a critically ill patient].

    PubMed

    Maack, Kim Hovgaard; Tarp, Britta

    2012-08-27

    The incidence of nosocomial fungal infections has increased over the past 20 years. Candida albicans is the most commonly involved pathogen. Concurrently, the number of non-albicans species with decreased susceptibility to commonly used antifungal agents has increased significantly. Invasive candidiasis is associated with significant morbidity and mortality. We present a case of unusually massive infection with a number of different Candida species, which caused severe prolonged infection in a critically ill patient.

  3. Surgical management of fungal endophthalmitis resulting from fungal keratitis

    PubMed Central

    Gao, Yan; Chen, Nan; Dong, Xiao-Guang; Yuan, Gong-Qiang; Yu, Bin; Xie, Li-Xin

    2016-01-01

    AIM To report the fungal organisms, clinical features, surgical treatment strategies, and outcomes of patients with culture-proven exogenous fungal endophthalmitis (EFE) secondary to keratitis, and evaluate the role of surgery in the treatment. METHODS The clinical records of 27 patients (27 eyes) with culture-proven EFE resulting from fungal keratitis treated at Shandong Eye Institute from January 2007 to January 2015 were retrospectively reviewed. Information about fungal culture results, clinical features, surgical procedures, and final visual acuity was obtained. RESULTS There were 39 positive culture results from samples of cornea, hypopyon, vitreous and lens capsule, accounting for 56%, 26%, 15% and 2.5%, respectively. Fusarium was identified in 44% (12/27) of the eyes, followed by Aspergillus in 22% (6/27). Posterior segment infection was involved in 78% (21/27) of the patients. The corneal infection was larger than 3 mm ×3 mm in 89% (24/27) of the patients, and 22% (6/27) of them had the entire cornea, and even the sclera involved. Three eyes had silicone oil tamponade, and two eyes had retinal detachment. Twenty-two eyes (81.5%) underwent penetrating keratoplasty (PKP), and over half of them (54.5%) were operated within 3d from the onset of antifungal therapy. Fourteen eyes (52%) underwent intracameral antifungal drug injection, and three of them required repeated injections. Fifteen eyes (55.6%) underwent pars plana vitrectomy (PPV). The rate of the eyes undergoing PPV as the initial surgical procedure was 60% (9/15), lower than 77% in PKP. Intravitreal injection was given in 59% of the eyes (16/27), and 75% of them required repeated injections. The final visual acuity was 20/100 or better in 37% of the eyes, and better than counting fingers in 55.6% of the eyes. Five eyes (18.5%) were eviscerated. In the two eyes with concurrent retinal detachment, one achieved retinal reattachment, and the other was eviscerated. In the three eyes with silicone oil

  4. Evaluation of Luminex xTAG fungal analyte-specific reagents for rapid identification of clinically relevant fungi.

    PubMed

    Babady, N Esther; Miranda, Edwin; Gilhuley, Kathleen A

    2011-11-01

    Invasive fungal infections (IFI) remain a serious threat to immunocompromised hosts. Current diagnostic methods, including fungal culture and antigen detection, are slow and often lack specificity. Rapid diagnostic tools with increased sensitivity and specificity could improve the care of patients with IFI. Recently, Luminex Molecular Diagnostics (Toronto, Canada) developed 23 analyte-specific reagents (ASRs) for the detection of the most common clinically relevant fungi. This study's objective was to evaluate the sensitivity and specificity of a subset of these ASRs for fungal isolates and clinical specimens. Previously characterized fungal and bacterial isolates (n = 110), blood culture specimens (n = 34), and respiratory specimens (n = 44) were tested using either a Candida 7-plex panel (Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Candida guilliermondii, and Candida krusei) or a mold 11-plex panel (Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Scedosporium prolificans, Scedosporium apiospermum, Fusarium oxysporum/Fusarium solani, Rhizopus arrhizus, Rhizopus microsporus, Mucor indicus, and Cunninghamella bertholletiae). The Candida 7-plex panel correctly identified all Candida isolates as confirmed by fungal culture and biochemical tests, for a sensitivity and specificity of 100%. The mold 11-plex panel correctly identified all mold isolates tested except for A. niger. Fungal isolates of Rhizopus and Mucor species were not detected, either, although they could represent species other than those targeted by the ASRs. Further evaluation will be necessary to confirm the sensitivities of some of the mold ASRs. Implementation of these ASRs will allow same-day detection of fungal DNA in clinical specimens.

  5. Invasive Mold Infections: Virulence and Pathogenesis of Mucorales

    PubMed Central

    Morace, Giulia; Borghi, Elisa

    2012-01-01

    Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses. PMID:22121366

  6. The Global Burden of Fungal Diseases.

    PubMed

    Vallabhaneni, Snigdha; Mody, Rajal K; Walker, Tiffany; Chiller, Tom

    2016-03-01

    Fungal diseases require greater attention today than ever before, given the expanding population of immunosuppressed patients who are at higher risk for these diseases. This article reports on distribution, incidence, and prevalence of various fungal diseases and points out gaps in knowledge where such data are not available. Fungal diseases that contribute substantially to global morbidity and mortality are highlighted. Long-term, sustainable surveillance programs for fungal diseases and better noninvasive and reliable diagnostic tools are needed to estimate the burden of these diseases more accurately.

  7. Early diagnosis of invasive mould infections and disease.

    PubMed

    Lamoth, Frédéric; Calandra, Thierry

    2017-03-01

    Invasive mould infections (IMIs), such as invasive aspergillosis or mucormycosis, are a major cause of death in patients with haematological cancer and in patients receiving long-term immunosuppressive therapy. Early diagnosis and prompt initiation of antifungal therapy are crucial steps in the management of patients with IMI. The diagnosis of IMI remains a major challenge, with an increased spectrum of fungal pathogens and a diversity of clinical and radiological presentations within the expanding spectrum of immunocompromised hosts. Diagnosis is difficult to establish and is expressed on a scale of probability (proven, probable and possible). Imaging (CT scan), microbiological tools (direct examination, culture, PCR, fungal biomarkers) and histopathology are the pillars of the diagnostic work-up of IMI. None of the currently available diagnostic tests provides sufficient sensitivity and specificity alone, so the optimal approach relies on a combination of multiple diagnostic strategies, including imaging, fungal biomarkers (galactomannan and 1,3-β-d-glucan) and molecular tools. In recent years, the development of PCR for filamentous fungi (primarily Aspergillus or Mucorales) and the progress made in the standardization of fungal PCR technology, may lead to future advances in the field. The appropriate diagnostic approach for IMI should be individualized to each centre, taking into account the local epidemiology of IMI and the availability of diagnostic tests.

  8. Quantification of Fungal DNA by Using Fluorescence Resonance Energy Transfer and the Light Cycler System

    PubMed Central

    Loeffler, Juergen; Henke, Norbert; Hebart, Holger; Schmidt, Diethard; Hagmeyer, Lars; Schumacher, Ulrike; Einsele, Hermann

    2000-01-01

    The Light Cycler technique combines rapid in vitro amplification of DNA in glass capillaries with real-time species determination and quantification of DNA load. We have established a quantitative PCR protocol for two clinically important pathogens, Candida albicans and Aspergillus fumigatus. The sensitivity of the assay was comparable to those of previously described PCR protocols (5 CFU/ml). Specific detection of C. albicans and A. fumigatus could be achieved. The assay showed a high reproducibility of 96 to 99%. The assay was linear in a range between 101 and 104 Aspergillus conidia. As capillaries do not have to be reopened for post-PCR analysis, the risk of carryover contaminations could be minimized. The Light Cycler allowed quantification of the fungal loads in a limited number of clinical specimens from patients with hematological malignancies and histologically proven invasive fungal infections. Five of nine positive samples had fungal loads between 5 and 10 CFU/ml of blood, two of nine positive samples had fungal loads between 10 and 100 CFU/ml of blood, and two of nine samples had fungal loads of more than 100 CFU/ml of blood. All samples were also found to be PCR positive by PCR–enzyme-linked immunosorbent assay analysis. PMID:10655350

  9. Fungal Mimicry of a Mammalian Aminopeptidase Disables Innate Immunity and Promotes Pathogenicity.

    PubMed

    Sterkel, Alana K; Lorenzini, Jenna L; Fites, J Scott; Subramanian Vignesh, Kavitha; Sullivan, Thomas D; Wuthrich, Marcel; Brandhorst, Tristan; Hernandez-Santos, Nydiaris; Deepe, George S; Klein, Bruce S

    2016-03-09

    Systemic fungal infections trigger marked immune-regulatory disturbances, but the mechanisms are poorly understood. We report that the pathogenic yeast of Blastomyces dermatitidis elaborates dipeptidyl-peptidase IVA (DppIVA), a close mimic of the mammalian ectopeptidase CD26, which modulates critical aspects of hematopoiesis. We show that, like the mammalian enzyme, fungal DppIVA cleaved C-C chemokines and GM-CSF. Yeast producing DppIVA crippled the recruitment and differentiation of monocytes and prevented phagocyte activation and ROS production. Silencing fungal DppIVA gene expression curtailed virulence and restored recruitment of CCR2(+) monocytes, generation of TipDC, and phagocyte killing of yeast. Pharmacological blockade of DppIVA restored leukocyte effector functions and stemmed infection, while addition of recombinant DppIVA to gene-silenced yeast enabled them to evade leukocyte defense. Thus, fungal DppIVA mediates immune-regulatory disturbances that underlie invasive fungal disease. These findings reveal a form of molecular piracy by a broadly conserved aminopeptidase during disease pathogenesis.

  10. Topical therapy for fungal infections.

    PubMed

    Kyle, Amber A; Dahl, Mark V

    2004-01-01

    Fungi often infect the skin surface and subsequently invade the stratum corneum to avoid being shed from the skin surface by desquamation. Pharmacologic agents applied to the surface of the skin in the form of creams, lotions, or sprays, readily penetrate into the stratum corneum to kill the fungi (fungicidal agents), or at least render them unable to grow or divide (fungistatic agents). Thus, topical therapies work well to rid the skin of topical fungi and yeasts. Azole drugs such as miconazole, clotrimazole, and ketoconazole are fungistatic, limiting fungal growth but depending on epidermal turnover to shed the still-living fungus from the skin surface. Allylamines and benzylamines such as terbinafine, naftifine, and butenafine are fungicidal, actually killing the fungal organisms. Fungicidal drugs are often preferred over fungistatic drugs for treatment of dermatophytic fungal infections, since treatment times as short as one application daily for 1 week are associated with high cure rates. Furthermore, patients often stop treatments when the skin appears healed, usually after about a week of treatment. If this short-term treatment is stopped, fungi recur more often when fungistatic, rather than fungicidal, drugs have been used. Yeast infections such as those caused by Candida albicans respond less well to allylamine drugs. The azole drugs are often preferred for these types of infections. Nail infections are difficult to cure with topical therapies because the infections usually occur under the nail instead of on top of it and products penetrate poorly, if at all, through the nail plate. Infections of hair follicles, nails, and widespread infections often require systemic treatments. Antifungal agents are compounded into many different types of vehicles. Patients often prefer to treat weeping infections with spray formulations. Most physicians prescribe branded products in cream or lotion bases. Cost is a factor dictating prescription choice, especially since

  11. Fungal spores: hazardous to health?

    PubMed Central

    Sorenson, W G

    1999-01-01

    Fungi have long been known to affect human well being in various ways, including disease of essential crop plants, decay of stored foods with possible concomitant production of mycotoxins, superficial and systemic infection of human tissues, and disease associated with immune stimulation such as hypersensitivity pneumonitis and toxic pneumonitis. The spores of a large number of important fungi are less than 5 microm aerodynamic diameter, and therefore are able to enter the lungs. They also may contain significant amounts of mycotoxins. Diseases associated with inhalation of fungal spores include toxic pneumonitis, hypersensitivity pneumonitis, tremors, chronic fatigue syndrome, kidney failure, and cancer. PMID:10423389

  12. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  13. Invasive maxillary sinus aspergillosis: A case report successfully treated with voriconazole and surgical debridement

    PubMed Central

    Redondo-González, Luis-Miguel; Verrier-Hernández, Alberto

    2014-01-01

    Introduction: Invasive aspergillosis of the paranasal sinuses is a rare disease and often misdiagnosed; however, its incidence has seen substancial growth over the past 2 decades. Definitive diagnosis of these lesions is based on histological examination and fungal culture. Case Report: An 81-year-old woman with a history of pain in the left maxillary region is presented. The diagnosis was invasive maxillary aspergillosis in immunocompetent patient, which was successfully treated with voriconazole and surgical debridement. Possible clinical manifestations, diagnostic imaging techniques and treatment used are discussed. Since the introduction of voriconazole, there have been several reports of patients with invasive aspergillosis who responded to treatment with this new antifungal agent. Conclusions: We report the importance of early diagnosis and selection of an appropriate antifungal agent to achieve a successful treatment. Key words:Invasive aspergillosis, voriconazole, fungal sinusitis, antifungal agent, open sinus surgery. PMID:25593673

  14. Attacking invasive grasses

    USGS Publications Warehouse

    Keeley, Jon E.

    2015-01-01

    In grasslands fire may play a role in the plant invasion process, both by creating disturbances that potentially favour non-native invasions and as a possible tool for controlling alien invasions. Havill et al. (Applied Vegetation Science, 18, 2015, this issue) determine how native and non-native species respond to different fire regimes as a first step in understanding the potential control of invasive grasses.

  15. Invasive species in agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural production of food, feed, fiber or fuel is a local human activity with global ecological impacts, including the potential to foster invasions. Agriculture plays an unusual role in biological invasions, in that it is both a source of non-indigenous invasive species (NIS) and especially s...