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Sample records for acute invasive fungal

  1. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    PubMed Central

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-01-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients. PMID:26937339

  2. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia.

    PubMed

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-03-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients. PMID:26937339

  3. Invasive fungal diseases in patients with acute lymphoid leukemia.

    PubMed

    Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio

    2016-09-01

    Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis. PMID:26949001

  4. [Refractory acute myeloid leukemia developed malignancy-associated hemophagocytic lymphohistiocytosis during treatment of invasive fungal infection].

    PubMed

    Yamada, Ai; Moritake, Hiroshi; Sawa, Daisuke; Shimonodan, Hidemi; Kojima, Hitomi; Kamimura, Sachiyo; Nunoi, Hiroyuki

    2013-04-01

    We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients. PMID:23666221

  5. Pseudozyma aphidis fungaemia with invasive fungal pneumonia in a patient with acute myeloid leukaemia: case report and literature review.

    PubMed

    Joo, Hyonsoo; Choi, Yeon-Geun; Cho, Sung-Yeon; Choi, Jae-Ki; Lee, Dong-Gun; Kim, Hee-Je; Jo, Irene; Park, Yeon-Joon; Lee, Kyo-Young

    2016-01-01

    Pseudozyma species rarely cause invasive diseases in humans, which are usually isolated from plants. There have been anecdotal reports regarding Pseudozyma species infections in patients with underlying diseases or in neonates. However, clinical data and the pathogenicity in humans are still insufficient. We experienced a case of Pseudozyma aphidis fungaemia with invasive fungal pneumonia that developed during reinduction chemotherapy in a 51-year-old male with acute myeloid leukaemia (AML). P. aphidis was suspected based on the morphology of the yeast isolated from the blood and was confirmed via rDNA gene sequencing analysis. The patient successfully underwent stem cell transplantation with continuing antifungal treatment and finally completely recovered from both the AML and infectious complications. Here, we report a case of P. aphidis infection that developed during neutropenia in an AML patient and review the global literature. PMID:26608844

  6. 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. PMID:23711036

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

    ClinicalTrials.gov

    2016-08-23

    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

  8. 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

  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. Polymorphisms of Dectin-1 and TLR2 Predispose to Invasive Fungal Disease in Patients with Acute Myeloid Leukemia

    PubMed Central

    Fischer, Mike; Spies-Weisshart, Baerbel; Schrenk, Karin; Gruhn, Bernd; Wittig, Susan; Glaser, Anita; Hochhaus, Andreas

    2016-01-01

    Background Patients with acute myeloid leukemia (AML) who undergo induction chemotherapy are at high risk for invasive fungal disease (IFD). Dectin-1, a C-type lectin family member represents one of the most important pattern recognition receptors of the innate immune system and single nucleotide polymorphisms (SNPs) in the Dectin-1 gene have been associated with an increased risk of infectious complications. We sought to investigate the impact of three different Dectin-1 SNPs and one TLR2 SNP on developing IFD in 186 adult patients with newly diagnosed AML following anthracycline-based induction chemotherapy. Patients and methods Genotyping of Dectin-1 SNPs (rs16910526, rs3901533 and rs7309123) and TLR2 SNP (rs5743708) was performed by TaqMan method and pyrosequencing. IFD was defined according to the EORTC/MSG consensus guidelines. Multiple logistic regression analyses were applied to evaluate the association between the polymorphisms and the occurrence of pulmonary infections. Dectin-1 expression studies with SNP genotyped human monocytes were performed to elucidate susceptibility to IFD following chemotherapy. Results We could demonstrate that patients carrying the Dectin-1 SNP rs7309123 G/G (n = 47) or G/G and C/G (n = 133) genotype revealed a significant higher risk for developing both pneumonia in general (adjusted odds ratio (OR): 2.5; p = 0.014 and OR: 3.0, p = 0.004) and pulmonary IFD (OR: 2.6; p = 0.012 and OR: 2.4, p = 0.041, respectively). Patients carrying the TLR2 SNP rs5743708 (R753Q, GA/AA genotype, n = 12) also revealed a significantly higher susceptibility to pneumonia including IFD. Furthermore, Dectin-1 mRNA expression in human monocytes was lower following chemotherapy. Conclusion To our best knowledge, this study represents the first analysis demonstrating that harbouring polymorphisms of Dectin-1 (rs7309123) or TLR2 (rs5743708) represents an independent risk factor of developing IFD in patients with AML undergoing induction chemotherapy

  11. 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. PMID:25469955

  12. Invasive fungal infections in transplant recipients

    PubMed Central

    Miceli, Marisa H.; Alangaden, George

    2013-01-01

    Invasive fungal infections are an important cause of morbidity and mortality in hematopoietic stem cell transplant and solid organ transplant recipients. Evolving transplant modalities and techniques, complex and extensive immunosuppressant strategies, and the increased use of broad spectrum antifungal prophylaxis has greatly impacted the epidemiology and temporal pattern of invasive fungal infections in the transplant population. The goal of this article is to provide an up-to-date review of the most commonly encountered invasive fungal infections seen in transplant recipients, including epidemiology, risk factors, clinical features, diagnostic dilemmas, management and their overall influence on outcomes. PMID:25165546

  13. 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

  14. 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

  15. Incidence Density of Invasive Fungal Infections during Primary Antifungal Prophylaxis in Newly Diagnosed Acute Myeloid Leukemia Patients in a Tertiary Cancer Center, 2009 to 2011

    PubMed Central

    Mulanovich, Victor E.; Jiang, Y.; Lewis, Russell E.

    2014-01-01

    Although primary antifungal prophylaxis (PAP) is routinely administered in patients with acute myeloid leukemia (AML) during remission-induction and consolidation chemotherapy, the impact of PAP on the incidence of invasive fungal infections (IFIs) is not well described. We retrospectively analyzed the incidence of IFIs in 152 patients with AML who had been admitted to a tertiary cancer center between August 2009 and March 2011 and received PAP within 120 days after first remission-induction chemotherapy. We excluded patients who had undergone stem cell transplantation. Patients received a PAP drug with anti-Aspergillus activity during 72% (7,660/10,572) of prophylaxis-days. The incidence of documented IFIs (definite or probable according to revised European Organization for Research and Treatment of Cancer [EORTC] criteria) was 2.0/1,000 prophylaxis-days (95% confidence interval [CI], 1.23 to 3.04). IFIs due to molds were more common than IFIs due to yeasts (1.5/1,000 prophylaxis-days versus 0.4/1,000 prophylaxis-days; P = 0.01). Echinocandin-based PAP (8.6 and 7.1/1,000 prophylaxis-days, respectively) was associated with higher rates of documented IFIs than anti-Aspergillus azoles (voriconazole or posaconazole) (2.4 and 1.1/1,000 prophylaxis-days, respectively) at both 42 days (P = 0.03) and 120 days (P < 0.0001) after first remission-induction chemotherapy. The incidence of overall (documented and presumed) IFIs (P < 0.001), documented IFIs (P < 0.01), and empirical antifungal therapies (P < 0.0001) was higher during the first 42 days than after day 42. Despite the broad use of PAP with anti-Aspergillus activity, IFIs, especially molds, remain a significant cause of morbidity and mortality in AML patients, predominantly during the remission-induction phase. Patients receiving echinocandin-based PAP experienced higher rates of IFIs than did those receiving anti-Aspergillus azoles. PMID:24277033

  16. Opportunistic invasive fungal infections: diagnosis & clinical management

    PubMed Central

    Badiee, Parisa; Hashemizadeh, Zahra

    2014-01-01

    Invasive fungal infections are a significant health problem in immunocompromised patients. The clinical manifestations vary and can range from colonization in allergic bronchopulmonary disease to active infection in local aetiologic agents. Many factors influence the virulence and pathogenic capacity of the microorganisms, such as enzymes including extracellular phospholipases, lipases and proteinases, dimorphic growth in some Candida species, melanin production, mannitol secretion, superoxide dismutase, rapid growth and affinity to the blood stream, heat tolerance and toxin production. Infection is confirmed when histopathologic examination with special stains demonstrates fungal tissue involvement or when the aetiologic agent is isolated from sterile clinical specimens by culture. Both acquired and congenital immunodeficiency may be associated with increased susceptibility to systemic infections. Fungal infection is difficult to treat because antifungal therapy for Candida infections is still controversial and based on clinical grounds, and for molds, the clinician must assume that the species isolated from the culture medium is the pathogen. Timely initiation of antifungal treatment is a critical component affecting the outcome. Disseminated infection requires the use of systemic agents with or without surgical debridement, and in some cases immunotherapy is also advisable. Preclinical and clinical studies have shown an association between drug dose and treatment outcome. Drug dose monitoring is necessary to ensure that therapeutic levels are achieved for optimal clinical efficacy. The objectives of this review are to discuss opportunistic fungal infections, diagnostic methods and the management of these infections. PMID:24718393

  17. Fungal invasion of the rhizosphere microbiome.

    PubMed

    Chapelle, Emilie; Mendes, Rodrigo; Bakker, Peter A H M; Raaijmakers, Jos M

    2016-01-01

    The rhizosphere is the infection court where soil-borne pathogens establish a parasitic relationship with the plant. To infect root tissue, pathogens have to compete with members of the rhizosphere microbiome for available nutrients and microsites. In disease-suppressive soils, pathogens are strongly restricted in growth by the activities of specific rhizosphere microorganisms. Here, we sequenced metagenomic DNA and RNA of the rhizosphere microbiome of sugar beet seedlings grown in a soil suppressive to the fungal pathogen Rhizoctonia solani. rRNA-based analyses showed that Oxalobacteraceae, Burkholderiaceae, Sphingobacteriaceae and Sphingomonadaceae were significantly more abundant in the rhizosphere upon fungal invasion. Metatranscriptomics revealed that stress-related genes (ppGpp metabolism and oxidative stress) were upregulated in these bacterial families. We postulate that the invading pathogenic fungus induces, directly or via the plant, stress responses in the rhizobacterial community that lead to shifts in microbiome composition and to activation of antagonistic traits that restrict pathogen infection. PMID:26023875

  18. 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

  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. PMID:26153255

  20. Invasive Fungal Infections after Renal Transplantation

    PubMed Central

    Ezzatzadegan, S.; Chen, S.; Chapman, J. R.

    2012-01-01

    Background: Invasive fungal infection (IFI) is a leading cause of infection-related mortality among kidney allograft recipients.  Objective: To estimate the incidence and etiology of systemic fungal infection in renal allograft recipients in Sydney transplant facility. Methods: 471 kidney recipients, transplanted between 2000 and 2010 at the Westmead Hospital renal transplantation center, Sydney, Australia, were retrospectively surveyed. Results: IFI developed in 10 (2.1%) of 471 patients. With a mean±SD new kidney transplants per year of 42.9±13, the mean±SD incidence of IFI was 0.9±0.6 for each year of transplantation. 4 patients had received kidneys from living donors and 7 from cadavers with a mean±SD age of 50.5±14 years. The mean time to IFI was 33 months after transplantation with majority within the first 2 years. Cryptococcus neoformans was responsible for 50% of episodes (n=5) followed by Aspergillus fumigatus (n=3), and Pseudallescheria boydii (n=3); there was a single case of mucurmycosis. Lungs (n=5) followed by meninges (n=4) and skin (n=3) were the most commonly involved sites. Conclusion: IFI remains a major concern in renal transplantation. A high index of suspicion is required for early diagnosis and treatment to reduce the mortality. In this regard, appropriate diagnostic tests are necessary, particularly for C. neoformans. PMID:25013619

  1. 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. PMID:24565446

  2. 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

  3. 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. PMID:20163566

  4. 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. PMID:20678175

  5. Invasion of the Fungal Pathogen Batrachochytrium dendrobatidis on California Islands.

    PubMed

    Yap, Tiffany A; Gillespie, Lauren; Ellison, Silas; Flechas, Sandra V; Koo, Michelle S; Martinez, Ari E; Vredenburg, Vance T

    2016-03-01

    Batrachochytrium dendrobatidis (Bd), an amphibian fungal pathogen, has infected >500 species and caused extinctions or declines in >200 species worldwide. Despite over a decade of research, little is known about its invasion biology. To better understand this, we conducted a museum specimen survey (1910-1997) of Bd in amphibians on 11 California islands and found a pattern consistent with the emergence of Bd epizootics on the mainland, suggesting that geographic isolation did not prevent Bd invasion. We propose that suitable habitat, host diversity, and human visitation overcome isolation from the mainland and play a role in Bd invasion. PMID:26493624

  6. [Invasive fungal disease due to Scedosporium, Fusarium and mucorales].

    PubMed

    Pemán, Javier; Salavert, Miguel

    2014-01-01

    The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia. PMID:25442383

  7. 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

  8. 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

  9. 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. PMID

  10. Voriconazole in the management of nosocomial invasive fungal infections.

    PubMed

    Pemán, Javier; Salavert, Miguel; Cantón, Emilia; Jarque, Isidro; Romá, Eva; Zaragoza, Rafael; Viudes, Angel; Gobernado, Miguel

    2006-06-01

    Voriconazole is a new triazole developed for the treatment of life-threatening fungal infections. The drug is available for both oral and intravenous administration; the oral formulation has excellent bioavailability. The side-effect profile of voriconazole presents an acceptable safety and tolerability spectrum: transient visual disturbances, liver enzyme abnormalities, and skin rashes are the most frequently reported side effects but rarely lead to discontinuation. The potential for drug-drug interactions is high, because of its extensive hepatic metabolism. Careful attention to dosage is required, and serum levels and the effects of interacting drugs should be monitored. Review of 25 470 isolates of yeasts and 3216 isolates of filamentous fungi showed voriconazole to have broad-spectrum activity against pathogenic yeasts including intrinsically fluconazole-resistant isolates such as Candida krusei, dimorphic fungi, and opportunistic moulds like Aspergillus spp, amphotericin-B-resistant Aspergillus terreus, Fusarium spp, and Scedosporium apiospermum. It displays excellent clinical efficacy in patients with fluconazole-resistant and -susceptible Candida infections, invasive bone and central nervous system aspergillosis, and various refractory fungal infections. Voriconazole has been approved by the US Food and Drug Administration and by the European Medicines Agency for the treatment of invasive aspergillosis, serious infections caused by Fusarium and S. apiospermum, fluconazole-resistant invasive Candida infections, and candidemia in nonneutropenic patients. PMID:18360588

  11. 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

  12. Orbital Metastasis of Breast Cancer Mimicking Invasive Fungal Rhinosinusitis.

    PubMed

    Tabai, Mayara; Hazboun, Igor Moreira; Sakuma, Emerson Taro Inoue; Sampaio, Marcelo Hamilton; Sakano, Eulalia

    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

  13. Voriconazole in the management of nosocomial invasive fungal infections

    PubMed Central

    Pemán, Javier; Salavert, Miguel; Cantón, Emilia; Jarque, Isidro; Romá, Eva; Zaragoza, Rafael; Viudes, Ángel; Gobernado, Miguel

    2006-01-01

    Voriconazole is a new triazole developed for the treatment of life-threatening fungal infections. The drug is available for both oral and intravenous administration; the oral formulation has excellent bioavailability. The side-effect profile of voriconazole presents an acceptable safety and tolerability spectrum: transient visual disturbances, liver enzyme abnormalities, and skin rashes are the most frequently reported side effects but rarely lead to discontinuation. The potential for drug–drug interactions is high, because of its extensive hepatic metabolism. Careful attention to dosage is required, and serum levels and the effects of interacting drugs should be monitored. Review of 25 470 isolates of yeasts and 3216 isolates of filamentous fungi showed voriconazole to have broad-spectrum activity against pathogenic yeasts including intrinsically fluconazole-resistant isolates such as Candida krusei, dimorphic fungi, and opportunistic moulds like Aspergillus spp, amphotericin-B-resistant Aspergillus terreus, Fusarium spp, and Scedosporium apiospermum. It displays excellent clinical efficacy in patients with fluconazole-resistant and -susceptible Candida infections, invasive bone and central nervous system aspergillosis, and various refractory fungal infections. Voriconazole has been approved by the US Food and Drug Administration and by the European Medicines Agency for the treatment of invasive aspergillosis, serious infections caused by Fusarium and S. apiospermum, fluconazole-resistant invasive Candida infections, and candidemia in nonneutropenic patients. PMID:18360588

  14. Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies

    PubMed Central

    Riwes, Mary Mansour; Wingard, John R

    2013-01-01

    Invasive fungal disease is associated with increased morbidity and mortality in hematologic malignancy patients and hematopoietic stem cell transplant recipients. Timely recognition and treatment of invasive fungal diseases in these patients are essential and decrease mortality. However, conventional definitive diagnostic methods are difficult and time consuming. While conventional microbiological and histopathological methods are still needed for a definitive diagnosis of invasive fungal disease, new noninvasive diagnostic methods including serologic and molecular biomarkers are now available. These new diagnostic methods facilitate an early diagnosis of invasive fungal disease and allow for utilization of a pre-emptive treatment approach, which may ultimately lead to improved treatment outcomes and reduced toxicity. PMID:23216596

  15. 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

  16. 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. PMID:25352630

  17. 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

  18. 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

  19. Race and invasive fungal infection in solid organ transplant recipients.

    PubMed

    Boehme, Amelia K; McGwin, Gerald; Andes, David R; Lyon, G Marshall; Chiller, Tom; Pappas, Peter G; Baddley, John W

    2014-01-01

    Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases (n = 1,214) and controls (n = 16,550) were compared on demographic variables using chi-square, and the relationship between race and IFI was assesses with unconditional logistic regression. Compared to White transplant patients, Blacks had similar odds of developing IFI (OR = .97, 95% Cl 0.82-1.15, P = .7125), while participants who identified as other ethnicity were less likely to develop IFI (OR = .56, 95% Cl .41-.75, P < .001). Blacks, when compared to White patients, were at increased odds of developing cryptococcal infection (OR 2.19, 95% CI 1.35-3.54, P = .002). Despite pharmacogenetic differences, Black transplant recipients were not more likely overall to develop IFI compared to White transplant recipients. PMID:25065083

  20. [Invasive fungal infections in children: similarities and differences with adults].

    PubMed

    Ramos, J T; Francisco, L; Daoud, Z

    2016-09-01

    Invasive fungal infections (IFI) are a major cause of morbidity and mortality in immunocompromised adults and children. The purpose of this review was to update the epidemiological, clinical and therapeutic options in children, and to compare them with the adult population. Although there are important differences, the epidemiology, clinical features and risk factors for IFI have many similarities. Patient at risk include neutropenic hematology children, in whom Candida spp. y Aspergillus spp. predominate; primary immunodeficiencies, particularly chronic granulomatous disease with high susceptibility for Aspergillus spp.; and extremely premature infants, in whom C. albicans y C. parapsilosis are more prevalent. Premature babies are prone to dissemination, including the central nervous system. There are peculiarities in radiology and diagnostic biomarkers in children. In pulmonary aspergillosis, clasical signs in CT are usually absent. There is scant information on PCR and beta-D-glucan in children, and more limited on the performance of galactomannan enzyme immunoassay, that does not appear to be much different in neutropenic patients. There is a delay in the development of antifungals, limiting their use in children. Most azoles require therapeutic drug monitoring in children to optimize its safety and effectiveness. Pediatric treatment recommendations are mainly extrapolated from results of clinical trials performed in adults. There is no evidence for the benefit of preemptive therapy in children. It is necessary to foster specific pediatric studies with current and new antifungals to evaluate their pharmacokinetics, safety, and effectiveness at different ages in the pediatric population. PMID:27608317

  1. Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

    PubMed Central

    Lehrnbecher, Thomas; Schmidt, Stanislaw; Tramsen, Lars; Klingebiel, Thomas

    2013-01-01

    Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in promising strategies to enhance or restore critical immune functions in allogeneic HSCT recipients. Potential approaches include the administration of granulocytes, since neutropenia is the single most important risk factor for invasive fungal infection, and preliminary clinical results suggest a benefit of adoptively transferred donor-derived antifungal T cells. In vitro data and animal studies demonstrate an antifungal effect of natural killer cells, but clinical data are lacking to date. This review summarizes and critically discusses the available data of immunotherapeutic strategies in allogeneic HSCT recipients suffering from invasive fungal infection. PMID:23404543

  2. Risk factors for invasive fungal disease in critically ill adult patients: a systematic review

    PubMed Central

    2011-01-01

    Introduction Over 5,000 cases of invasive Candida species infections occur in the United Kingdom each year, and around 40% of these cases occur in critical care units. Invasive fungal disease (IFD) in critically ill patients is associated with increased morbidity and mortality at a cost to both the individual and the National Health Service. In this paper, we report the results of a systematic review performed to identify and summarise the important risk factors derived from published multivariable analyses, risk prediction models and clinical decision rules for IFD in critically ill adult patients to inform the primary data collection for the Fungal Infection Risk Evaluation Study. Methods An internet search was performed to identify articles which investigated risk factors, risk prediction models or clinical decisions rules for IFD in critically ill adult patients. Eligible articles were identified in a staged process and were assessed by two investigators independently. The methodological quality of the reporting of the eligible articles was assessed using a set of questions addressing both general and statistical methodologies. Results Thirteen articles met the inclusion criteria, of which eight articles examined risk factors, four developed a risk prediction model or clinical decision rule and one evaluated a clinical decision rule. Studies varied in terms of objectives, risk factors, definitions and outcomes. The following risk factors were found in multiple studies to be significantly associated with IFD: surgery, total parenteral nutrition, fungal colonisation, renal replacement therapy, infection and/or sepsis, mechanical ventilation, diabetes, and Acute Physiology and Chronic Health Evaluation II (APACHE II) or APACHE III score. Several other risk factors were also found to be statistically significant in single studies only. Risk factor selection process and modelling strategy also varied across studies, and sample sizes were inadequate for obtaining

  3. 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

  4. Successful treatment of an invasive fungal infection caused by Talaromyces sp. with voriconazole

    PubMed Central

    Sili, Uluhan; Bilgin, Huseyin; Masania, Rikesh; Eryuksel, Emel; Cimsit, Nuri Cagatay; Ayranci, Gulcicek; Richardson, Malcolm; Korten, Volkan

    2015-01-01

    Invasive fungal infections (IFI) are on the rise due to increasing numbers of immunosuppressed and critically ill patients. A malignant-looking pulmonary nodule in an immunosuppressed patient may indeed be caused by a fungal organism. We report a patient, who was eventually diagnosed with an IFI caused by an agent of hyalohyphomycosis, Talaromyces sp. determined via molecular methods and succesfully treated with voriconazole. PMID:25830087

  5. β-d-Glucan Testing Is Important for Diagnosis of Invasive Fungal Infections

    PubMed Central

    Doern, Christopher D.

    2013-01-01

    Invasive fungal infections are a significant cause of morbidity and mortality in patients who receive immunosuppressive therapy, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients. Many of the fungi associated with these infections are angioinvasive and are best diagnosed by visualizing the organism in or culturing the organism from deep tissue. However, obtaining such tissue often requires an invasive procedure. Many HSCT recipients are thrombocytopenic, making such procedure too risky because of potential bleeding complications. Additionally, positive blood cultures are rare for patients with angioinvasive fungal infections, making this diagnostic strategy of little value. Undiagnosed fungal infections in these patient populations are a significant cause of mortality. Prophylactic use of antifungal agents, such as the echinocandins, during periods of neutropenia or graft-versus-host disease may prevent some fungal infections but increase the risk for others. Detection of fungal antigens in body fluids, including cryptococcus capsular polysaccharide, histoplasma antigen, galactomannan, and β-d-glucan, is viewed as being clinically useful for at least the presumptive diagnosis of invasive fungal infections. β-d-Glucan is an attractive antigen in that it is found in a broad range of fungal agents, including the commonly encountered agents Candida spp., Aspergillus spp., and Pneumocystis jirovecii. Cross-reactions with certain hemodialysis filters, beta-lactam antimicrobials, and immunoglobulins, which raise concerns about false-positive tests, have also been described. As a result, the use of this testing must be closely monitored. In this point-counterpoint, we have asked Elitza Theel, who directs the Infectious Disease Serology Laboratory at the Mayo Clinic, to address why she believes that this test has value in the diagnosis of invasive fungal infections. We have asked Christopher Doern, Director of Clinical Microbiology at Children

  6. Invasive Fungal Sinusitis and Meningitis Due to Arthrographis kalrae in a Patient with AIDS

    PubMed Central

    Chin-Hong, Peter V.; Sutton, Deanna A.; Roemer, Marguerite; Jacobson, Mark A.; Aberg, Judith A.

    2001-01-01

    We report the first described case of Arthrographis kalrae pansinusitis and meningitis in a patient with AIDS. The patient was initially diagnosed with Arthrographis kalrae pansinusitis by endoscopic biopsy and culture. The patient was treated with itraconazole for approximately 5 months and then died secondary to Pneumocytis carinii pneumonia. Postmortem examination revealed invasive fungal sinusitis that involved the sphenoid sinus and that extended through the cribiform plate into the inferior surfaces of the bilateral frontal lobes. There was also an associated fungal meningitis and vasculitis with fungal thrombosis and multiple recent infarcts that involved the frontal lobes, right caudate nucleus, and putamen. Post mortem cultures were positive for A. kalrae. PMID:11158158

  7. 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

  8. 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

  9. Amphotericin B lipid complex in the management of invasive fungal infections in immunocompromised patients.

    PubMed

    Bassetti, Matteo; Aversa, Franco; Ballerini, Filippo; Benedetti, Fabio; Busca, Alessandro; Cascavilla, Nicola; Concia, Ercole; Tendas, Andrea; Di Raimondo, Francesco; Mazza, Patrizio; Nosari, Anna Maria; Rossi, Giuseppe

    2011-11-01

    Invasive fungal infections are associated with a poor outcome and their incidence is rising. Amphotericin B has for a long time been the gold standard for treatment of these infections, but the conventional formulation is associated with a high incidence of adverse events. Lipid formulations of amphotericin, developed to overcome these drawbacks, are now routinely used in clinical practice for the treatment of invasive fungal infections in immunocompromised patients. Amphotericin B lipid complex (ABLC) is prepared from amphotericin complexed to two phospholipids, a process that confers a number of important pharmacodynamic and pharmacokinetic properties compared with conventional amphotericin B. The results of retrospective observational studies and the analysis of databases, including the large Collaborative Exchange of Antifungal Research (CLEAR) database, have shown ABLC to be associated with response rates of up to about 80% in patients with confirmed fungal infections and around 60% in those treated empirically. Intranasal administration of ABLC for prophylaxis of invasive fungal infection in immunocompromised patients is safe and appears to be a promising treatment strategy for the future. ABLC is associated with a substantially lower incidence of nephrotoxicity than conventional amphotericin. Infusion-related reactions also occur less frequently than with conventional amphotericin and can be managed using premedication protocols. When direct and indirect costs are measured, ABLC appears to be less expensive than conventional amphotericin. The number of approved antifungal agents that are effective treatments for invasive fungal infections is increasing. However, lipid formulations of amphotericin, such as ABLC, are effective and well tolerated and remain the standard of care in the treatment of invasive fungal infections. Treatment strategies such as intranasal administration for prophylaxis and combination therapy with newer agents are future directions for

  10. Chronic and Invasive Fungal Infections in a Family with CARD9 Deficiency.

    PubMed

    Alves de Medeiros, Ana Karina; Lodewick, Evelyn; Bogaert, Delfien J A; Haerynck, Filomeen; Van Daele, Sabine; Lambrecht, Bart; Bosma, Sara; Vanderdonckt, Laure; Lortholary, Olivier; Migaud, Mélanie; Casanova, Jean-Laurent; Puel, Anne; Lanternier, Fanny; Lambert, Jo; Brochez, Lieve; Dullaers, Melissa

    2016-04-01

    Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp., dermatophytes (e.g., Trichophyton spp.) and phaeohyphomycetes (Exophiala spp., Phialophora verrucosa). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient. Two patients consented to genetic testing and were found to have a previously reported homozygous R70W CARD9 mutation. Circulating IL-17 and IL-22 producing T cells were decreased as was IL-6 and granulocyte/macrophage colony-stimulating factor (GM-CSF) secretion upon stimulation with Candida albicans. Patients with recurrent fungal infections in the absence of known immunodeficiencies should be analyzed for CARD9 gene mutations as the cause of fungal infection predisposition. PMID:26961233

  11. Invasive Fungal Sinusitis Caused by Scytalidium dimidiatum in a Lung Transplant Recipient

    PubMed Central

    Dunn, James J.; Wolfe, Michael J.; Trachtenberg, Joel; Kriesel, John D.; Orlandi, Richard R.; Carroll, Karen C.

    2003-01-01

    We describe a case of invasive fungal sinusitis caused by Scytalidium dimidiatum in a lung transplant recipient. Treatment was complicated by renal failure with amphotericin B therapies. Following 6 months of voriconazole treatment, the patient remained radiographically and clinically stable for a short time before dying of respiratory failure precipitated by graft rejection. PMID:14662991

  12. 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

  13. Approaches to management of invasive fungal infections in patients with hematologic malignancies.

    PubMed

    Forrest, Graeme N; Walsh, Thomas J

    2004-10-01

    Invasive fungal infections have become increasingly common in patients with hematologic malignancies, especially in those at high risk with prolonged neutropenia and graft versus host disease after allogeneic stem cell transplantation, and are associated with significant morbidity, mortality, and cost. New diagnostic techniques and therapeutic agents have emerged recently to assist in the management of these infections. The galactomannan assay in association with routine clinical and radiologic screening may assist in the early diagnosis of invasive aspergillosis such that therapy may be initiated early. Also, several new antifungal agents have become available, allowing the practitioner more options in the prevention and treatment of fungal infections. New antifungal agents such as the lipid amphotericin B products, voriconazole, and the echinocandins appear to be safer to use than conventional amphotericin B. Voriconazole also has shown superiority to conventional amphotericin B in the treatment of invasive aspergillosis, and its well absorbed oral formulation makes it an excellent treatment to complete therapy as an outpatient. All these therapeutic options allow physicians to tailor antifungal therapy to the individual patient based on response and toxicity to prevent or treat invasive fungal infections. There are several new antifungal agents in development, and future studies will evaluate combination therapies to determine safety and efficacy. PMID:18628154

  14. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient.

    PubMed

    Çetinkaya, Erdoğan; Çörtük, Mustafa; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  15. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient

    PubMed Central

    Çetinkaya, Erdoğan; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H. Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  16. Fungal rhinosinusitis and imaging modalities

    PubMed Central

    Gorovoy, Ian R.; Kazanjian, Mia; Kersten, Robert C.; Kim, H. Jane; Vagefi, M. Reza

    2012-01-01

    This report provides an overview of fungal rhinosinusitis with a particular focus on acute fulminant invasive fungal sinusitis (AFIFS). Imaging modalities and findings that aid in diagnosis and surgical planning are reviewed with a pathophysiologic focus. In addition, the differential diagnosis based on imaging suggestive of AFIFS is considered. PMID:23961027

  17. Managing invasive fungal infections: relying on clinical instincts or on a rational navigation system?

    PubMed

    de Pauw, Ben E; Viscoli, Claudio

    2011-01-01

    The management of invasive fungal disease in the immunocompromised host is complex and requires the specialized knowledge of physicians whose primary interest is actually the underlying disease rather than infectious complications. This Supplement aims to provide these physicians with some tools that may help to guide them through the maze of suspicion that an invasive fungal disease is present by offering an integrated care pathway of rational patient management. Such pathways will inevitably vary in detail in different centres and depend for their success on the presence of multidisciplinary teams and an explicit agreement on at least the minimum requirements for effective management. The integrated care pathways presented constitute an objective instrument to allow regular audits for recognizing opportunities to change practice if and when weaknesses are identified. PMID:21177405

  18. [Effects of Phyllostachys edulis invasion of native broadleaf forest on soil fungal community].

    PubMed

    Li, Yong-chun; Liang, Xue; Li, Yong-fu; Wang, Qi; Chen, Jun-hui; Xu, Qiu-fang

    2016-02-01

    To investigate variation of soil fungal community in response to invasion of Phyllostachys edulis into native broadleaf forest, we characterized the community structure and the abundance of fungi in soil under bamboo (BB), mixture forest of bamboo and broadleaf (MF) and broadleaf forest (BL) using terminal restriction fragment length polymorphism (T-RFLP) and real-time quantitative PCR. The results showed that the most obvious difference in the soil fungal community structure was observed between the BB and BF stands, followed by that between the MF and BL. Shannon index and evenness index of soil fungi were higher in the MF than in the BB and BL. pH and NH4+-N content were the most important environmental gradients on the distribution of fungal community under BB, while NO3(-)-N content significantly affected the distribution of the fungal community under BL. The abundance of fungi in BL was significantly higher than that in BB and MF, and the fungi abundance showed a negative correlation with soil pH but a positive correlation with NO3(-)-N content. These results implied that heterotrophic nitrification driven by fungi could occur in soil of BL, and this process might be changed by the bamboo invasion. PMID:27396134

  19. 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.

  20. 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. PMID:27074753

  1. Successful long-term management of invasive cerebral fungal infection following liver transplantation.

    PubMed

    Patel, Madhukar S; Wright, Alissa J; Kohn, Rachel; Markmann, James F; Kotton, Camille N; Vagefi, Parsia A

    2015-03-01

    Central nervous system (CNS) infections after liver transplantation may be fungal in aetiology, with involvement from either common organisms such as Cryptococcus neoformans and Aspergillus spp. as well as less common organisms, such as the Mucorales and Scedosporium spp. Although the mortality of CNS fungal infections was nearly 100% in early series, more recent data has suggested that good outcomes can be achieved. This may be due to both improved diagnostic capabilities, such as the ability to obtain fungal susceptibilities and therapeutic drug levels, and improved therapeutic options, such as the newer triazoles- voriconazole and posaconazole. Due to improved outcomes, issues have now arisen around the long-term tolerability of these agents. The following two cases of invasive cerebral fungal infections following liver transplantation, one with Aspergillus flavus, and the other with Scedosporium boydii/apiospermum highlight the success that can be seen with the modern management of a previously fatal diagnosis. In particular, we highlight the issues around therapeutic monitoring and discontinuation of therapy. PMID:25590987

  2. Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan

    PubMed Central

    2011-01-01

    Background Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era. Method A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009. Results Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS. Conclusions Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS. PMID:21939544

  3. Minimally Invasive Surgical Treatment of Acute Epidural Hematoma: Case Series

    PubMed Central

    2016-01-01

    Background and Objective. Although minimally invasive surgical treatment of acute epidural hematoma attracts increasing attention, no generalized indications for the surgery have been adopted. This study aimed to evaluate the effects of minimally invasive surgery in acute epidural hematoma with various hematoma volumes. Methods. Minimally invasive puncture and aspiration surgery were performed in 59 cases of acute epidural hematoma with various hematoma volumes (13–145 mL); postoperative follow-up was 3 months. Clinical data, including surgical trauma, surgery time, complications, and outcome of hematoma drainage, recovery, and Barthel index scores, were assessed, as well as treatment outcome. Results. Surgical trauma was minimal and surgery time was short (10–20 minutes); no anesthesia accidents or surgical complications occurred. Two patients died. Drainage was completed within 7 days in the remaining 57 cases. Barthel index scores of ADL were ≤40 (n = 1), 41–60 (n = 1), and >60 (n = 55); scores of 100 were obtained in 48 cases, with no dysfunctions. Conclusion. Satisfactory results can be achieved with minimally invasive surgery in treating acute epidural hematoma with hematoma volumes ranging from 13 to 145 mL. For patients with hematoma volume >50 mL and even cerebral herniation, flexible application of minimally invasive surgery would help improve treatment efficacy. PMID:27144170

  4. (1-3)-β-D-Glucan vs Galactomannan Antigen in Diagnosing Invasive Fungal Infections (IFIs)

    PubMed Central

    Fontana, C; Gaziano, R; Favaro, M; Casalinuovo, IA; Pistoia, ES; Di Francesco, P

    2012-01-01

    Invasive fungal infections (IFIs) are serious and often life-threatening complications in patients with haematological malignancies. Early diagnosis and the initiation of efficacious antifungal treatments could affect the prognosis of these patients. The detection of (1-3)-β-D-Glucan (BDG) could be a promising non-culture-based, noninvasive tool for IFI analyses in haemato-oncological patients, allowing the diagnosis of the two major IFIs, invasive aspergillosis (IA) and invasive candidiasis (IC), with a single test. The aim of this work was to evaluate and compare the use of the BDG in combination with the galactomannan antigen (GAL) assay in order to exclude or confirm suspected IFIs. Sera from 46 haemato-oncological patients (24 with proven/probable IFI and 22 without IFI symptoms) were evaluated retrospectively for the detection of GAL and BDG. In 24 patients, the serum BDG levels facilitated IFI diagnosis: 18 probable IA, 3 proven IA and 3 IC. In the remaining 22 patients, the BDG level helped exclude IFIs. The BDG was positive earlier than GAL in 5/24 cases [three of probable invasive aspergillosis (IA), one of proven IA and one case of proven invasive candidiasis (IC)] and was positive at the same time as GAL in 19/24 cases; in no case was GAL positive before BDG was. The BDG detection is useful, however, the test has a great limitation because it is a completely manual procedure. PMID:22942923

  5. Epidemiology of invasive fungal diseases on the basis of autopsy reports.

    PubMed

    Dignani, María Cecilia

    2014-01-01

    Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality among immunocompromised patients and cost to health services. They are difficult to prevent, diagnose, and treat. This difficulty in diagnosis leads us to treat them empirically by using several tools, including epidemiological data, non-culture methods and images. Most of the available epidemiological information may not be accurate because we are dealing with a disease that only has an estimated 50% chance of being diagnosed before death. Therefore, autopsy reports become a valuable tool, not only to define the real epidemiology, but also to address the trend in pre-mortem diagnosis, which is the best marker available to prove the efficiency of the research in IFD. This article reviews and analyzes the data on IFD obtained from 11 single-center, multi-center and nationwide autopsy reports published between 2008 and 2013, and also discusses the issues we need to address in order to improve the quality of the epidemiological data on invasive fungal disease obtained from autopsy reports. PMID:25343038

  6. Epidemiology of invasive fungal diseases on the basis of autopsy reports

    PubMed Central

    2014-01-01

    Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality among immunocompromised patients and cost to health services. They are difficult to prevent, diagnose, and treat. This difficulty in diagnosis leads us to treat them empirically by using several tools, including epidemiological data, non-culture methods and images. Most of the available epidemiological information may not be accurate because we are dealing with a disease that only has an estimated 50% chance of being diagnosed before death. Therefore, autopsy reports become a valuable tool, not only to define the real epidemiology, but also to address the trend in pre-mortem diagnosis, which is the best marker available to prove the efficiency of the research in IFD. This article reviews and analyzes the data on IFD obtained from 11 single-center, multi-center and nationwide autopsy reports published between 2008 and 2013, and also discusses the issues we need to address in order to improve the quality of the epidemiological data on invasive fungal disease obtained from autopsy reports. PMID:25343038

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

    PubMed Central

    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. PMID:26392781

  8. Invasive candidiasis in critical care setting, updated recommendations from “Invasive Fungal Infections-Clinical Forum”, Iran

    PubMed Central

    Elhoufi, Ashraf; Ahmadi, Arezoo; Asnaashari, Amir Mohammad Hashem; Davarpanah, Mohammad Ali; Bidgoli, Behrooz Farzanegan; Moghaddam, Omid Moradi; Torabi-Nami, Mohammad; Abbasi, Saeed; El-Sobky, Malak; Ghaziani, Ali; Jarrahzadeh, Mohammad Hossein; Shahrami, Reza; Shirazian, Farzad; Soltani, Farhad; Yazdinejad, Homeira; Zand, Farid

    2014-01-01

    Invasive candidiasis (IC) bears a high risk of morbidity and mortality in the intensive care units (ICU). With the current advances in critical care and the use of wide-spectrum antibiotics, invasive fungal infections (IFIs) and IC in particular, have turned into a growing concern in the ICU. Further to blood cultures, some auxiliary laboratory tests and biomarkers are developed to enable an earlier detection of infection, however these test are neither consistently available nor validated in our setting. On the other hand, patients’ clinical status and local epidemiology data may justify the empiric antifungal approach using the proper antifungal option. The clinical approach to the management of IC in febrile, non-neutropenic critically ill patients has been defined in available international guidelines; nevertheless such recommendations need to be customized when applied to our local practice. Over the past three years, Iranian experts from intensive care and infectious diseases disciplines have tried to draw a consensus on the management of IFI with a particular focus on IC in the ICU. The established IFI-clinical forum (IFI-CF), comprising the scientific leaders in the field, has recently come up with and updated recommendation on the same (June 2014). The purpose of this review is to put together literature insights and Iranian experts’ opinion at the IFI-CF, to propose an updated practical overview on recommended approaches for the management of IC in the ICU. PMID:25374806

  9. 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

  10. 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. PMID:26730212

  11. 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

  12. Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis?

    PubMed

    Pomares, Helena; Arnan, Montserrat; Sánchez-Ortega, Isabel; Sureda, Anna; Duarte, Rafael F

    2016-08-01

    The aim of this study is to analyse the risk of invasive fungal infection (IFI) and the need for antifungal prophylaxis in patients with acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in 121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5, range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one probable aspergillosis and one proven candidemia) occurred in this series. The incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per patient treated in those with severe neutropenia. Two patients died from IFI, leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per treatment cycle. The numbers needed to treat with prophylaxis to prevent one case of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment course, and 137 azacitidine cycles or 24 patients among those with severe neutropenia. AML/MDS patients treated with azacitidine, including those with severe prolonged neutropenia, have a very low risk of IFI which does not justify the use of antifungal prophylaxis. PMID:27027972

  13. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.

    PubMed

    Drewniak, Agata; Gazendam, Roel P; Tool, Anton T J; van Houdt, Michel; Jansen, Machiel H; van Hamme, John L; van Leeuwen, Ester M M; Roos, Dirk; Scalais, Emmanuel; de Beaufort, Carine; Janssen, Hans; van den Berg, Timo K; Kuijpers, Taco W

    2013-03-28

    Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule in the cytosol of myeloid cells, required for induction of T-helper cells producing interleukin-17 (Th17 cells) and important in antifungal immunity. In a patient suffering from Candida dubliniensis meningoencephalitis, mutations in the CARD9 gene were found to result in the loss of protein expression. Apart from the reduced numbers of CD4(+) Th17 lymphocytes, we identified a lack of monocyte-derived cytokines in response to Candida strains. Importantly, CARD9-deficient neutrophils showed a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae. The neutrophil killing defect was independent of the generation of reactive oxygen species by the reduced NAD phosphate oxidase system. Taken together, this demonstrates that human CARD9 deficiency results in selective defect in the host defense against invasive fungal infection, caused by an impaired phagocyte killing. PMID:23335372

  14. 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. PMID:12679266

  15. Breakthrough invasive fungal diseases during echinocandin treatment in high-risk hospitalized hematologic patients.

    PubMed

    Chan, Thomas S Y; Gill, Harinder; Hwang, Yu-Yan; Sim, Joycelyn; Tse, Alan C T; Loong, Florence; Khong, Pek-Lan; Tse, Eric; Leung, Anskar Y H; Chim, Chor-Sang; Lie, Albert K W; Kwong, Yok-Lam

    2014-03-01

    The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N = 173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C. parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor. PMID:23949318

  16. [Microbiological procedures for the diagnosis, management, and study of invasive fungal infections].

    PubMed

    Canton, Emilia; García-Rodríguez, Julio; Martín-Mazuelos, Estrella; Pemán, Javier; Guinea, Jesús

    2014-01-01

    Invasive fungal infections (IFIs) are difficult to diagnose and cause a high mortality to an expanding spectrum of patients. Culture of clinical samples has limitations for the diagnosis of IFI and alternative procedures have been developed. Among them, serum determination of galactomannan or beta-1,3-d-glucan, and antimicelium and antimannan antibodies are relevant. The use of molecular procedures and mass spectrometry (MALDI-TOF) are encouraging tools for the optimization of the diagnosis and management of patients with IFI. The proposal of species-specific breakpoint to classify the isolates as resistant or susceptible to antifungal agents and the necessity of monitor the azole serum levels deserve greater attention. PMID:23499525

  17. Geographical and temporal changes of foliar fungal endophytes associated with the invasive plant Ageratina adenophora.

    PubMed

    Mei, Liang; Zhu, Ming; Zhang, De-Zhu; Wang, Yong-Zhou; Guo, Jing; Zhang, Han-Bo

    2014-02-01

    Endophytes may gradually accumulate in the new geographic range of a non-native plant, just as pathogens do. To test this hypothesis, the dynamics of colonization and diversity of foliar fungal endophytes of non-native Ageratina adenophora were investigated. Previous reports showed that the time since the initial introduction (1930s) of A. adenophora into China varied among populations. Endophytes were sampled in three provinces of Southwest China in 21 sites that varied from 20 to 70 years since the introduction of A. adenophora from its native Central America. Endophyte isolation frequencies varied from 1.87% to 60.23% overall in a total of 4,032 leaf fragments. Based on ITS sequence variations, 463 fungal endophytes were distinguished as 112 operational taxonomic units (OTUs) belonging to the Sordariomycetes (77 OTUs, 373 isolates), Dothideomycetes (18 OTUs, 38 isolates), and Agaricomycetes (17 OTUs, 52 strains) classes. Colletotrichum (28.51%), Nemania (14.90%), Phomopsis (13.17%), and Xylaria (4.97%) were the most abundant genera. Both endophyte diversity and overall isolation frequency increased with time since introduction. The genetic differentiation of the fungus Colletotrichum gloeosporioides indicated that the dispersal of endophytes was likely affected by a combination of geographic factors and the invasion history of the host A. adenophora. PMID:24276537

  18. An observational efficacy and safety analysis of the treatment of acute invasive aspergillosis using voriconazole.

    PubMed

    Jacobs, F; Selleslag, D; Aoun, M; Sonet, A; Gadisseur, A

    2012-06-01

    The purpose of this study was to evaluate efficacy and safety of voriconazole in patients with acute invasive aspergillosis (IA) in a real-life, clinical setting. This was a multicenter observational study in adult patients treated with voriconazole for invasive mycosis. The study evaluated clinical response, mortality, use of other licensed antifungal therapy (OLAT), and treatment duration. This sub-analysis evaluated treatment and outcome data specifically from adult patients with proven/probable IA, while safety data were assessed in patients with proven/probable/possible IA. Of the 141 patients enrolled, 113 were adults with proven/probable IA and six had possible IA. Voriconazole treatment duration ranged from 1 to 183 days (median, 49.5 days). Voriconazole was used exclusively in 64% (72/113) of patients and in combination/sequentially with OLAT in 36%. Overall successful treatment response was 50% (57/113 patients). Twelve percent (14/113) of patients were switched to OLAT, either because of insufficient response (four patients) or for safety reasons (10 patients). Overall and attributable (entirely or partially due to fungal infection) mortality rates were 52% (59/113) and 17%, respectively. Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials demonstrating voriconazole as an effective and safe agent for treatment of confirmed acute IA. PMID:21971820

  19. Bronchogenic Carcinoma with Cardiac Invasion Simulating Acute Myocardial Infarction

    PubMed Central

    Das, Anirban; Das, Sibes K.; Pandit, Sudipta; Karmakar, Rathindra Nath

    2016-01-01

    Cardiac metastases in bronchogenic carcinoma may occur due to retrograde lymphatic spread or by hematogenous dissemination of tumour cells, but direct invasion of heart by adjacent malignant lung mass is very uncommon. Pericardium is frequently involved in direct cardiac invasion by adjacent lung cancer. Pericardial effusion, pericarditis, and tamponade are common and life threatening presentation in such cases. But direct invasion of myocardium and endocardium is very uncommon. Left atrial endocardium is most commonly involved in such cases due to anatomical contiguity with pulmonary hilum through pulmonary veins, and in most cases left atrial involvement is asymptomatic. But myocardial compression and invasion by adjacent lung mass may result in myocardial ischemia and may present with retrosternal, oppressive chest pain which clinically may simulate with the acute myocardial infarction (AMI). As a result, it leads to misdiagnosis and delayed diagnosis of lung cancer. Here we report a case of non-small-cell carcinoma of right lung which was presented with asymptomatic invasion in left atrium and retrosternal chest pain simulating AMI due to myocardial compression by adjacent lung mass, in a seventy-four-year-old male smoker. PMID:27042370

  20. Population-Based Analysis of Invasive Fungal Infections, France, 2001–2010

    PubMed Central

    Bitar, Dounia; Lortholary, Olivier; Le Strat, Yann; Nicolau, Javier; Coignard, Bruno; Tattevin, Pierre; Dromer, Françoise

    2014-01-01

    To determine the epidemiology and trends of invasive fungal infections (IFIs) in France, we analyzed incidence, risk factors, and in-hospital death rates related to the most frequent IFIs registered in the national hospital discharge database during 2001–2010. The identified 35,876 IFI cases included candidemia (43.4%), Pneumocystis jirovecii pneumonia (26.1%), invasive aspergillosis (IA, 23.9%), cryptococcosis (5.2%), and mucormycosis (1.5%). The overall incidence was 5.9/100,000 cases/year and the mortality rate was 27.6%; both increased over the period (+1.5%, +2.9%/year, respectively). Incidences substantially increased for candidemia, IA, and mucormycosis. Pneumocystis jirovecii pneumonia incidence decreased among AIDS patients (−14.3%/year) but increased in non-HIV–infected patients (+13.3%/year). Candidemia and IA incidence was increased among patients with hematologic malignancies (>+4%/year) and those with chronic renal failure (>+10%/year). In-hospital deaths substantially increased in some groups, e.g., in those with hematologic malignancies. IFIs occur among a broad spectrum of non–HIV-infected patients and should be a major public health priority. PMID:24960557

  1. 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

  2. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China.

    PubMed

    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

    2015-02-01

    This stud y examined the epidemiology, risk factors, management, and outcome of invasive fungal infection (IFI) in patients receiving chemotherapy for hematological malignancy in China. IFI risk factors were analyzed using univariate analysis and multivariate logistic regression. In total, 4,192 patients receiving 4,889 chemotherapy courses were enrolled [mean age 40.7 years, 58.4% male, 16.9% children (<18 years)]. The most common hematological diseases were acute myeloid leukemia (AML, 28.5%), non-Hodgkin lymphoma (NHL, 26.3%), and acute lymphoblastic leukemia (ALL, 20.2%). Severe neutropenia (absolute neutrophil count [ANC] <500/mm(3)) occurred after one third (1,633/4,889, 33.4%) of chemotherapy courses. Incidence of proven/probable IFI was 2.1% per chemotherapy course and higher in patients with myelodysplastic syndrome (MDS, 4.94%), acute hyperleukocytic leukemia (AHL, 4.76%), AML (3.83%), or induction chemotherapy. Risk factors included ANC <500/mm(3) [odds ratio (OR) 3.60], AML or MDS (OR 1.97), induction chemotherapy (OR 2.58), previous IFI (OR 3.08), and being male (OR 1.74). Antifungal agents, prescribed in one quarter (1,211/4,889, 24.8%) of chemotherapy courses, included primary/secondary prophylaxis (n = 827, 16.9%) and/or treatment (n = 655, 13.4%; 86.9 % triazoles), which was empirical (84.3%), pre-emptive (8.6%), or targeted (7.1%). Overall mortality following each chemotherapy course (1.5%) increased in proven/probable (11.7%) and possible IFI (8.2%). In summary, IFI was more common in MDS, AHL, AML, or induction chemotherapy, and substantially increased mortality. Neutropenic patients receiving induction chemotherapy for AML or MDS and those with previous IFI were at particular risk. Antifungal prophylaxis showed an independent protective effect but was not commonly used, even in high-risk patients. By contrast, empiric antifungals were widely used. PMID:25293517

  3. Invasive fungal infections in neutropenic enterocolitis: A systematic analysis of pathogens, incidence, treatment and mortality in adult patients

    PubMed Central

    Gorschlüter, Marcus; Mey, Ulrich; Strehl, John; Schmitz, Volker; Rabe, Christian; Pauls, Katharina; Ziske, Carsten; Schmidt-Wolf, Ingo GH; Glasmacher, Axel

    2006-01-01

    Background Neutropenic enterocolitis is a life-threatening complication most frequently occurring after intensive chemotherapy in acute leukaemias. Gramnegative bacteria constitute the most important group of causative pathogens. Fungi have also been reported, but their practical relevance remains unclear. The guidelines do not address concrete treatment recommendations for fungal neutropenic enterocolitis. Methods Here, we conducted a metaanalysis to answer the questions: What are frequency and mortality of fungal neutropenic enterocolitis? Do frequencies and microbiological distribution of causative fungi support empirical antimycotic therapy? Do reported results of antimycotic therapy in documented fungal neutropenic enterocolitis help with the selection of appropriate drugs? Following a systematic search, we extracted and summarised all detail data from the complete literature. Results Among 186 articles describing patients with neutropenic enterocolitis, we found 29 reports describing 53 patients with causative fungal pathogens. We found no randomised controlled trial, no good quality cohort study and no good quality case control study on the role of antifungal treatment. The pooled frequency of fungal neutropenic enterocolitis was 6.2% calculated from all 860 reported patients and 3.4% calculated from selected representative studies only. In 94% of the patients, Candida spp. were involved. The pooled mortality rate was 81.8%. Most authors did not report or perform antifungal therapy. Conclusion In patients with neutropenic enterocolitis, fungal pathogens play a relevant, but secondary role compared to bacteria. Evidence concerning therapy is very poor, but epidemiological data from this study may provide helpful clues to select empiric antifungal therapy in neutropenic enterocolitis. PMID:16504141

  4. Acute Lumbar Burst Fracture Treated by Minimally Invasive Lateral Corpectomy

    PubMed Central

    Amaral, Rodrigo; Marchi, Luis; Oliveira, Leonardo; Coutinho, Thiago

    2013-01-01

    Burst fractures in acute spinal traumas are a difficult problem to solve. Different approaches and techniques have been utilized, but with high incidence of morbidity and mortality, besides unsatisfactory clinical and radiological results. Mini-open approaches recently emerged and have been shown to be safe and effective in the treatment of several spinal conditions. Here we report a case of acute lumbar burst fracture at L2 treated by minimally invasive true lateral approach posteriorly instrumented with percutaneous pedicle screws. The minimum disruptive access in addition to a rigid construction allowed a lumbar corpectomy without the morbidity of standard open approaches, lowering surgery costs and accelerating the patient recovery with successfully clinical and radiological results. PMID:23634314

  5. [Invasive diagnosis, transcatheter and surgical treatment of acute coronary syndromes].

    PubMed

    Fabián, J; Hricák, V; Fridrich, V; Fischer, V

    1998-01-01

    On the basis of long-term personal experiences and critical evaluation of the present literatury sources authors described the role of invasive diagnostic methods and transcathetral and cardiosurgical possibilities in the recognition and therapy of acute coronary syndromes. These techniques are, and in the forthcoming year shall be available only in specialized institutions. The paper describes the indication for these aggressive techniques as well as their limitations and complications. The goal of the presented article is to inform both the cardiological and frequently broad physicians' societies about the possibilities of diaventional cardiology and cardiosurgery which will be gradually more applied in the care of the patients with acute coronary syndromes. (Ref. 39, Tab. 2, Fig. 3.) PMID:9919748

  6. Extrasinonasal infiltrative process associated with a sinonasal fungus ball: does it mean invasive fungal sinusitis?

    PubMed Central

    Kim, Yi-Kyung; Kim, Hyung-Jin; Kim, Hyo Yeol; Cha, Jihoon; Lee, Ji Young; Chung, Seung-Kyu; Dhong, Hun-Jong; Song, Mina; Kim, Sung Tae

    2016-01-01

    PURPOSE Invasive fungal sinusitis (IFS) has rarely been reported to develop from non-IFS. The purpose of this study was to disclose the nature of the extrasinonasal infiltrative process in the presence of a sinonasal fungus ball (FB). METHODS We retrospectively reviewed the medical records, computed tomography, magnetic resonance images of 13 patients with sinonasal FB and the extrasinonasal infiltrative process. Based on histology and clinical course, we divided the extrasinonasal infiltrative process into IFS and the nonfungal inflammatory/infectious process (NFIP). The images were analyzed with particular attention to the presence of cervicofacial tissue infarction (CFTI). RESULTS Of the 13 patients, IFS was confirmed in only one, while the remaining 12 were diagnosed to have presumed NFIP. One patient with IFS died shortly after diagnosis. In contrast, all 12 patients with presumed NFIP, except one, survived during a mean follow-up of 17 months. FB was located in the maxillary sinus (n=4), sphenoid sinus (n=8), and both sinuses (n=1). Bone defect was found in five patients, of whom four had a defect in the sphenoid sinus. Various sites were involved in the extrasinonasal infiltrative process, including the orbit (n=10), intracranial cavity (n=9), and soft tissues of the face and neck (n=7). CFTI was recognized only in one patient with IFS. CONCLUSION In most cases, the extrasinonasal infiltrative process in the presence of sinonasal FB did not seem to be caused by IFS but probably by NFIP. In our study, there were more cases of invasive changes with the sphenoid than with the maxillary FB. PMID:27283592

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

    PubMed

    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

  8. Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients.

    PubMed

    Hol, J A; Wolfs, T F W; Bierings, M B; Lindemans, C A; Versluys, A B J; Wildt de, A; Gerhardt, C E; Boelens, J J

    2014-01-01

    This study was aimed at finding predictors of invasive fungal infection (IFI) after pediatric allogeneic hematopoietic SCT (HSCT). All children who received allogeneic HSCT in the Wilhelmina Children's Hospital Utrecht between 2004 and 2012 were included. HSCT data were prospectively collected. Patients were retrospectively classified into high- or low-risk groups for developing IFI using criteria based on available literature. Predictors for the occurrence of IFI were analyzed using Cox regression models. We used logistic regression models to analyze the association between other HSCT-related complications and IFI. Secondary outcomes were overall survival and treatment-related mortality (TRM). Two-hundred nine patients were included in the analysis; median age was 6.6 years. The cumulative incidence of IFI was 12%. In patients classified as 'low risk' (n=75), only 5.3% developed IFI (odds ratio (OR): 0.325; P=0.047). In multivariate analysis, a predictor for the occurrence of IFI was an a priori determined HSCT TRM risk >20% (based on EBMT-risk score). Post-HSCT, the administration of high-dose steroids was associated with IFI (OR: 4.458; P=0.010). Patients who developed IFI showed an increased risk of TRM (OR: 3.773; P=0.004). These results confirm that risk group stratification should guide intensity of monitoring for IFI and use of antifungal prophylaxis. PMID:24121212

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

    PubMed Central

    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. PMID:26949702

  10. Invasive fungal infection in neonatal intensive care units: a multicenter survey.

    PubMed

    Baptista, Monica Isabel; Nona, José; Ferreira, Marta; Sampaio, Isabel; Abrantes, Margarida; Tomé, Maria Teresa; Neto, Maria Teresa; Barroso, Rosalina; Serelha, Micaella; Virella, Daniel

    2016-02-01

    This study assesses the epidemiology of invasive fungal infection (IFI) in Portuguese Neonatal Intensive Care Units (NICUs) and compares the effectiveness and safety of antifungal therapies. A survey concerning the period 2005-2010 was carried out in NICUs of Greater Lisbon. Among 10 473 admitted neonates, 44 cases were identified, 29 among extreme low birth weight neonates (65.9%). Cumulative incidence rate was 0.42% (95%CI 0.309-0.559). A central vascular catheter was present before IFI in all cases. Candida albicans and Candida parapsilosis were the most frequent isolates. The initial antifungic was fluconazole in 22 cases and liposomal amphotericin B (L-AmB) in 18. Therapy was switched in 10 patients on fluconazole and 3 on L-AmB. Case fatality rate was 11.4% (95%CI 4.39-23.91). No serious adverse drugs reactions (SADRs) or clinical side effects were observed. The knowledge of the local epidemiology helps to identify adequate prophylactic and treatment strategies. PMID:25365503

  11. Current strategies against invasive fungal infections in patients with aplastic anemia, strong power and weak weapon, a case report and review of literature.

    PubMed

    Zekavat, Omid Reza; Amanati, Ali; Saleh, Fazl; Abdolkarimi, Babak; Fathpour, Gholamreza; Badiee, Parisa; Geramizadeh, Bita

    2016-03-01

    We report an 18 year old boy with Aplastic anemia complicated by serious fungal rhinosinusitis. Despite prompt treatment and early repeated surgical debridements, he died after about more than 6 weeks of hard challenges with fungal infections. Current strategies against invasive fungal infections (IFIs) in patients with Aplastic anemia may be inadequate for the management of serious complications. Antifungal prophylaxis is highly recommended in pre-transplant period for severe form of Aplastic anemia. PMID:27047751

  12. Voriconazole is a safe and effective anti-fungal prophylactic agent during induction therapy of acute myeloid leukemia

    PubMed Central

    Shah, Akash; Ganesan, Prasanth; Radhakrishnan, Venkatraman; Kannan, Krishnarathinam; Rajendranath, Rejiv; Mahajan, Vandana; Vijayakumar, Varalakshmi; Ganesan, Trivadi; Sagar, Tenali Gnana

    2016-01-01

    Background: Antifungal prophylaxis (AFP) reduces the incidence of invasive fungal infections (IFIs) during induction therapy of acute myeloid leukemia (AML). Posaconazole is considered the standard of care. Voriconazole, a generic cheaper alternative is a newer generation azole with broad anti-fungal activity. There is limited data on the use of voriconazole as a prophylactic drug. Materials and Methods: A single-center, prospective study was performed during which patients with AML undergoing induction chemotherapy received voriconazole as AFP (April 2012 to February 2014). Outcomes were compared with historical patients who received fluconazole as AFP (January 2011-March 2012, n = 66). Results: Seventy-five patients with AML (median age: 17 years [range: 1-75]; male:female 1.6:1) received voriconazole as AFP. The incidence of proven/probable/possible (ppp) IFI was 6.6% (5/75). Voriconazole and fluconazole cohorts were well-matched with respect to baseline characteristics. Voriconazole (when compared to fluconazole) reduced the incidence of pppIFI (5/75, 6.6% vs. 19/66, 29%; P < 0.001), need to start therapeutic (empiric + pppIFI) antifungals (26/75, 34% vs. 51/66, 48%; P < 0.001) and delayed the start of therapeutic antifungals in those who needed it (day 16 vs. day 10; P < 0.001). Mortality due to IFI was also reduced with the use of voriconazole (1/75, 1.3% vs. 6/66, 9%; P = 0.0507), but this was not significant. Three patients discontinued voriconazole due to side-effects. Conclusion: Voriconazole is an effective and safe oral agent for IFI prophylaxis during induction therapy of AML. Availability of generic equivalents makes this a more economical alternative to posaconazole. PMID:27051159

  13. Basilar Artery Territory Stroke Secondary to Invasive Fungal Sphenoid Sinusitis: A Case Report and Review of the Literature

    PubMed Central

    Fu, Katherine A.; Nguyen, Peggy L.; Sanossian, Nerses

    2015-01-01

    Background Mucormycosis is a fungal infection with the following 5 classic forms: cutaneous, pulmonary, gastrointestinal, disseminated, and rhinocerebral. The rhinocerebral form can be rapidly progressive and invasive with a high mortality rate. We present a case of a 38-year-old man with invasive mucormycosis that led to a basilar artery territory stroke. Rhinocerebral mucormycosis is an unusual cause of stroke. Case Report A 38-year-old man with a past medical history of diabetes mellitus presented with altered mental status. A lumbar puncture revealed eosinophilic pleocytosis with a mildly elevated total protein and borderline low glucose level. CT revealed a left medullary and cerebellar infarct confirmed by MRI. MRI also displayed a diffuse marrow signal abnormality in the clivus with contiguous sinus disease. Endoscopic sinus surgery confirmed that the fungal sinusitis was mucormycosis of the Rhizopus genus, which had affected the left sphenoid sinus, invaded through the skull base, and involved the basilar artery. He was given liposomal amphotericin (500 mg i.v.) with posaconazole (400 mg i.v. twice daily). Due to the severity of the invasion and poor prognosis, the patient was discharged with comfort care measures. Discussion Clinicians should be aware of invasive sinusitis as a rare cause of stroke in diabetics. Once the subarachnoid space and basal arteries of the brain have been invaded, the prognosis is very poor. The key to improvement of outcomes is early recognition and treatment, and examination of the sinuses on neuroimaging in all cases of stroke is vital. PMID:25873889

  14. Chronic invasive fungal rhinosinusitis by Paecilomyces variotii: A rare case report.

    PubMed

    Swami, T; Pannu, S; Kumar, Mukesh; Gupta, G

    2016-01-01

    Fungal infection of the paranasal sinuses is an increasingly recognised entity, both in normal and immunocompromised individuals. The recent increase in mycotic nasal and paranasal infections is due to both improved diagnostic research and an increase in the conditions that favour fungal infection. Aspergillus, Candida, and Mucor species are the most common causative agents of fungal sinusitis, but infection with lesser known species have been reported across the world infrequently. This article reviews and presents a case report of chronic fungal sinusitis in an immunocompetent adult male infected with Paecilomyces variotii which is opportunistic soil saprophyte, uncommon to humans. PMID:26776131

  15. 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

  16. Sinonasal Fungal Infections and Complications: A Pictorial Review.

    PubMed

    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

  17. Invasive fungal disease in university hospital: a PCR-based study of autopsy cases

    PubMed Central

    Ruangritchankul, Komkrit; Chindamporn, Ariya; Worasilchai, Navaporn; Poumsuk, Ubon; Keelawat, Somboon; Bychkov, Andrey

    2015-01-01

    Invasive fungal disease (IFD) has high mortality rate, especially in the growing population of immunocompromised patients. In spite of introduction of novel diagnostic approaches, the intravital recognition of IFD is challenging. Autopsy studies remain a key tool for assessment of epidemiology of visceral mycoses. We aimed to determine species distribution and trends of IFD over the last 10 years in unselected autopsy series from a large university hospital. Forty-five cases of visceral mycoses, confirmed by histopathology and panfungal PCR, were found in 587 consecutive autopsies. Major underlying diseases were diabetes mellitus (20%), hematologic malignancies (15.6%) and systemic lupus erythematosus (15.6%). There was a high risk for disseminated IFD in immunocompromised patients stayed in the hospital over 1 month with a fever longer than 3 weeks. The most common fungi were Aspergillus spp. (58%), Candida spp. (16%), Mucorales (14%) and Fusarium spp. (10%). We found significant increase in Aspergillus flavus (P = 0.04) and Mucorales (P < 0.01) infections over the last 5 years. Concordance rate between histopathology and panfungal PCR was 89.5% to the genus level. All 6 cases of fusariomycosis were misinterpreted as aspergillosis by histology alone. The precise species identification, necessary for targeted antifungal treatment, was rendered only by the molecular technique. Panfungal PCR showed high performance on formalin-fixed paraffin-embedded specimens, providing important epidemiological data in retrospective autopsy series. Rapid detection of fungi by panfungal PCR assay has high potential for intravital diagnostics of IFD in surgical and biopsy specimens. PMID:26823814

  18. 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. PMID:24631738

  19. 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

  20. Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study

    PubMed Central

    Mutschlechner, Wolfgang; Aigner, Maria; Grif, Katharina; Marth, Claudia; Girschikofsky, Michael; Grander, Wilhelm; Greil, Richard; Russ, Gudrun; Cerkl, Peter; Eller, Mirjam; Kropshofer, Gabriele; Eschertzhuber, Stephan; Kathrein, Hermann; Schmid, Stefan; Beer, Ronny; Lorenz, Ingo; Theurl, Igor; Nachbaur, David

    2013-01-01

    Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the “gold standard.” In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of 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. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests. PMID:23269732

  1. Application of the 1,3-β-D-Glucan (Fungitell) Assay in the Diagnosis of Invasive Fungal Infections.

    PubMed

    Tran, Tuan; Beal, Stacy G

    2016-02-01

    With the high mortality rate associated with invasive fungal infections, methods for timely detection and diagnosis are necessary for appropriate and effective treatment. Testing for 1,3-β-D-glucan, a cell wall component of many medically important fungi, can be a useful adjunct in diagnosing such infections. The Fungitell assay (Associates of Cape Cod, East Falmouth, Massachusetts) is a US Food and Drug Administration-approved laboratory test that quantitatively measures 1,3-β-D-glucan levels and is widely available for clinical use as a relatively noninvasive method to aid in detecting the presence of invasive fungal infections. Numerous studies have evaluated its performance in clinical settings, and results have, overall, been favorable. It is not without its drawbacks, however, and the test must be interpreted and applied with care. Ordering practices are also widely variable among clinicians, and official guidelines have not been readily available. We present the details of this test and aim to propose evidence-based guidance for its use. PMID:26910223

  2. Invasion of the Central Nervous System by Cryptococcus neoformans Requires a Secreted Fungal Metalloprotease

    PubMed Central

    Vu, Kiem; Tham, Rick; Uhrig, John P.; Thompson, George R.; Na Pombejra, Sarisa; Jamklang, Mantana; Bautos, Jennifer M.

    2014-01-01

    ABSTRACT Cryptococcus spp. cause life-threatening fungal infection of the central nervous system (CNS), predominantly in patients with a compromised immune system. Why Cryptococcus neoformans has this remarkable tropism for the CNS is not clear. Recent research on cerebral pathogenesis of C. neoformans revealed a predominantly transcellular migration of cryptococci across the brain endothelium; however, the identities of key fungal virulence factors that function specifically to invade the CNS remain unresolved. Here we found that a novel, secreted metalloprotease (Mpr1) that we identified in the extracellular proteome of C. neoformans (CnMpr1) is required for establishing fungal disease in the CNS. Mpr1 belongs to a poorly characterized M36 class of fungalysins that are expressed in only some fungal species. A strain of C. neoformans lacking the gene encoding Mpr1 (mpr1Δ) failed to breach the endothelium in an in vitro model of the human blood-brain barrier (BBB). A mammalian host infected with the mpr1Δ null strain demonstrated significant improvement in survival due to a reduced brain fungal burden and lacked the brain pathology commonly associated with cryptococcal disease. The in vivo studies further indicate that Mpr1 is not required for fungal dissemination and Mpr1 likely targets the brain endothelium specifically. Remarkably, the sole expression of CnMPR1 in Saccharomyces cerevisiae resulted in a robust migration of yeast cells across the brain endothelium, demonstrating Mpr1’s specific activity in breaching the BBB and suggesting that Mpr1 may function independently of the hyaluronic acid-CD44 pathway. This distinct role for Mpr1 may develop into innovative treatment options and facilitate a brain-specific drug delivery platform. PMID:24895304

  3. 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. PMID:17356853

  4. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections.

    PubMed

    Pickering, Jerry W; Sant, Howard W; Bowles, Catherine A P; Roberts, William L; Woods, Gail L

    2005-12-01

    The Fungitell assay (Associates of Cape Cod, Inc.) is a commercial test that detects (1-3)-beta-D-glucan (BG) and is intended for diagnosis of invasive fungal infections. To evaluate the Fungitell assay, we tested serum and plasma samples from healthy blood donors and from patients with blood cultures positive for yeast or bacteria. All 36 blood donors were BG negative, and 13 of 15 candidemic patients were BG positive. Of 25 bacteremic patients, 14 (10 with gram-positive bacteremia) were BG positive. One of the latter patients with Staphylococcus aureus bacteremia also had invasive candidiasis, based on histological findings in a tissue biopsy; therefore, the BG result was a true positive. The sensitivity, specificity, and positive and negative predictive values of the Fungitell assay, by patient, for these three groups were 93.3%, 77.2%, 51.9%, and 97.8%, respectively. We also performed the Fungitell assay on sera that had been tested for Aspergillus galactomannan or Histoplasma antigen. All six Histoplasma antigen-positive patients and 31 of 32 Aspergillus galactomannan-positive patients were also BG positive. BG results for the 10 Histoplasma antigen-negative and the 32 Aspergillus galactomannan-negative patients varied, but we were unable to confirm many of the results. Between-run coefficients of variance (CVs) for the assay ranged from 3.2% to 16.8%; within-run CVs were < or =4.8%. The correlation coefficient for an interlaboratory reproducibility study was 0.9892. Concentrations of hemoglobulin, bilirubin, and triglycerides that caused 20% interference were 588, 72, and 466 mg/dl, respectively. Our results suggest that the Fungitel assay may be most useful for excluding invasive fungal infection. PMID:16333082

  5. Localized Production of Phytoalexins by Peanut (Arachis hypogaea) Kernels in Response to Fungal Invasion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peanuts respond to fungal infection by synthesizing phytoalexins, most of which are antibiotic stilbenes. The mechanism and dynamics of phytoalexin formation in the peanut has not been studied. One of the most popular peanut cultivars in the southeastern U.S., Georgia Green, was investigated for its...

  6. 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

  7. 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. PMID:24597227

  8. Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

    PubMed Central

    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

    2014-01-01

    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.) PMID:25049247

  9. 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

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

    PubMed

    Drummond, Rebecca A; Collar, Amanda L; 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

    2015-12-01

    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

  11. Clinical utility of panfungal polymerase chain reaction for the diagnosis of invasive fungal disease: a single center experience.

    PubMed

    Trubiano, J A; Dennison, A M; Morrissey, C O; Chua, K Y; Halliday, C L; Chen, S C-A; Spelman, D

    2016-02-01

    The role of panfungal polymerase chain reaction (PCR) assays for diagnosis of invasive fungal disease (IFD) is inadequately defined. We describe the use of an internal transcribed spacer 1 (ITS-1) region-directed panfungal PCR in this context at a tertiary referral transplant center. A retrospective review of patients at Alfred Health, Melbourne, Australia (2009-2014) who had clinical samples referred for panfungal PCR testing was conducted. Baseline patient characteristics, antifungal drug history, fungal culture/histopathology, and radiology results were recorded. For bronchoalveolar lavage (BAL) fluid samples, identification of a fungus other than a Candida spp. was defined as a potential pathogen.Of 138 panfungal PCR tests (108 patients), 41 (30%) were positive for a fungal product. Ninety-seven percent (134/138) of specimens were from immunocompromised hosts. Thirteen percent (19/138) of panfungal PCR positive results were for potential pathogens and potential pathogens were detected more frequently in tissue as compared with BAL (12/13 vs. 6/26; P = .0001). No positive panfungal PCR results were obtained from CSF specimens. If histopathology examination was negative, panfungal PCR identified a potential pathogen in only 12% (11/94) of specimens. For the 20 culture negative/histopathology positive specimens, diagnosis of IFD to causative species level by panfungal PCR occurred in 35% (6/20).Sterile site specimens, in particular tissue, were more frequently panfungal PCR positive for potential pathogens than BAL. The utility of panfungal PCR appears greatest in tissue specimens, as an adjunct to histopathology to improve diagnostic sensitivity and specificity. Based on the results of this study we are now only testing tissue specimens by panfungal PCR. PMID:26527638

  12. New fungal pathogens of the red ant, Myrmica rubra, from the UK and implications for ant invasions in the USA.

    PubMed

    Evans, Harry C; Groden, Eleanor; Bischoff, Joseph F

    2010-01-01

    The red ant, Myrmica rubra, is an increasingly invasive pest species in north-eastern USA, where it is known as the European fire ant. During surveys for natural enemies in part of its native range in the UK, three previously unreported fungal pathogens developed on ants when incubated in the laboratory. These are described and illustrated: Paraisaria myrmicarum sp. nov., Hirsutella stilbelliformis var. myrmicarum var. nov., and Hirsutella subramanianii var. myrmicarum var. nov. Based on analyses of the protein coding region EF-1α and LSU rDNA, all three described taxa are shown to be affiliated with the hypocrealean family Ophiocordycipitaceae. The implications for the management of M. rubra in its exotic North American range using classical biological control are discussed. PMID:20943156

  13. Contribution of the (1-->3)-beta-D-glucan assay for diagnosis of invasive fungal infections.

    PubMed

    Persat, Florence; Ranque, Stéphane; Derouin, Francis; Michel-Nguyen, Annie; Picot, Stéphane; Sulahian, Annie

    2008-03-01

    Diagnosis of invasive fungal infection (IFI) remains a challenge. A retrospective study was performed on 279 patients at three French university hospitals to evaluate the performance of the (1-->3)-beta-D-glucan assay (BG assay; Fungitell; Associates of Cape Cod, Inc.) for the diagnosis of IFI. The results of one serum per subject were analyzed for 117 patients who had probable or proven IFI according to the European Organization for Research and Treatment of Cancer criteria (70 invasive pulmonary aspergilloses [IPA], 27 fungal bloodstream infections, and 20 Pneumocystis jiroveci pneumonias), 40 blood donors, and 122 patients who were hospitalized in hematology wards or intensive care units and were at risk for IFI but in whom IFI had not been diagnosed. For the overall IFI diagnosis, the BG assay had 77.8% sensitivity and specificities of 92.5 and 70.5% for blood donors and patients at risk, respectively. The assay was positive in 48 patients with IPA (68%), in 23 with bloodstream infections (85.2%), and in all who had P. jiroveci pneumonias (100%), and the false-positive rate varied depending on the controls used. It allowed a higher rate of detection among IPA patients compared to the galactomannan enzyme-linked immunosorbent assay (ELISA) (48 versus 39 patients, respectively) and among candidemia patients compared to the mannan ELISA (20 versus 11 patients, respectively). This assay therefore appears to be useful in the diagnosis of IFI, particularly for serum analysis of pneumocystosis pneumonia patients, but further studies are needed to evaluate false-positive rates and its future role in IFI diagnosis. PMID:18160456

  14. β-d-Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Koltze, Antonia; Rath, Peter; Schöning, Stefan; Steinmann, Jörg; Wichelhaus, Thomas A.; Bader, Peter; Bochennek, Konrad

    2015-01-01

    While the assessment of β-d-glucan (BDG) levels in adults improves the early diagnosis of invasive fungal disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and Candida sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (<30%). Receiver operating characteristic analyses suggested an optimal cutoff between 60 and 70 pg/ml for different definitions of the onset of IFD. Our data show that BDG screening in pediatric HSCT recipients has a low positive predictive value and is therefore of limited usefulness. PMID:26041896

  15. 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

  16. 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

  17. 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.). PMID:27185799

  18. 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. PMID:26054703

  19. Evaluation of a Commercially Developed Semiautomated PCR–Surface-Enhanced Raman Scattering Assay for Diagnosis of Invasive Fungal Disease

    PubMed Central

    Hibbitts, Samantha J.; Perry, Michael D.; Green, Julie; Stirling, Emma; Woodford, Luke; McNay, Graeme; Stevenson, Ross; Barnes, Rosemary A.

    2014-01-01

    Nonculture-based tests are gaining popularity in the diagnosis of invasive fungal disease (IFD), but PCR is excluded from disease-defining criteria because of limited standardization and a lack of commercial assays. Commercial PCR assays may have a standardized methodology while providing quality assurance. The detection of PCR products by a surface-enhanced Raman scattering (SERS) assay potentially provides superior analytical sensitivity and multiplexing capacity compared to that of real-time PCR. Using this approach, the RenDx Fungiplex assay was developed to detect Candida and Aspergillus. Analytical and clinical evaluations of the assay were undertaken using extraction methods according to European Aspergillus PCR Initiative (EAPCRI) recommendations. A total of 195 previously extracted samples (133 plasma, 49 serum, and 13 whole blood) from 112 patients (29 with proven/probable IFD) were tested. The 95% limit of detection of Candida and Aspergillus was 200 copies per reaction, with an overall reproducibility of 92.1% for detecting 20 input copies per PCR, and 89.8% for the nucleic acid extraction–PCR-SERS process for detecting fungal burdens of <20 genome equivalents per sample. A clinical evaluation showed that assay positivity significantly correlated with IFD (P < 0.0001). The sensitivity of the assay was 82.8% and was similar for both Candida (80.0%) and Aspergillus (85.7%). The specificity was 87.5% and was increased (97.5%) by using a multiple (≥2 samples) PCR-positive threshold. In summary, the RenDx Fungiplex assay is a PCR-SERS assay for diagnosing IFD and demonstrates promising clinical performance on a variety of samples. This was a retrospective clinical evaluation, and performance is likely to be enhanced through a prospective analysis of clinical validity and by determining clinical utility. PMID:25031443

  20. Evaluation of a commercially developed semiautomated PCR-surface-enhanced raman scattering assay for diagnosis of invasive fungal disease.

    PubMed

    White, P Lewis; Hibbitts, Samantha J; Perry, Michael D; Green, Julie; Stirling, Emma; Woodford, Luke; McNay, Graeme; Stevenson, Ross; Barnes, Rosemary A

    2014-10-01

    Nonculture-based tests are gaining popularity in the diagnosis of invasive fungal disease (IFD), but PCR is excluded from disease-defining criteria because of limited standardization and a lack of commercial assays. Commercial PCR assays may have a standardized methodology while providing quality assurance. The detection of PCR products by a surface-enhanced Raman scattering (SERS) assay potentially provides superior analytical sensitivity and multiplexing capacity compared to that of real-time PCR. Using this approach, the RenDx Fungiplex assay was developed to detect Candida and Aspergillus. Analytical and clinical evaluations of the assay were undertaken using extraction methods according to European Aspergillus PCR Initiative (EAPCRI) recommendations. A total of 195 previously extracted samples (133 plasma, 49 serum, and 13 whole blood) from 112 patients (29 with proven/probable IFD) were tested. The 95% limit of detection of Candida and Aspergillus was 200 copies per reaction, with an overall reproducibility of 92.1% for detecting 20 input copies per PCR, and 89.8% for the nucleic acid extraction-PCR-SERS process for detecting fungal burdens of <20 genome equivalents per sample. A clinical evaluation showed that assay positivity significantly correlated with IFD (P < 0.0001). The sensitivity of the assay was 82.8% and was similar for both Candida (80.0%) and Aspergillus (85.7%). The specificity was 87.5% and was increased (97.5%) by using a multiple (≥ 2 samples) PCR-positive threshold. In summary, the RenDx Fungiplex assay is a PCR-SERS assay for diagnosing IFD and demonstrates promising clinical performance on a variety of samples. This was a retrospective clinical evaluation, and performance is likely to be enhanced through a prospective analysis of clinical validity and by determining clinical utility. PMID:25031443

  1. Reduction in incidence of invasive fungal infection in patients receiving allogeneic stem cell transplantation using combined diagnostic-driven approach and itraconazole oral solution.

    PubMed

    Tzadok, Roie; Shapira, Michael Y; Moses, Allon E; Or, Reuven; Block, Colin; Strahilevitz, Jacob

    2015-12-01

    Invasive fungal infections are an important cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation. We evaluated, in our allogeneic stem cell transplant patients, the effect on the incidence of invasive fungal infection during neutropenia of a strategy combining a diagnostic-driven approach with chemoprophylaxis during higher risk periods of graft vs. host disease and prolonged neutropenia, using itraconazole oral solution with parenteral voriconazole bridging. One hundred and thirty patients admitted for allogeneic stem cell transplantation within two predefined 20 month periods were included in the study. Data for all patients were collected prospectively. Implementation of the protocol resulted in the administration of more prophylactic antifungals to more patients. Following implementation, there was a non-significant decrease in the overall number of invasive fungal infections (IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2 of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not significantly affected. A combined diagnostic-driven approach and antifungal prophylaxis with oral itraconazole and an intravenous voriconazole bridging protocol, was associated with a reduced, albeit non-statistically significant, number of IFI in our medical centre. PMID:26429354

  2. Prophylaxis of invasive aspergillosis with voriconazole or caspofungin during building work in patients with acute leukemia

    PubMed Central

    Chabrol, Amélie; Cuzin, Lise; Huguet, Françoise; Alvarez, Muriel; Verdeil, Xavier; Linas, Marie Denise; Cassaing, Sophie; Giron, Jacques; Tetu, Laurent; Attal, Michel; Récher, Christian

    2010-01-01

    Background Invasive aspergillosis is a common life-threatening infection in patients with acute leukemia. The presence of building work near to hospital wards in which these patients are cared for is an important risk factor for the development of invasive aspergillosis. This study assessed the impact of voriconazole or caspofungin prophylaxis in patients undergoing induction chemotherapy for acute leukemia in a hematology unit exposed to building work. Design and Methods This retrospective cohort study was carried out between June 2003 and January 2006 during which building work exposed patients to a persistently increased risk of invasive aspergillosis. This study compared the cumulative incidence of invasive aspergillosis in patients who did or did not receive primary antifungal prophylaxis. The diagnosis of invasive aspergillosis was based on the European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria. Results Two-hundred and fifty-seven patients (213 with acute myeloid leukemia, 44 with acute lymphocytic leukemia) were included. The mean age of the patients was 54 years and the mean duration of their neutropenia was 21 days. Eighty-eight received antifungal prophylaxis, most with voriconazole (n=74). The characteristics of the patients who did or did not receive prophylaxis were similar except that pulmonary antecedents (chronic bronchopulmonary disorders or active tobacco use) were more frequent in the prophylaxis group. Invasive aspergillosis was diagnosed in 21 patients (12%) in the non-prophylaxis group and four (4.5%) in the prophylaxis group (P=0.04). Pulmonary antecedents, neutropenia at diagnosis and acute myeloid leukemia with high-risk cytogenetics were positively correlated with invasive aspergillosis, whereas primary prophylaxis was negatively correlated. Survival was similar in both groups. No case of zygomycosis was observed. The 3-month mortality rate was 28% in patients with invasive aspergillosis. Conclusions

  3. 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. PMID:26709146

  4. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies

    PubMed Central

    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

    2016-01-01

    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. PMID:26910891

  5. 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 Central

    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.

    2009-01-01

    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. PMID:18637757

  6. 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

  7. 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

  8. Invasive fungal infections in patients with hematologic malignancies (aurora project): lights and shadows during 18-months surveillance.

    PubMed

    Montagna, Maria Teresa; De Giglio, Osvalda; Napoli, Christian; Lovero, Grazia; Caggiano, Giuseppina; Delia, Mario; Pastore, Domenico; Santoro, Nicola; Specchia, Giorgina

    2012-01-01

    The aim of this multicenter prospective study was to evaluate the incidence of invasive fungal infections (IFIs) in adult and pediatric patients with hematologic malignancies, involving nine nosocomial facilities in Southern Italy over a period of 18 months. Furthermore, results of an environmental microbial surveillance routinely carried out in some of the enrolled hospitals are reported. A total of 589 onco-hematological patients were enrolled and 27 IFIs were documented. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 2.7% and 1.9%, respectively). The yeasts were mainly represented by Candida spp. (87.5%), all isolated by blood cultures; C. parapsilosis was the most common species. Among mould infections, the most frequent site was the lung, with regard to aspergillosis (81.8%). In six of the 10 patients with suspected aspergillosis, the diagnosis was made by the detection of galactomannan and (1,3)-β-d-glucan antigens. The microbiological surveillance carried out on 156 air, 312 water and 312 surface samples revealed low environmental contamination: Alternaria alternata was the only fungus isolated from two surface samples. Our data, especially the low occurrence of filamentous fungi, suggest a particular local epidemiology. Further studies are needed to confirm this microbiological trend in onco-hematological patients in Southern Italy, the results of which might be helpful to improve the management of these patients. PMID:22312285

  9. Quantifying the associations between fungal endophytes and biocontrol-induced herbivory of invasive purple loosestrife (Lythrum salicaria L.).

    PubMed

    David, Aaron S; Quiram, Gina L; Sirota, Jennie I; Seabloom, Eric W

    2016-01-01

    Fungal endophytes are one of several groups of heterotrophic organisms that associate with living plants. The net effects of these groups of organisms on each other and ultimately on their host plants depend in part on how they facilitate or antagonize one another. In this study we quantified the associations between endophyte communities and herbivory induced by a biological control in the invasive Lythrum salicaria at various spatial scales using a culture-based approach. We found positive associations between herbivory damage and endophyte isolation frequency and richness at the site level and weak, positive associations at the leaf level. Herbivory damage was more strongly influenced by processes at the site level than were endophyte isolation frequency and community structure, which were influenced by processes at the plant and leaf levels. Furthermore, endophytic taxa found in low herbivory sites were nested subsets of those taxa found at high herbivory sites. Our findings suggest that endophyte communities of L. salicaria are associated with, and potentially facilitated by, biocontrol-induced herbivory. Quantifying the associations between heterotrophic groups ultimately may lead to a clearer understanding of their complex interactions with plants. PMID:27091387

  10. A Critical Appraisal of the Role of the Clinical Microbiology Laboratory in Diagnosis of Invasive Fungal Infections

    PubMed Central

    Klutts, J. Stacey; Robinson-Dunn, Barbara

    2011-01-01

    The incidence of invasive fungal infections (IFIs) continues to rise in industrialized countries, primarily due to both increasingly potent iatrogenic immunosuppression and immunocompromising therapies aimed at treating hematologic malignancies. As this situation continues to evolve, the clinical microbiology laboratory has few new, innovative methodologies to diagnose these serious infections and existing methods lack sensitivity. This represents a difficult clinical situation for health care providers, as they are left to rely on clinical instincts for the management of patients with potential IFIs, as mycology test results are not consistently reliable. The goals of this session of Camp Clin Micro (CCM) were to critically assess currently available methods and practices for diagnosing IFIs, to discuss the potential of current investigational methods, to evaluate the role of antifungal susceptibility testing, and finally to identify action items that can help move the field of diagnostic mycology in a direction that will improve our ability to identify IFIs in a timely manner. This is meant to be not a comprehensive overview of the diagnosis of IFIs but rather a detailed account of the discussion at CCM among clinical microbiologists with experience in diagnostic mycology and knowledge of the literature.

  11. Invasive Fungal Infections in Patients with Hematologic Malignancies (Aurora Project): Lights and Shadows During 18-Months Surveillance

    PubMed Central

    Montagna, Maria Teresa; De Giglio, Osvalda; Napoli, Christian; Lovero, Grazia; Caggiano, Giuseppina; Delia, Mario; Pastore, Domenico; Santoro, Nicola; Specchia, Giorgina

    2012-01-01

    The aim of this multicenter prospective study was to evaluate the incidence of invasive fungal infections (IFIs) in adult and pediatric patients with hematologic malignancies, involving nine nosocomial facilities in Southern Italy over a period of 18 months. Furthermore, results of an environmental microbial surveillance routinely carried out in some of the enrolled hospitals are reported. A total of 589 onco-hematological patients were enrolled and 27 IFIs were documented. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 2.7% and 1.9%, respectively). The yeasts were mainly represented by Candida spp. (87.5%), all isolated by blood cultures; C. parapsilosis was the most common species. Among mould infections, the most frequent site was the lung, with regard to aspergillosis (81.8%). In six of the 10 patients with suspected aspergillosis, the diagnosis was made by the detection of galactomannan and (1,3)-β-d-glucan antigens. The microbiological surveillance carried out on 156 air, 312 water and 312 surface samples revealed low environmental contamination: Alternaria alternata was the only fungus isolated from two surface samples. Our data, especially the low occurrence of filamentous fungi, suggest a particular local epidemiology. Further studies are needed to confirm this microbiological trend in onco-hematological patients in Southern Italy, the results of which might be helpful to improve the management of these patients. PMID:22312285

  12. 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

  13. [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. PMID:24930085

  14. Prospective trial finds nystatin mouthwash effective prophylaxis for pulmonary invasive fungal infections that originate in the throat of patients with hematologic malignancies.

    PubMed

    Hu, R; Jiang, X; Wu, Y

    2013-01-01

    We investigated the source of fungi in the lungs of patients with hematological malignancies who had invasive pulmonary fungal infections (IPFI). We also conducted a prospective study to evaluate the efficacy of different mouthwash solutions in preventing IPFI in patients with hematologic malignancies. In order to determine the source of fungi in the lungs of 30 patients with hematologic malignancies who had IPFI, we collected samples from sites with suspected fungal infection and used PCR and sequencing for pathogen identification. For the prospective study, we enrolled 158 patients with hematological malignancies who had IPFI and randomly assigned them to one of three mouthwash groups: 1% nystatin, 2.5% sodium bicarbonate, or normal saline. Fungal staining and incidence of IPFI, oral fungal infection, and intestinal fungal infection were evaluated. We showed that 96.7% of the fungi isolated from the throats and the lungs were identical; 76.9% of the fungi from the lungs and digestive tracts were identical and, 84.6 % of the fungi from the throats and digestive tract were identical. Patients using 1% nystatin had lower incidence of IPFI (1.6%) and fungal enteritis (1.6%) than those using sodium bicarbonate (16.3% and 14.3%) or normal saline (27.7% and 12.8%). All treatments had low incidences of oral fungal infections (0 to 4.3%). Our data showed that fungi originating from mouth and throat cause IPFI. We also showed that use of a prophylactic mouthwash containing 1% nystatin was effective in preventing IPFI in patients with hematological malignancies. PMID:23374002

  15. Effect of Early Screening for Invasive Fungal Infections in U.S. Service Members with Explosive Blast Injuries

    PubMed Central

    Weintrob, Amy C.; Rodriguez, Carlos; Dunne, James R.; Weisbrod, Allison B.; Hinkle, Mary; Warkentien, Tyler; Murray, Clinton K.; Oh, John; Millar, Eugene V.; Shah, Jinesh; Shaikh, Faraz; Gregg, Stacie; Lloyd, Gina; Stevens, Julie; Carson, M. Leigh; Aggarwal, Deepak; Tribble, David R.

    2014-01-01

    Abstract Background: An outbreak of invasive fungal infections (IFI) began in 2009 among United States servicemen who sustained blast injuries in Afghanistan. In response, the military trauma community sought a uniform approach to early diagnosis and treatment. Toward this goal, a local clinical practice guideline (CPG) was implemented at Landstuhl Regional Medical Center (LRMC) in early 2011 to screen for IFI in high-risk patients using tissue histopathology and fungal cultures. Methods: We compared IFI cases identified after initiation of the CPG (February through August 2011) to cases from a pre-CPG period (June 2009 through January 2011). Results: Sixty-one patients were screened in the CPG period, among whom 30 IFI cases were identified and compared with 44 pre-CPG IFI cases. Demographics between the two study periods were similar, although significantly higher transfusion requirements (p<0.05) and non-significant trends in injury severity scores and early lower extremity amputation rates suggested more severe injuries in CPG-period cases. Pre-CPG IFI cases were more likely to be associated with angioinvasion on histopathology than CPG IFI cases (48% versus 17%; p<0.001). Time to IFI diagnosis (three versus nine days) and to initiation of antifungal therapy (seven versus 14 days) were significantly decreased in the CPG period (p<0.001). Additionally, more IFI patients received antifungal agent at LRMC during the CPG period (30%) versus pre-CPG period (5%; p=0.005). The CPG IFI cases were also prescribed more commonly dual antifungal therapy (73% versus 36%; p=0.002). There was no statistical difference in length of stay or mortality between pre-CPG and CPG IFI cases; although a non-significant reduction in crude mortality from 11.4% to 6.7% was observed. Conclusions: Angioinvasive IFI as a percentage of total IFI cases decreased during the CPG period. Earlier diagnosis and commencement of more timely treatment was achieved. Despite these improvements, no

  16. Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis

    PubMed Central

    Neofytos, Dionysios; Railkar, Radha; Mullane, Kathleen M.; Fredricks, David N.; Granwehr, Bruno; Marr, Kieren A.; Almyroudis, Nikolaos G.; Kontoyiannis, Dimitrios P.; Maertens, Johan; Fox, Rebecca; Douglas, Cameron; Iannone, Robert; Kauh, Eunkyung; Shire, Norah

    2015-01-01

    Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA). We examined whether early changes in serum galactomannan (GM) and/or β-D-glucan (BDG) can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GM and BDG levels and GM optical density indices (GMI) were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2% (25/47) and 65.9% (27/41) had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03) and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02). Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05; GMI, P = 0.03) and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01). Overall survival rates at 6 weeks and 12 weeks were 87.2% (41/47) and 79.1% (34/43), respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01; GM, P = 0.03) and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007). Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA. PMID:26107507

  17. Economic evaluation of a preemptive treatment strategy for invasive fungal infection in neutropenic patients with hematological diseases.

    PubMed

    Kimura, S-I; Murata, T; Akahoshi, Y; Nakano, H; Ugai, T; Wada, H; Yamasaki, R; Ishihara, Y; Kawamura, K; Sakamoto, K; Ashizawa, M; Sato, M; Terasako-Saito, K; Nakasone, H; Kikuchi, M; Yamazaki, R; Kako, S; Kanda, J; Tanihara, A; Nishida, J; Kanda, Y

    2015-05-01

    We compared the expected medical costs of empirical and preemptive treatment strategies for invasive fungal infection in neutropenic patients with hematological diseases. Based on the results of two clinical trials with different backgrounds reported by Oshima et al. [J Antimicrob Chemother 60(2):350-355; Oshima study] and Cordonnier et al. [Clin Infect Dis 48(8):1042-1051; PREVERT study], we developed a decision tree model that represented the outcomes of empirical and preemptive treatment strategies, and estimated the expected medical costs of medications and examinations in the two strategies. We assumed that micafungin was started in the empirical group at 5 days after fever had developed, while voriconazole was started in the preemptive group only when certain criteria, such as positive test results of imaging studies and/or serum markers, were fulfilled. When we used an incidence of positive test results of 6.7 % based on the Oshima study, the expected medical costs of the empirical and preemptive groups were 288,198 and 150,280 yen, respectively. Even in the case of the PREVERT study, in which the incidence of positive test results was 32.9 %, the expected medical costs in the empirical and preemptive groups were 291,871 and 284,944 yen, respectively. A sensitivity analysis indicated that the expected medical costs in the preemptive group would exceed those in the empirical group when the incidence of positive test results in the former was over 34.4 %. These results suggest that a preemptive treatment strategy can be expected to reduce medical costs compared with empirical therapy in most clinical settings. PMID:25577175

  18. Randomized Trial of Micafungin for the Prevention of Invasive Fungal Infection in High-Risk Liver Transplant Recipients

    PubMed Central

    Saliba, Faouzi; Pascher, Andreas; Cointault, Olivier; Laterre, Pierre-François; Cervera, Carlos; De Waele, Jan J.; Cillo, Umberto; Langer, Róbert M.; Lugano, Manuela; Göran-Ericzon, Bo; Phillips, Stephen; Tweddle, Lorraine; Karas, Andreas; Brown, Malcolm; Fischer, Lutz; Pratschke, Johann; Decruyenaere, Johan; De Waele, Jan J.; Laterre, Pierre-François; Moreno, Christophe; Michielsen, Peter; Cointault, Olivier; Fischer, Lutz; Neuhaus, Peter; Pascher, Andreas; Schemmer, Peter; Cervera, Carlos; Varo, Evaristo; Montejo, Miguel; Bouza, Emilio; Blanes, Marino; De La Torre, Julián; Fortun, Jesus; Saliba, Faouzi; Rostaing, Lionel; Paugam-Burtz, Catherine; Eyraud, Daniel; Shah, Tahir; Heaton, Nigel; Langer, Róbert M.; McCormick, Aiden; Cillo, Umberto; Salizzoni, Mauro; Lugano, Manuela; De Gasperi, Andrea; Tomé, Luís; Daniel, Jorge; Popescu, Irinel; Moysyuk, Yan G.; Chzhao, Alexey V.; Zagaynov, Vladimir E.; Ericzon, Bo-Göran

    2015-01-01

    Background. Invasive fungal infection (IFI) following liver transplant is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk. Methods. In this open-label, noninferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) posttransplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Noninferiority (10% margin) of micafungin vs standard care was assessed in the per protocol and full analysis sets. Safety assessments included adverse events and liver and kidney function tests. Results. The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At EOP (mean treatment duration, 17 days), clinical success was 98.6% for micafungin and 99.3% for standard care (Δ standard care – micafungin [95% confidence interval], 0.7% [−2.7% to 4.4%]) in the per protocol set and 96.5% and 93.6%, respectively (−2.9% [−8.0% to 1.9%]), in the full analysis set. Incidences of drug-related adverse events for micafungin and standard care were 11.6% and 16.3%, leading to discontinuation in 6.4% and 11.6% of cases, respectively. At EOP, liver function tests were similar but creatinine clearance was higher in micafungin- vs standard care–treated patients. Conclusions. Micafungin was noninferior to standard care as antifungal prophylaxis in liver transplant patients at high risk for IFI. Adverse event profiles and liver function at EOP were similar, although kidney function was better with micafungin. Clinical Trials Registration. NCT01058174. PMID:25520332

  19. 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

    2016-01-01

    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

  20. 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.

  1. Identification of invasive fungal diseases in immunocompromised patients by combining an Aspergillus specific PCR with a multifungal DNA-microarray from primary clinical samples.

    PubMed

    Boch, T; Reinwald, M; Postina, P; Cornely, O A; Vehreschild, J J; Heußel, C P; Heinz, W J; Hoenigl, M; Eigl, S; Lehrnbecher, T; Hahn, J; Claus, B; Lauten, M; Egerer, G; Müller, M C; Will, S; Merker, N; Hofmann, W-K; Buchheidt, D; Spiess, B

    2015-12-01

    The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy. PMID:26497302

  2. Pulmonary fungal infections in patients with acute myeloid leukaemia: is it the time to revise the radiological diagnostic criteria?

    PubMed

    Maccioni, Francesca; Vetere, Simone; De Felice, Carlo; Al Ansari, Najwa; Micozzi, Alessandra; Gentile, Giuseppe; Foà, Robin; Girmenia, Corrado

    2016-06-01

    The definition of pulmonary fungal infections (PFI) according to the EORTC-MSG criteria may lack diagnostic sensitivity due to the possible presentation of PFI with different radiological pictures. We evaluated the hypothesis to apply less restrictive radiological criteria to define PFI in patients with acute myeloid leukaemia (AML) submitted to chemotherapy. Overall, 73 consecutive episodes of pulmonary infiltrates associated to positive serum galactomannan test or fungal isolation or galactomannan detection from respiratory specimens were considered. CT scans acquired at the onset of symptoms (time-0) and within 4 weeks (time-1) were analysed to identify specific (group A) or aspecific radiological signs (group B). Pulmonary infiltrates fulfilled the EORTC-MSG criteria in 49 patients (group A), whereas in 24 patients (group B) they did not reach the criteria due to aspecific CT findings at time-0. Eleven of 21 (52.4%) patients of the group B evaluable for the evolution of the radiological findings fulfilled EORTC-MSG criteria at time-1. All the analysed clinical and mycological characteristics, response to antifungal therapy and survival were comparable in the two groups. Our study seems to confirm the possibility to extend the radiological suspicion of PFI to less restrictive chest CT findings when supported by microbiological criteria in high-risk haematological patients. PMID:26865204

  3. 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

  4. 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. PMID:18975486

  5. Fungal arthritis

    MedlinePlus

    ... and irritation (inflammation) of a joint by a fungal infection. It is also called mycotic arthritis. Causes Fungal ... symptoms of fungal arthritis. Prevention Thorough treatment of fungal infections elsewhere in the body may help prevent fungal ...

  6. 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

  7. Development of a GFP-Expressing Aspergillus flavus Strain to Study Fungal Invasion, Colonization, and Resistance in Cottonseed

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton bolls were inoculated with a green fluorescent protein (GFP)-expressing Aspergillus flavus (strain 70) to monitor fungal growth, mode of entry, colonization of cottonseeds and production of aflatoxins. The GFP strain and the wild type did not differ significantly in pathogen aggressiveness a...

  8. Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

    PubMed Central

    Johnson, S Peter; Ramasawmy, Rajiv; Campbell-Washburn, Adrienne E; Wells, Jack A; Robson, Mathew; Rajkumar, Vineeth; Lythgoe, Mark F; Pedley, R Barbara; Walker-Samuel, Simon

    2016-01-01

    Background: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503. Methods: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2* MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg−1 OXi4503. Results: A significant decrease in SW1222 tumour perfusion was observed (−43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R2* in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits. Conclusions: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting. PMID:27031853

  9. Non-invasive ventilation in immunocompromised patients with acute hypoxemic respiratory failure

    PubMed Central

    Del Sorbo, Lorenzo; Jerath, Angela; Dres, Martin

    2016-01-01

    The survival rate of immunocompromised patients has improved over the past decades in light of remarkable progress in diagnostic and therapeutic options. Simultaneously, there has been an increase in the number of immunocompromised patients with life threatening complications requiring intensive care unit (ICU) treatment. ICU admission is necessary in up to 15% of patients with acute leukemia and 20% of bone marrow transplantation recipients, and the main reason for ICU referral in this patient population is acute hypoxemic respiratory failure, which is associated with a high mortality rate, particularly in patients requiring endotracheal intubation. The application of non-invasive ventilation (NIV), and thus the avoidance of endotracheal intubation and invasive mechanical ventilation with its side effects, appears therefore of great importance in this patient population. Early trials supported the benefits of NIV in these settings, and the 2011 Canadian guidelines for the use of NIV in critical care settings suggest the use of NIV in immune-compromised patients with a grade 2B recommendation. However, the very encouraging results from initial seminal trials were not confirmed in subsequent observational and randomized clinical studies, questioning the beneficial effect of NIV in immune-compromised patients. Based on these observations, a French group led by Azoulay decided to assess whether early intermittent respiratory support with NIV had a role in reducing the mortality rate of immune-compromised patients with non-hypercapnic hypoxemic respiratory failure developed in less than 72 h, and hence conducted a multicenter randomized controlled trial (RCT) in experienced ICUs in France. This perspective reviews the findings from their RCT in the context of the current critical care landscape, and in light of recent results from other trials focused on the early management of acute hypoxemic respiratory failure. PMID:27076972

  10. 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

  11. Randomized, double-blind trial of anidulafungin versus fluconazole for prophylaxis of invasive fungal infections in high-risk liver transplant recipients.

    PubMed

    Winston, D J; Limaye, A P; Pelletier, S; Safdar, N; Morris, M I; Meneses, K; Busuttil, R W; Singh, N

    2014-12-01

    Invasive fungal infections (IFIs) are a common complication in liver transplant recipients. There are no previous randomized trials of an echinocandin for the prevention of IFIs in solid organ transplant recipients. In a randomized, double-blind trial conducted at University-affiliated transplant centers, 200 high-risk liver transplant recipients (100 patients per group) received either anidulafungin or fluconazole for antifungal prophylaxis. Randomization was stratified by Model for End-Stage Liver Disease score ≥30 and receipt of a pretransplant antifungal agent. The primary end point was IFI in a modified intent-to-treat analysis. The overall incidence of IFI was similar for the anidulafungin (5.1%) and the fluconazole groups (8.0%) (OR 0.61, 95% CI 0.19-1.94, p = 0.40). However, anidulafungin prophylaxis was associated with less Aspergillus colonization or infection (3% vs. 9%, p = 0.08), lower breakthrough IFIs among patients who had received pretransplant fluconazole (0% vs. 27%, p = 0.07), and fewer cases of antifungal resistance (no cases vs. 5 cases). Both drugs were well-tolerated. Graft rejection, fungal-free survival, and mortality were similar for both groups. Thus, anidulafungin and fluconazole have similar efficacy for antifungal prophylaxis in most liver transplant recipients. Anidulafungin may be beneficial if the patient has an increased risk for Aspergillus infection or received fluconazole before transplantation. PMID:25376267

  12. Rhabdomyolysis and acute renal failure following minimally invasive spine surgery: report of 5 cases.

    PubMed

    Dakwar, Elias; Rifkin, Stephen I; Volcan, Ildemaro J; Goodrich, J Allan; Uribe, Juan S

    2011-06-01

    Minimally invasive spine surgery is increasingly used to treat various spinal pathologies with the goal of minimizing destruction of the surrounding tissues. Rhabdomyolysis (RM) is a rare but known complication of spine surgery, and acute renal failure (ARF) is in turn a potential complication of severe RM. The authors report the first known case series of RM and ARF following minimally invasive lateral spine surgery. The authors retrospectively reviewed data in all consecutive patients who underwent a minimally invasive lateral transpsoas approach for interbody fusion with the subsequent development of RM and ARF at 2 institutions between 2006 and 2009. Demographic variables, patient home medications, preoperative laboratory values, and anesthetic used during the procedure were reviewed. All patient data were recorded including the operative procedure, patient positioning, postoperative hospital course, operative time, blood loss, creatine phosphokinase (CPK), creatinine, duration of hospital stay, and complications. Five of 315 consecutive patients were identified with RM and ARF after undergoing minimally invasive lateral transpsoas spine surgery. There were 4 men and 1 woman with a mean age of 66 years (range 60-71 years). The mean body mass index was 31 kg/m2 and ranged from 25 to 40 kg/m2. Nineteen interbody levels had been fused, with a range of 3-6 levels per patient. The mean operative time was 420 minutes and ranged from 315 to 600 minutes. The CPK ranged from 5000 to 56,000 U/L, with a mean of 25,861 U/L. Two of the 5 patients required temporary hemodialysis, while 3 required only aggressive fluid resuscitation. The mean duration of the hospital stay was 12 days, with a range of 3-25 days. Rhabdomyolysis is a rare but known potential complication of spine surgery. The authors describe the first case series associated with the minimally invasive lateral approach. Surgeons must be aware of the possibility of postoperative RM and ARF, particularly in

  13. Fungal infection intensity and zoospore output of Atelopus zeteki, a potential acute chytrid supershedder.

    PubMed

    Direnzo, Graziella V; Langhammer, Penny F; Zamudio, Kelly R; Lips, Karen R

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t50 = 7.018, p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially as they relate to

  14. Fungal Infection Intensity and Zoospore Output of Atelopus zeteki, a Potential Acute Chytrid Supershedder

    PubMed Central

    DiRenzo, Graziella V.; Langhammer, Penny F.; Zamudio, Kelly R.; Lips, Karen R.

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t50 = 7.018, p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially

  15. Acute Chiasmal Abscess Resulting from Perineural Extension of Invasive Sino-Orbital Aspergillosis in an Immunocompetent Patient

    PubMed Central

    Leyngold, Ilya; Olivi, Alessandro; Ishii, Masaru; Blitz, Ari; Burger, Peter; Subramanian, Prem S.; Gallia, Gary

    2015-01-01

    OBJECTIVE Intracranially invasive sino-orbital aspergillosis is a rare entity seen predominantly in immunocompromised individuals. We report a unique case of an acute chiasmal abscess resulting from perineural extension of an indolent invasive sino-orbital aspergillosis in an immunocompetent patient. CASE DESCRIPTION A 61-year-old healthy Ukrainian man presented with severe left retro-orbital pain and a gradual ipsilateral monocular vision loss with rapid progression to a contralateral temporal visual field cut. He was found to have an intracranially invasive sino-orbital Aspergillus fumigatus infection with perineural extension along the optic nerve complicated by an acute chiasmal abscess. RESULTS The patient was managed with surgical debridement and adjuvant antifungal chemotherapy. The patient’s life and vision were preserved. CONCLUSIONS The case demonstrates that it is possible to successfully control advanced intracranial aspergillosis with tissue-sparing surgery and adjuvant antifungal chemotherapy in immunocompetent individuals. PMID:23973515

  16. Underuse of invasive procedures among Medicaid patients with acute myocardial infarction.

    PubMed Central

    Philbin, E F; McCullough, P A; DiSalvo, T G; Dec, G W; Jenkins, P L; Weaver, W D

    2001-01-01

    OBJECTIVES: The purpose of this study was to determine whether underuse of cardiac procedures among Medicaid patients with acute myocardial infarction is explained by or is independent of fundamental differences in age, race, or sex distribution; income, coexistent illness; or location of care. METHODS: Administrative data from 226 hospitals in New York were examined for 11,579 individuals hospitalized with a primary diagnosis of acute myocardial infarction. Use of various cardiac procedures was compared among Medicaid patients and patients with other forms of insurance. RESULTS: Medicaid patients were older, were more frequently African American and female, and had lower median household incomes. They also had a higher prevalence of hypertension, diabetes, lung disease, renal disease, and peripheral vascular disease. After adjustment for these and other factors, Medicaid patients were less likely to undergo cardiac catheterization, percutaneous transluminal coronary angioplasty, and any revascularization procedure. CONCLUSIONS: Factors other than age, race, sex, income, coexistent illness, and location of care account for lower use of invasive procedures among Medicaid patients. The influence of Medicaid insurance on medical practice and process of care deserves investigation. PMID:11441735

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

    PubMed

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

    2016-04-01

    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

  18. 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. PMID:24438353

  19. The (1,3){beta}-D-glucan test as an aid to early diagnosis of invasive fungal infections following lung transplantation.

    PubMed

    Alexander, Barbara D; Smith, P Brian; Davis, R Duane; Perfect, John R; Reller, L Barth

    2010-11-01

    The Fungitell assay for (1,3)β-D-glucan (BG) detection in serum has been evaluated in patients with invasive fungal infections (IFIs) and healthy controls and for the early diagnosis of IFI in cancer patients. We evaluated the BG assay for the detection of IFI in lung transplant recipients. Serial serum samples were prospectively collected from patients undergoing lung transplants at Duke Hospital. Fungal infections were classified according to revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. A receiver operator characteristic (ROC) curve was generated; possible causes for false-positive and false-negative tests were investigated by linear regression analysis. Seven hundred fifty-six serum specimens from 59 subjects without IFI and 41 specimens from 14 patients with proven or probable IFI were tested. The area under the ROC curve was 0.69. Based on a 60-pg/ml positive cutoff, per-patient sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 64%, 9%, 14%, and 50%, respectively; per-test estimates were 71%, 59%, 9%, and 97%, respectively. The majority (92%) of patients not diagnosed with an IFI had at least one BG level of ≥60 pg/ml, and 90% had at least one BG level of ≥80 pg/ml. Respiratory colonization with mold and hemodialysis significantly affected mean BG levels. In conclusion, the accuracy of the BG test is marginal and its utility as a tool for the early diagnosis of IFI is questionable in the lung transplant population. Although the NPV of the BG test is high, the low PPV limits its utility as a screening tool for early diagnosis of IFI. PMID:20720025

  20. Does ampicillin-sulbactam cause false positivity of (1,3)-beta-D-glucan assay? A prospective evaluation of 15 patients without invasive fungal infections.

    PubMed

    Metan, Gokhan; Agkus, Cigdem; Nedret Koc, A; Elmali, Ferhan; Finkelman, Malcolm A

    2012-07-01

    The purpose of this study was to investigate the interaction between intravenous ampicillin-sulbactam treatment and (1,3)-beta-D-glucan (BDG) assay. Fifteen patients with a median age of 60 (16-81) without known risk factors for invasive fungal infections who received a daily dose of 3×2g ampicillin-sulbactam monotherapy from different batches were included in the study. Thirteen patients had soft tissue infections. The 5 of 13 patients who went under surgery had surgical dressings. Serum samples were obtained both before and after antibiotic infusion on the first, third, seventh and tenth days of an ampicillin-sulbactam treatment course. BDG was assayed using the Fungitell kit (Associates of Cape Cod, East Falmouth, MA, USA) according to manufacturers' specifications. All serum samples were also tested for galactomannan (GM) antigenemia by Platelia Aspergillus ELISA (Bio-Rad Laboratories, Marnes-la-Coquette, France). A total of 37 of 117 serum samples were positive for BDG at a threshold of 80pg ml(-1) . Seven of 37 BDG positive serum samples had a GM index ≥0.5. When a cutoff value of ≥0.5 was used for GM positivity, 16 (13.3%) serum samples were positive. For a cutoff value of ≥0.7, eight (6.6%) serum samples were positive. There were no statistically significant differences in the median BDG levels (P=0.47) or median GM indices (P =0.28) of the various sampling times. None of the SAM vials tested positive for BDG or GM. After ruling out fungal infections and all known potential causes of false BDG positivity, environmental contamination remained possible cause of BDG reactivity. We did not observe any significant association of ampicillin-sulbactam administration and positive assays for BDG or GM. PMID:22040530

  1. The impacts of invaders: basal and acute stress glucocorticoid profiles and immune function in native lizards threatened by invasive ants.

    PubMed

    Graham, Sean P; Freidenfelds, Nicole A; McCormick, Gail L; Langkilde, Tracy

    2012-05-01

    As anthropogenic stressors increase exponentially in the coming decades, native vertebrates will likely face increasing threats from these novel challenges. The success or failure of the primary physiological mediator of these stressors--the HPA axis--will likely involve numerous and chaotic outcomes. Among the most challenging of these new threats are invasive species. These have the capacity to simultaneously challenge the HPA axis and the immune system as they are often associated with, or the cause of, emerging infectious diseases, and energetic tradeoffs with the HPA response can have immunosuppressive effects. To determine the effects of invasive species on the vertebrate GC response to a novel stressor, and on immunity, we examined the effects of invasive fire ants on native lizards, comparing lizards from sites with long histories with fire ants to those outside the invasion zone. We demonstrated higher baseline and acute stress (captive restraint) CORT levels in lizards from within fire ant invaded areas; females are more strongly affected than males, suggesting context-specific effects of invasion. We found no effect of fire ant invasion on the immune parameters we measured (complement bacterial lysis and antibody hemagglutination) with the exception of ectoparasite infestation. Mites were far less prevalent on lizards within fire ant invaded sites, suggesting fire ants may actually benefit lizards in this regard. This study suggests that invasive species may impose physiological stress on native vertebrates, but that the consequences of this stress may be complicated and unpredictable. PMID:22226759

  2. 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

  3. Early interventional therapy for acute massive pulmonary embolism guided by minimally invasive hemodynamic monitoring

    PubMed Central

    Wang, Lihua; Xu, Yi; Zhang, Weiwen; Lu, Wei; Chen, Meiqin; Luo, Jian

    2015-01-01

    Aim: The aim of this study was to investigate the clinical significance of minimally invasive hemodynamic monitoring in the early catheter-based intervention for acute massive pulmonary embolism (PE). Methods: A total of 40 cases with acute massive PE were randomized into experimental and control group with 20 cases in each group. In the experimental group, the hemodynamics was monitored via Vigileo/FloTrac system, while echocardiography was used in the control group. Twelve hours after systemic thrombolysis, catheter-based clot fragmentation and local thrombolysis were employed in the experimental group if Vigileo/FloTrac system revealed hemodynamic abnormality. For the control group, the application of catheter was determined by the findings in echocardiography at 24 hours after systemic thrombolysis. Results: A total of 12 cases in the experimental group underwent catheter therapy successfully while 4 cases in the control group received the same treatment. Compared to the control group, 12 hours after catheter intervention the experimental group had higher PaO2/FIO2 and right ventricular ejection fraction (RVEF) but lower pulmonary artery systolic pressure (PASP), indicating the effectiveness of Vigileo/FloTrac monitoring. The 28-day survival rates were identical between the groups although one patent in the control group died. Both the RVEF and PASP were significantly improved in the experimental group in 6 months compared to the control group. Conclusions: In massive PE, hemodynamic monitoring via Vigileo/FloTrac system might be useful in the decision making for catheter intervention after systemic thrombolysis and might improve the outcomes for patients. PMID:26550360

  4. Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis.

    PubMed

    Tsitsikas, Dimitris A; Morin, Amelie; Araf, Shamzah; Murtagh, Bernadine; Johnson, Gemma; Vinnicombe, Sarah; Ellis, Stephen; Suaris, Tamara; Wilks, Mark; Doffman, Sarah; Agrawal, Samir G

    2012-07-01

    Diagnosis of invasive aspergillosis (IA) remains a challenge as the clinical manifestations are not specific, and a histological diagnosis is often unfeasible. The 2002 European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria for classification of cases into possible, probable or proven were revised in 2008. Our objective was to analyze the impact of these revisions on the diagnosis of IA. A retrospective analysis of 589 high risk patient-episodes revealed that 125 of 155 'possible' (81%) and 12 of 16 'probable' (75%) cases of IA should be changed to 'non-classifiable' when the new criteria were applied. We concluded, as expected, that the 2008 EORTC/MSG revised definitions reduced the number of cases classified as 'possible' IA, but additionally, there has been a dramatic reduction in 'probable' cases. These changes have significant implications on the interpretation of clinical trial data based on EORTC/MSG classifications. PMID:22074309

  5. Routine pre-and post-hematopoietic stem cell transplant computed tomography of the abdomen for detecting invasive fungal infection has limited value

    PubMed Central

    Kaste, Sue C.; Kaufman, Robert A.; Sunkara, Anusha; Kang, Guolian; Morris, Cynthia; Leung, Wing; Srinivasan, Ashok

    2015-01-01

    The diagnostic utility of obtaining chest and abdomen CT evaluating for invasive fungal infection (IFI) pre-and post-HSCT remains unclear. The study was conducted as a Quality Improvement project. Chest and abdomen CT of patients who underwent an allogeneic HSCT over a 13 month period were reviewed. Scans included those done pre-transplant in all patients, and day 0–100 post-transplant in selected patients. There were 66 patients with chest and abdomen CT scans pre-transplant. Chest CT was suggestive of IFI in 9 (13.6%) patients including 3 patients with prior history of IFI. After transplant, 37 patients had initial chest CT, and 14 patients had initial abdominal CT. The first chest CT post-transplant was suggestive of IFI in 3 patients; all had an abnormal CT pre-transplant. Following the initial post-transplant evaluation 15 patients had 28 additional CT scans of the chest, and 12 patients had 19 additional CT scans of the abdomen. An abnormal chest CT with proven evidence of IFI was seen in only one patient. None of the 99 abdominal CT scans performed pre-or post-transplant had evidence of IFI. There is little benefit in obtaining abdominal CT scans in HSCT patients for detecting IFI either pre-or post-transplant. PMID:25748273

  6. Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections.

    PubMed

    Wang, Taotao; Zhu, Huifang; Sun, Jinyao; Cheng, Xiaoliang; Xie, Jiao; Dong, Haiyan; Chen, Limei; Wang, Xue; Xing, Jianfeng; Dong, Yalin

    2014-11-01

    The aim of this study was to determine an optimum voriconazole target concentration, to study the influence of CYP2C19 gene status on metabolism of voriconazole and to identify a dose-adjustment strategy for voriconazole according to CYP2C19 polymorphism in patients with invasive fungal infections. A total of 328 voriconazole trough plasma concentrations (C(min)) were collected and monitored from 144 patients. Information on efficacy and safety was obtained. Voriconazole therapy was effective in 81.9% of patients (118/144), and 12.5% (18/144) exhibited signs of hepatotoxicity. The relationships between voriconazole C(min) and clinical response and hepatotoxicity were explored using logistic regression, and a target clinical C(min) range of 1.5-4 mg/L was identified. Values of voriconazole C(min) and the ratio of C(min) to concentration of voriconazole-N-oxide (C(min)/C(N)) of poor metabolisers (PMs) were significantly higher than extensive metabolisers and intermediate metabolisers. Model-based simulations showed that PM patients could be safely and effectively treated with 200 mg twice daily orally or intravenously, and non-PM patients with 300 mg twice daily orally or 200mg twice daily intravenously. This study highlighted that voriconazole C(min) and C(min)/C(N) are strongly influenced by CYP2C19 polymorphism, and gene-adjusted dosing is important to achieve therapeutic levels that maximise therapeutic response and minimise hepatotoxicity. PMID:25239277

  7. Routine pre- and post-hematopoietic stem cell transplant computed tomography of the abdomen for detecting invasive fungal infection has limited value.

    PubMed

    Kaste, Sue C; Kaufman, Robert A; Sunkara, Anusha; Kang, Guolian; Morris, Cynthia; Leung, Wing; Srinivasan, Ashok

    2015-06-01

    The diagnostic utility of obtaining chest and abdomen computed tomography (CT) to evaluate for invasive fungal infection (IFI) before and after hematopoietic stem cell transplant (HSCT) remains unclear. The study was conducted as a quality improvement project. Chest and abdomen CT of patients who underwent an allogeneic HSCT over a 13-month period were reviewed. Scans included those performed pretransplant in all patients and days 0 to 100 post-transplant in selected patients. Sixty-six patients had chest and abdomen CT scans pretransplant. Chest CT was suggestive of IFI in 9 patients (13.6%), including 3 patients with prior history of IFI. After transplant, 37 patients had an initial chest CT and 14 patients an initial abdominal CT. The first chest CT post-transplant was suggestive of IFI in 3 patients; all had an abnormal CT pretransplant. After the initial post-transplant evaluation, 15 patients had 28 additional CT scans of the chest and 12 patients 19 additional CT scans of the abdomen. An abnormal chest CT with proven evidence of IFI was seen in only 1 patient. None of the 99 abdominal CT scans performed pre- or post-transplant had evidence of IFI. There is little benefit in obtaining abdominal CT scans in HSCT patients for detecting IFI either pre- or post-transplant. PMID:25748273

  8. 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

    2016-02-01

    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. PMID:26723514

  9. The Screening Performance of Serum 1,3-Beta-D-Glucan in Patients with Invasive Fungal Diseases: A Meta-Analysis of Prospective Cohort Studies

    PubMed Central

    Hou, Tie-Ying; Wang, Shou-Hong; Liang, Sui-Xin; Jiang, Wen-Xin; Luo, Dan-Dong; Huang, De-Hong

    2015-01-01

    The serum 1,3-beta-D-glucan (BG) assay aids in the early diagnosis of invasive fungal diseases (IFDs) and has been approved for their diagnosis. However, reports on the screening performance of BG are scarce. We performed a meta-analysis of data extracted from only prospective cohort studies to evaluate the screening performance of the BG assay in the diagnosis of IFDs. We specifically searched 4 databases (the PubMed, Web of Science, Elsevier, and Cochrane Collaboration databases) according to EORTC-MSG criteria. A total of 1068 patients in 11 studies were analyzed. Deeks’ funnel plot asymmetry test suggested a low likelihood of publication bias for the included studies (p = 0.055). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve, with 95% confidence intervals, were 0.75(0.63,0.84), 0.87(0.81,0.92), 5.85(3.96,8.63), 0.30(0.20,0.45), 19.53(11.16,34.18), and 0.89(0.86,0.91), respectively. The findings of this meta-analysis suggest that the BG assay is a useful screening tool with high sensitivity and specificity for discriminating between patients with and without IFDs. In clinical practice, BG assay results should be evaluated together with clinical and microbiological findings. PMID:26146829

  10. Epidemiology and treatment of invasive fungal diseases in patients with multiple myeloma: findings from a multicenter prospective study from China.

    PubMed

    Liu, Junru; Huang, He; Li, Yan; Liu, Lin; Li, Jianyong; Liu, Zhuogang; Lu, Jin; Ouyang, Jian; Song, Yongping; Zhou, Daobin; Ren, Hanyun; Ma, Jun; Wang, Chun; Yu, Li; Zhou, Jin; Wang, Jianmin; Xiao, Yang; Huang, Xiaojun; Li, Juan

    2016-06-01

    The aim of this study is to investigate the epidemiology, diagnosis, treatment and risk factors of multiple myeloma patients with invasive fungi disease (IFD) in China. We analyzed multiple myeloma (MM) patients receiving chemotherapy in a prospective multicenter study. Basic characteristics, the diagnosis, and treatment of IFD were recorded. A total of 395 MM patients were enrolled, who received a total of 443 chemotherapy courses. Among them, 17 IFDs were diagnosed during one chemotherapy course. Fourteen of these were possible IFD and 3 were probable IFD. Ten of the 14 patients with possible IFD had lung infection. Thirty eight (8.6 %) patients received antifungal prophylaxis, and 47.4 % of them were administered with fluconazole. Patients who had a history of IFD or underwent a combined therapy with two antibiotics for over 7 days and with a history of granulocytopenia or ductus venosus insertion were more likely to be treated with antifungal prophylaxis. All of first-line antifungal therapies were monotherapy. Eleven (84.6 %) cases were treated with azoles. The median time of initial antifungal therapy was 8 days. The general condition of two patients with probable IFD and 10 patients (90.9 %) with possible IFD improved, while 1 patient with possible IFD died. Multivariate analysis revealed that history of IFD is an independent risk factor of IFD. The present multicenter study suggests that the incidence of IFD per chemotherapy courses in MM patients is 3.8 % and most patients are labelled as having possible IFD. Fluconazole is the most common antifungal agent for prophylaxis and voriconazole for therapeutic treatment. Previous IFD is a probable independent risk factor of IFD in MM patients receiving chemotherapy. PMID:26700667

  11. Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis

    PubMed Central

    Ribeiro, Laura R. R.; Loures, Flávio V.; de Araújo, Eliseu F.; Feriotti, Cláudia; Costa, Tânia A.; Serezani, Carlos Henrique; Jancar, Sonia; Calich, Vera L. G.

    2015-01-01

    Cysteinyl leukotrienes (CysLTs) and lipoxins (LXs) are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J) and susceptible (B10.A) mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages. PMID:26635449

  12. Immunotherapy of Fungal Infections.

    PubMed

    Datta, Kausik; Hamad, Mawieh

    2015-11-01

    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. PMID:26575463

  13. Gastrointestinal Zygomycosis Masquerading as Acute Appendicitis

    PubMed Central

    Choi, Won-Tak; Chang, Tammy T.; Gill, Ryan M.

    2016-01-01

    Zygomycosis is a rare invasive opportunistic fungal infection that occurs in the setting of hematologic malignancies, chemotherapy-induced neutropenia, and immunosuppressive therapies. We report the first case of disseminated appendiceal zygomycosis due to Absidia spp. in a neutropenic patient who initially presented as acute appendicitis. A 63-year-old woman with acute myeloid leukemia presented as acute appendicitis while receiving induction chemotherapy and ultimately succumbed to overwhelming disseminated zygomycosis. Initial symptoms included loose stools and right lower abdominal pain unresponsive to broad-spectrum antibiotics. Clinical examination and cross-sectional imaging suggested acute appendicitis. The final diagnosis was established by histological evaluations of the ileocecectomy specimen, which showed angioinvasive fungal organisms within the necrotic appendiceal wall with characteristics typical of zygomycetes. Fungal cultures demonstrated Absidia spp. The patient was treated with amphotericin B but expired in the setting of fungal sepsis. A diagnosis of a fungal infection, including zygomycosis, should be considered in all chemotherapy-induced neutropenic patients who present with symptoms of acute appendicitis. A high index of clinical suspicion with prompt histologic and culture diagnosis of zygomycosis may reduce the high mortality and morbidity associated with zygomycosis of the gastrointestinal tract. PMID:27403107

  14. Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis.

    PubMed

    Montesinos, P; Rodríguez-Veiga, R; Boluda, B; Martínez-Cuadrón, D; Cano, I; Lancharro, A; Sanz, J; Arilla, M J; López-Chuliá, F; Navarro, I; Lorenzo, I; Salavert, M; Pemán, J; Calvillo, P; Martínez, J; Carpio, N; Jarque, I; Sanz, G F; Sanz, M A

    2015-11-01

    Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment. PMID:26281032

  15. 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. PMID:27161786

  16. A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia.

    PubMed

    Rozenberg-Arska, M; Dekker, A W; Branger, J; Verhoef, J

    1991-03-01

    In a prospective randomized study the efficacy of fluconazole (50 mg in one single daily dose) was compared with oral amphotericin B in suspension and tablets (each 200 mg four times daily) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia. All patients received ciprofloxacin for prevention of bacterial infections. Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease (one documented and one highly suspected infection in each group of patients). Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract. Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4% in the amphotericin B group (P less than 0.01). Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole. PMID:2037541

  17. Fungal Tests

    MedlinePlus

    ... effectiveness of treatment. For many superficial skin and yeast infections, a clinical examination of the affected person ... the chemical solution dissolves non-fungal elements; reveals yeast cells and fungal hyphae (branching filaments) on a ...

  18. Incidence of invasive aspergillosis following remission–induction chemotherapy for acute leukemia: a retrospective cohort study in a single Canadian tertiary care centre

    PubMed Central

    Barkati, Sapha; Dufresne, Simon F.; Bélanger, Sylvie; Vadnais, Barbara; Bergeron, Julie; Labbé, Annie Claude

    2014-01-01

    Background The decision to use universal primary antimould prophylaxis to prevent invasive aspergillosis in patients with acute leukemia depends on the incidence of infection at individual centres. We determined our institution’s incidence of invasive aspergillosis among patients who received remission–induction chemotherapy for acute leukemia to evaluate the potential benefits of primary antimould prophylaxis. Methods We conducted this retrospective cohort study at a Canadian tertiary care centre. From the central pharmacy registries, we retrieved records for all adult patients for whom remission–induction chemotherapy for acute leukemia was prescribed between 2008 and 2010. We retrieved clinical, microbiologic, pathologic and radiologic data from the patients’ medical charts. The primary outcome was a diagnosis of probable or proven invasive aspergillosis up to 180 days after resolution of aplasia. Results We retrieved records for 123 patients with acute leukemia. Twenty-two of these patients did not receive the prescribed chemotherapy and were excluded from the analysis. Of the 101 patients included, 77 (76.2%) had acute myeloid leukemia. Overall, 136 courses of chemotherapy were administered, with more than 1 course administered to 26 (25.7%) of the 101 patients. In 9 of the patients (8.9%; 95% confidence interval 4.2%–16.2%), invasive aspergillosis was diagnosed (3 proven and 6 probable cases) a median of 19 (range 11–34) days after initiation of chemotherapy. In 7 (78%) of these 9 patients, invasive aspergillosis occurred during the first course of chemotherapy. Three patients died within the first year after diagnosis of invasive aspergillosis. Interpretation We found a high incidence (8.9%) of invasive aspergillosis at our centre. This finding triggered the introduction of targeted antimould prophylaxis for patients with acute leukemia who were undergoing remission–induction chemotherapy. PMID:25077134

  19. Invasive aspergillosis in near drowning nonneutropenic patient

    PubMed Central

    Munta, Kartik; Gopal, Palepu B. N.; Vigg, Ajit

    2015-01-01

    Invasive aspergillosis in immunosuppressed people has been well documented, but to diagnose and treat in an immunocompetent individual after near drowning, it requires early suspicion and proper empirical treatment. We report a case diagnosed to have invasive aspergillosis with systemic dissemination of the infection to the brain, gluteal muscles, and kidneys after a fall in a chemical tank of a paper manufacturing company. He was ventilated for acute respiratory distress syndrome and managed with antibiotics and vasopressors. Due to nonresolving pneumonia and positive serum galactomannan, trans-tracheal biopsy was performed which confirmed invasive aspergillosis and was treated with antifungals. With the availability of galactomannan assay and better radiological investigative modalities, occurrence of such invasive fungal infections in cases of drowning patients should be considered early in such patients and treated with appropriate antifungals. PMID:26816451

  20. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-β-D-glucan for invasive fungal infection: Focus on cutoff levels.

    PubMed

    He, Song; Hang, Ju-Ping; Zhang, Ling; Wang, Fang; Zhang, De-Chun; Gong, Fang-Hong

    2015-08-01

    To assess the diagnostic accuracy of 1,3-β-D-glucan (BDG) assay for diagnosing invasive fungal infections (IFI), we searched the Medline and Embase databases, and studies reporting the performance of BDG assays for the diagnosis of IFI were identified. Our analysis was mainly focused on the cutoff level. Meta-analysis was performed using conventional meta-analytical pooling and bivariate analysis. Our meta-analysis covered 28 individual studies, in which 896 out of 4214 patients were identified as IFI positive. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic (AUC-SROC) curve were 0.78 [95% confidence interval (CI), 0.75-0.81], 0.81 (95% CI, 0.80-0.83), 21.88 (95% CI, 12.62-37.93), and 0.8855, respectively. Subgroup analyses indicated that in cohort studies, the cutoff value of BDG at 80 pg/mL had the best diagnostic accuracy, whereas in case-control studies the cutoff value of 20 pg/mL had the best diagnostic accuracy; moreover, the AUC-SROC in cohort studies was lower than that in case-control studies. The cutoff value of 60 pg/mL has the best diagnostic accuracy with the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria as a reference standard. The 60 pg/mL cutoff value has the best diagnostic accuracy with the Fungitell assay compared to the BDG detection assay. The cutoff value of 20 pg/mL has the best diagnostic accuracy with the Fungitec G-test assay, and the cutoff value of 11 pg/mL has the best diagnostic accuracy with the Wako assay. Serum BDG detection is highly accurate for diagnosing IFIs. As such, 60 pg/mL of BDG level can be used as the best cutoff value to distinguish patients with IFIs from patients without IFI (mainly due to Candida and Aspergillus). PMID:25081986

  1. 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

  2. Non-invasive measurement of pulmonary blood flow during prone positioning in patients with early acute respiratory distress syndrome.

    PubMed

    Reutershan, Jörg; Schmitt, Andre; Dietz, Klaus; Fretschner, Reinhold

    2004-01-01

    In the daily clinical routine at the bedside, information on effective pulmonary blood flow (PBF) is limited and requires invasive monitoring, including a pulmonary artery catheter, to determine both cardiac output and intrapulmonary shunt. Therefore we evaluated a non-invasive method for the measurement of PBF in a clinical setting, including 12 patients with acute respiratory failure (acute respiratory distress syndrome) undergoing prone positioning. PBF was determined before (baseline), during and after prone positioning, by using a foreign gas rebreathing method with a new photoacoustic gas analyser. Values were compared with the cardiac output corrected for intrapulmonary shunt (COeff). Responders to prone positioning were defined according to the improvement of arterial oxygenation. A total of 84 measurements were performed. PBF values correlated well with COeff (R2=0.96; P<0.0001). Bias and limits of agreement (+/- 2 S.D.) for all measurements were -0.11 +/- 0.76 litre/min. At baseline, responders showed significantly lower PBF levels than non-responders (4.8 +/- 1.0 compared with. 6.4 +/- 1.2 litre/min; P=0.03). During prone positioning, PBF increased continuously in responders and remained high after patients had been returned to the supine position. PBF was unaffected in non-responders. Mean total increase in PBF was 1.2 +/- 0.2 litre/min in responders compared with -0.4 +/- 0.2 litre/min in non-responders (P<0.0001). In conclusion, the investigated rebreathing system allows for a non-invasive determination of PBF at the bedside. The accuracy of the measurements is comparable with the thermodilution method. It is able to reliably reflect changes in PBF induced by prone positioning. Moreover, measuring PBF might be a promising tool to identify responders to prone therapy. PMID:12877652

  3. 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

  4. Clinical viability of Fungitell, a new (1→3)-β-D: -glucan measurement kit, for diagnosis of invasive fungal infection, and comparison with other kits available in Japan.

    PubMed

    Yoshida, Koichiro; Shoji, Hisashi; Takuma, Takahiro; Niki, Yoshihito

    2011-08-01

    Fungitell, a (1→3)-β-D: -glucan (β-D: -glucan) measurement kit, was approved in the United States in 2004. Three other kits for measurement of β-D: -glucan, Fungitec G test MK (G-MK), β-Glucan test Wako (Wako), and β-Glucan test Maruha (Maruha), are commonly used for diagnosis of invasive fungal diseases in Japan. We evaluated the clinical viability of the Fungitell kit and compared it with the 3 kits generally used in Japan. The plasma β-D: -glucan values measured with each kit showed some differences, possibly because different β-D: -glucan standards, blood pretreatment methods, and kinds of horseshoe crab (a raw material for the main reagent) are used in each kit. Measures of diagnostic efficiency, for example the sensitivity, specificity, and positive and negative predictive values, varied among the kits. Although the areas under the receiver operating characteristic curves of the kits were not significantly different, the sensitivity of the Fungitell kit was the highest, followed by that of the G-MK kit. The sensitivity of the Wako and Maruha kits was low, but the specificity of these tests was higher than that of the G-MK or Fungitell kits. These inconsistent β-D: -glucan measurements could interfere with diagnosis of invasive fungal infection. Early establishment of an international standard method for measurement of β-D: -glucan is required. PMID:21210174

  5. 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

  6. Yeast Identification Algorithm Based on Use of the Vitek MS System Selectively Supplemented with Ribosomal DNA Sequencing: Proposal of a Reference Assay for Invasive Fungal Surveillance Programs in China

    PubMed Central

    Zhang, Li; Xiao, Meng; Wang, He; Gao, Ran; Fan, Xin; Brown, Mitchell; Gray, Timothy J.; Kong, Fanrong

    2014-01-01

    Sequence analysis of the internal transcribed spacer (ITS) region was employed as the gold standard method for yeast identification in the China Hospital Invasive Fungal Surveillance Net (CHIF-NET). It has subsequently been found that matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is potentially a more practical approach for this purpose. In the present study, the performance of the Vitek MS v2.0 system for the identification of yeast isolates collected from patients with invasive fungal infections in the 2011 CHIF-NET was evaluated. A total of 1,243 isolates representing 31 yeast species were analyzed, and the identification results by the Vitek MS v2.0 system were compared to those obtained by ITS sequence analysis. By the Vitek MS v2.0 system, 96.7% (n = 1,202) of the isolates were correctly assigned to the species level and 0.2% (n = 2) of the isolates were identified to the genus level, while 2.4% (n = 30) and 0.7% (n = 9) of the isolates were unidentified and misidentified, respectively. After retesting of the unidentified and misidentified strains, 97.3% (n = 1,209) of the isolates were correctly identified to the species level. Based on these results, a testing algorithm that combines the use of the Vitek MS system with selected supplementary ribosomal DNA (rDNA) sequencing was developed and validated for yeast identification purposes. By employing this algorithm, 99.7% (1,240/1,243) of the study isolates were accurately identified with the exception of two isolates of Candida fermentati and one isolate of Cryptococcus gattii. In conclusion, the proposed identification algorithm could be practically implemented in strategic programs of fungal infection surveillance. PMID:24478490

  7. 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.

  8. Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy

    PubMed Central

    Janzon, M; James, S; Cannon, C P; Storey, R F; Mellström, C; Nicolau, J C; Wallentin, L; Henriksson, M

    2015-01-01

    Objective To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. Methods A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. Results Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. Conclusions Treatment of patients with ACS scheduled for 12 months’ non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. Trial registration number NCT000391872. PMID:25227704

  9. Organ Transplant Patients and Fungal Infections

    MedlinePlus

    ... of hospital-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 ...

  10. 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

  11. Development of a non-invasive murine infection model for acute otitis media.

    PubMed

    Stol, K; van Selm, S; van den Berg, S; Bootsma, H J; Blokx, W A M; Graamans, K; Tonnaer, E L G M; Hermans, P W M

    2009-12-01

    Otitis media (OM) is one of the most frequent diseases in childhood, and Streptococcus pneumoniae is among the main causative bacterial agents. Since current experimental models used to study the bacterial pathogenesis of OM have several limitations, such as the invasiveness of the experimental procedures, we developed a non-invasive murine OM model. In our model, adapted from a previously developed rat OM model, a pressure cabin is used in which a 40 kPa pressure increase is applied to translocate pneumococci from the nasopharyngeal cavity into both mouse middle ears. Wild-type pneumococci were found to persist in the middle ear cavity for 144 h after infection, with a maximum bacterial load at 96 h. Inflammation was confirmed at 96 and 144 h post-infection by IL-1beta and TNF-alpha cytokine analysis and histopathology. Subsequently, we investigated the contribution of two surface-associated pneumococcal proteins, the streptococcal lipoprotein rotamase A (SlrA) and the putative proteinase maturation protein A (PpmA), to experimental OM in our model. Pneumococci lacking the slrA gene, but not those lacking the ppmA gene, were significantly reduced in virulence in the OM model. Importantly, pneumococci lacking both genes were significantly more attenuated than the DeltaslrA single mutant. This additive effect suggests that SlrA and PpmA exert complementary functions during experimental OM. In conclusion, we have developed a highly reproducible and non-invasive murine infection model for pneumococcal OM using a pressure cabin, which is very suitable to study pneumococcal pathogenesis and virulence in vivo. PMID:19762437

  12. Adult-onset Invasive Haemophilus influenzae Type f Caused by Acute Lower Leg Cellulitis.

    PubMed

    Usui, Yuko; Kakuta, Risako; Araki, Makoto; Sato, Taigo; Gu, Yoshiaki; Yano, Hisakazu; Taniuchi, Norihide

    2016-01-01

    In Japan, routine Haemophilus influenzae type b (Hib) vaccination began in 2013. Thus, similar to other countries, a strain shift is expected in the near future. We experienced a case of H. influenzae type f (Hif) bacteremia in a 66-year-old man. The primary focus of the infection was the soft tissue of the left lower leg, which is an extremely rare origin in adults. Subsequently, we conducted multilocus sequence typing and identified the strain as sequence type 124, which is the most common invasive strain of Hif worldwide. This case may mark the beginning of an Hif strain shift in Japan. PMID:27374690

  13. 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

  14. 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. PMID:26519805

  15. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection

    PubMed Central

    Valcour, Victor; Chalermchai, Thep; Sailasuta, Napapon; Marovich, Mary; Lerdlum, Sukalaya; Suttichom, Duanghathai; Suwanwela, Nijasri C.; Jagodzinski, Linda; Michael, Nelson; Spudich, Serena; van Griensven, Frits; de Souza, Mark; Kim, Jerome; Ananworanich, Jintanat

    2012-01-01

    Background. Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans. Methods. Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization. Results. HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ–induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS. Conclusions. CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection. PMID:22551810

  16. Pulmonary fungal infections.

    PubMed

    Smith, Jeannina A; Kauffman, Carol A

    2012-08-01

    This review details some of the advances that have been made in the recent decade in the diagnosis, treatment and epidemiology of pulmonary fungal infections. These advances have occurred because of increasing knowledge regarding the fungal genome, better understanding of the structures of the fungal cell wall and cell membrane and the use of molecular epidemiological techniques. The clinical implications of these advances are more rapid diagnosis and more effective and less toxic antifungal agents. For example, the diagnosis of invasive pulmonary aspergillosis, as well as histoplasmosis and blastomycosis, has improved with the use of easily performed antigen detection systems in serum and bronchoalveolar lavage fluid. Treatment of angioinvasive moulds has improved with the introduction of the new azoles, voriconazole and posaconazole that have broad antifungal activity. Amphotericin B is less frequently used, and when used is often given as lipid formulation to decrease toxicity. The newest agents, the echinocandins, are especially safe as they interfere with the metabolism of the fungal cell wall, a structure not shared with humans cells. Epidemiological advances include the description of the emergence of Cryptococcus gattii in North America and the increase in pulmonary mucormycosis and pneumonia due to Fusarium and Scedosporium species in transplant recipients and patients with haematological malignancies. The emergence of azole resistance among Aspergillus species is especially worrisome and is likely related to increased azole use for treatment of patients, but also to agricultural use of azoles as fungicides in certain countries. PMID:22335254

  17. 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

  18. Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function.

    PubMed

    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

  19. Different acute toxicity of fipronil baits on invasive Linepithema humile supercolonies and some non-target ground arthropods.

    PubMed

    Hayasaka, Daisuke; Kuwayama, Naoki; Takeo, Azuma; Ishida, Takanobu; Mano, Hiroyuki; Inoue, Maki N; Nagai, Takashi; Sánchez-Bayo, Francisco; Goka, Koichi; Sawahata, Takuo

    2015-08-01

    Fipronil is one of the most effective insecticides to control the invasive ant Linepithema humile, but its effectiveness has been assessed without considering the genetic differences among L. humile supercolonies. We hypothesized that the susceptibility of the ant to fipronil might differ among supercolonies. If so, dosage and concentration of fipronil may need to be adjusted for effective eradication of each supercolony. The relative sensitivities of four L. humile supercolonies established in Hyogo (Japan) to fipronil baits were examined based on their acute toxicity (48-h LC(50)). Toxicities of fipronil to seven ground arthropods, including four native ant species, one native isopoda, and two cockroaches were also determined and compared to that of L. humile supercolonies using species sensitivity distributions. Marked differences in susceptibility of fipronil were apparent among the supercolonies (P < 0.008), with the 'Japanese main supercolony' (271 μg L(-1)) being five to ten times more sensitive to fipronil than other colonies (1183-2782 μg L(-1)). Toxicities to non-target species (330-2327 μg L(-1)) were in the same range as that of L. humile, and SSDs between the two species groups were not significantly different (t = -1.389, P = 0.180), suggesting that fipronil's insecticidal activity is practically the same for L. humile as for non-target arthropods. Therefore, if the invasive ant is to be controlled using fipronil, this would also affect the local arthropod biodiversity. Only the 'Japanese main supercolony' can be controlled with appropriate bait dosages of fipronil that would have little impact on the other species. PMID:25980487

  20. 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

  1. 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. PMID:27445833

  2. 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. PMID:24793674

  3. Human fungal pathogens: Why should we learn?

    PubMed

    Kim, Jeong-Yoon

    2016-03-01

    Human fungal pathogens that cause invasive infections are hidden killers, taking lives of one and a half million people every year. However, research progress in this field has not been rapid enough to effectively prevent or treat life-threatening fungal diseases. To update recent research progress and promote more active research in the field of human fungal pathogens, eleven review articles concerning the virulence mechanisms and host interactions of four major human fungal pathogens-Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and Histoplasma capsulatum-are presented in this special issue. PMID:26920875

  4. 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. PMID:27353660

  5. Mucormycosis Rhinosinusitis at Diagnosis of Acute Lymphoblastic Leukemia: Diagnostics and Management Challenges in a Low-Middle-income Country.

    PubMed

    Mandegari, Elham; Fu, Ligia; Arambú, Carolina; Montoya, Sandra; Peña, Armando; Johnson, Kyle M; Perfect, John R; Caniza, Miguela A

    2015-04-01

    We present the case of an adolescent with mucor rhinosinusitis diagnosed concomitantly with acute lymphoblastic leukemia at a hospital in Tegucigalpa, Honduras. We also discuss the challenges faced in the dual management of hematologic malignancies and invasive fungal disease in a low-middle-income country, such as access to diagnostics, immunosuppressants, imaging, and antifungals. Despite these shortcomings, the patient was successfully treated for both the diseases. Low-middle-income country hospitals can effectively treat invasive fungal diseases by providing adequate diagnostic and support services, which can improve the outcomes of pediatric cancer patients. PMID:24942033

  6. Potential Roles of Fungal Extracellular Vesicles during Infection.

    PubMed

    Joffe, Luna S; Nimrichter, Leonardo; Rodrigues, Marcio L; Del Poeta, Maurizio

    2016-01-01

    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

  7. 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

  8. Expanding acute care nurse practitioner and clinical nurse specialist education: invasive procedure training and human simulation in critical care.

    PubMed

    Hravnak, Marilyn; Tuite, Patricia; Baldisseri, Marie

    2005-01-01

    Programs educating advanced practice nurses (APNs), including acute care nurse practitioners (ACNPs) and clinical nurse specialists (CNSs) may struggle with the degree to which technical and cognitive skills necessary and unique to the care of critically ill patients should be incorporated within training programs, and the best ways these skills can be synthesized and retained for clinical practice. This article describes the critical care technical skills training mechanisms and use of a High-Fidelity Human Simulation (HFHS) Laboratory in the ACNP and CNS programs at the University of Pittsburgh School of Nursing. The mechanisms for teaching invasive procedures are reviewed including an abbreviated course syllabus and documentation tools. The use of HFHS is discussed as a measure to provide students with technical and cognitive preparation to manage critical incidents. The HFHS Laboratory, scenario development and implementation, and the debriefing process are discussed. Critical care technical skills training and the use of simulation in the curriculum have had a favorable response from students and preceptors at the University of Pittsburgh School of Nursing, and have enhanced faculty's ability to prepare APNs. PMID:15714021

  9. 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

  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. 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 ...

  12. Nonculture Diagnostics in Fungal Disease.

    PubMed

    Powers-Fletcher, Margaret V; Hanson, Kimberly E

    2016-03-01

    Fungal diagnostics that utilize antibody, antigen or nucleic acid detection offer several advantages that supplement traditional culture-based methods. As a group, nonculture assays can help identify patients with invasive fungal infection (IFI) sooner than is possible with culture, are often more sensitive, and can be used to guide early interventions. Challenges associated with these techniques include the possibility for contamination or cross-reactivity as well as the potential for false negative tests. This review summarized the test characteristics and clinical utility of nonculture-based laboratory methods. PMID:26897062

  13. Prevalence and clinical profile of fungal rhinosinusitis

    PubMed Central

    Arumugam, Dayanand; Zacharias, George; Palaninathan, Sengottaiah; Vishwanathan, Ravisankar; Venkatraman, Vaidyanathan

    2016-01-01

    Background: There are only a few landmark studies from the Indian subcontinent on fungal rhinosinusitis. The lack of awareness among clinicians regarding the varying clinical presentations of fungal rhinosinusitis prompted us to undertake this study. Objective: To determine the prevalence, etiologic basis, clinical features, radiologic features, and microscopic features of fungal rhinosinusitis, and to evaluate the various treatment modalities available. Methods: This was a prospective study in which evaluation of 100 patients with chronic rhinosinusitis was done. Specimens collected were subjected to both microbiology and pathologic examination; data collected, including clinical and radiologic features, were analyzed by the Pearson χ2 test and Fisher's exact test. Results: The prevalence of fungal rhinosinusitis in our study was 30% (n = 30). Mucor was the most commonly isolated species (n = 15 [50%]) of fungus. Pathologic examination had a higher sensitivity (76.67%) compared with microbiology tests (50%) in the diagnosis of fungal rhinosinusitis. Fungus ball (n = 14 [46.6%]) was the most prevalent entity in the spectrum of fungal rhinosinusitis. Forty percent of cases (n = 12) were of invasive fungal rhinosinusitis. The prevalence of fungal rhinosinusitis was higher among individuals who were immunocompetent (n = 17 [56.6%]). Of patients who were immunocompromised, 84.6% (n = 11) had mucormycosis. Conclusions: Unilateral involvement of paranasal sinuses was more in favor of fungal etiology. Complications were more common in fungal rhinosinusitis caused by Mucor species. Mucormycosis, a rare clinical entity, in subjects who were immunocompetent, had a high prevalence in our study. PMID:27349695

  14. 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

  15. Novel antifungal drugs against fungal pathogens: do they provide promising results for treatment?

    PubMed

    Gedik, Habip; Şimşek, Funda; Yıldırmak, Taner; Kantürk, Arzu; Arıca, Deniz; Aydın, Demet; Demirel, Naciye; Yokuş, Osman

    2015-06-01

    The febrile neutropenia episodes of hematological patients and their outcomes were evaluated with respect to fungal pathogens and antifungal therapy in this retrospective study. All patients, who were older than 14 years of age and developed at least one neutropenic episode after chemotherapy due to hematological cancer from November 2010 to November 2012, were included into the study. We retrospectively collected demographic, treatment, and survival data of 126 patients with neutropenia and their 282 febrile episodes. The mean Multinational Association for Supportive Care in Cancer score was 17.18 ± 8.27. Systemic antifungal drugs were initiated in 22 patients with 30 culture-proven invasive fungal infections (IFIs), 25 attacks of 19 patients with probable invasive pulmonary aspergillosis (IPA), 42 attacks of 38 patients with possible IPA, and 31 attacks of 30 patients with suspected IFI. Voriconazole (VOR), caspofungin and liposomal amphotericin B were used to treat 72 episodes of 65 patients, 45 episodes of 37 patients and 34 episodes of 32 patients as a first-line therapy, respectively. Unfavorable conditions of our hematology ward are thought to increase the number of cases with invasive pulmonary aspergillosis and VOR use. It should be taken into consideration that increased systemic and per oral VOR usage predisposes patients to colonization and infection with azole-resistant fungal strains. Catheters should be removed in cases where patients' conditions are convenient to remove it. Acute myeloblastic leukemia cases that are more likely to develop invasive fungal infections should be monitored closely for early diagnosis and timely initiation of antifungal drugs which directly correlates with survival rates. PMID:25825558

  16. Fungal Diagnostics

    PubMed Central

    Kozel, Thomas R.; Wickes, Brian

    2014-01-01

    Early diagnosis of fungal infection is critical to effective treatment. There are many impediments to diagnosis such as a diminishing number of clinical mycologists, cost, time to result, and requirements for sensitivity and specificity. In addition, fungal diagnostics must meet the contrasting needs presented by the increasing diversity of fungi found in association with the use of immunosuppressive agents in countries with high levels of medical care and the need for diagnostics in resource-limited countries where large numbers of opportunistic infections occur in patients with AIDS. Traditional approaches to diagnosis include direct microscopic examination of clinical samples, histopathology, culture, and serology. Emerging technologies include molecular diagnostics and antigen detection in clinical samples. Innovative new technologies that use molecular and immunoassay platforms have the potential to meet the needs of both resource-rich and resource-limited clinical environments. PMID:24692193

  17. Detection and Measurement of Fungal Burden in a Guinea Pig Model of Invasive Pulmonary Aspergillosis by Novel Quantitative Nested Real-Time PCR Compared with Galactomannan and (1,3)-β-d-Glucan Detection

    PubMed Central

    Kocmanova, Iva; Racil, Zdenek; Hrncirova, Kristyna; Pospisilova, Sarka; Mayer, Jiri; Najvar, Laura K.; Wiederhold, Nathan P.; Kirkpatrick, William R.; Patterson, Thomas F.

    2012-01-01

    We developed and assessed the diagnostic value of a novel quantitative nested real-time (QNRT) PCR assay targeting the internal transcribed spacer region of ribosomal DNA (rDNA) in a guinea pig model of invasive pulmonary aspergillosis. Groups of 5 immunosuppressed animals that were infected using an aerosol chamber with Aspergillus fumigatus conidia were humanely terminated 1 h postinoculation and at days 3, 5, 7, and 11 postchallenge, and lung tissue, bronchoalveolar lavage (BAL) fluid, whole blood, and serum samples were collected. The QNRT PCR results obtained with the serum and BAL fluid were compared to those achieved with galactomannan and (1→3)-β-d-glucan assays. High fungal burden levels were detected by QNRT PCR in both lung tissue and BAL fluid in all infected animals at each time point, and the sensitivity of each assay in BAL fluid was 100% by day 3 and remained so through the remainder of the study. The sensitivity of detection of fungi in whole blood and serum samples was significantly lower, and some samples remained negative by all three assays despite the advanced stage of the infection. From these data, we can conclude that this novel QNRT PCR method was highly sensitive for the detection of A. fumigatus from different types of samples in this model. In addition, BAL fluid samples appeared to be the most suitable for the early diagnosis of invasive pulmonary aspergillosis. When testing serum, the use of a combination of available assays may increase the possibility of early detection of this opportunistic mycosis. PMID:22189110

  18. Intracranial fungal aneurysm caused by Candida endocarditis.

    PubMed

    Takeda, S; Wakabayashi, K; Yamazaki, K; Miyakawa, T; Arai, H

    1998-01-01

    We describe a 67-year-old man who died 4 days after suffering a subarachnoid hemorrhage. Autopsy revealed a fresh subarachnoid hemorrhage and a ruptured fungal aneurysm near the trifurcation of the right middle cerebral artery. In comparison with 21 previously reported cases in which the fungal aneurysms were proved to be intracranial, the present case had several characteristic features: the causative fungus of the aneurysm was Candida (only one such case has been reported previously). The aneurysm was caused by direct Candida invasion of the arterial wall from the Candida embolus (previously reported aneurysms have been caused by direct invasion of the arterial wall during fungal meningitis). The source of the Candida was endocarditis (the main sources of fungus in previously reported cases have been sinusitis, dental extraction wounds, and some forms of surgery). We describe the features of this rare autopsy case of a ruptured fungal aneurysm caused by Candida originating from endocarditis and review the literature. PMID:9707334

  19. 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.

  20. Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

    PubMed Central

    Girmenia, Corrado; Frustaci, Anna Maria; Gentile, Giuseppe; Minotti, Clara; Cartoni, Claudio; Capria, Saveria; Trisolini, Silvia Maria; Matturro, Angela; Loglisci, Giuseppina; Latagliata, Roberto; Breccia, Massimo; Meloni, Giovanna; Alimena, Giuliana; Foà, Robin; Micozzi, Alessandra

    2012-01-01

    Background Posaconazole is effective as primary antifungal prophylaxis of invasive fungal diseases in patients with acute myeloid leukemia. Design and Methods The impact of primary antifungal prophylaxis administered during front-line chemotherapy for acute myeloid leukemia was evaluated by comparing 58 patients who received oral amphotericin B (control group) to 99 patients who received oral posaconazole (posaconazole group). The primary endpoint was the incidence of proven/probable invasive fungal diseases. Secondary endpoints included incidence of invasive aspergillosis, survival at 4 and 12 months after the diagnosis of acute myeloid leukemia and costs. Results Proven/probable invasive fungal diseases were documented in 51.7% of patients in the control group and in 23.2% in the posaconazole group (P=0.0002). Invasive aspergillosis was documented in 43% of patients in the control group and in 15% in the posaconazole group (P=0.002). No survival difference was observed in patients aged over 60 years. In patients aged 60 years or less, a statistically significant survival advantage was observed at 4 months, but no longer at 12 months, in the posaconazole group (P=0.03). It was calculated that in the posaconazole group there was a mean 50% cost reduction for the antifungal drugs. Conclusions Primary antifungal prophylaxis with posaconazole during front-line chemotherapy was effective in preventing invasive fungal diseases in a “real-life” scenario of patients with acute myeloid leukemia, resulted in an early but transitory survival advantage in younger patients and was economically advantageous. PMID:22102706

  1. Burden of fungal disease in Ireland.

    PubMed

    Dorgan, Eileen; Denning, David W; McMullan, Ronan

    2015-04-01

    Our objective was to estimate the burden of fungal disease on the island of Ireland, as part of a coordinated project estimating the global burden. Published epidemiology data describing fungal infection in Ireland were identified. Population and underlying disease data were collected for 2010 and a structured set of assumptions were applied to estimate burden of fungal disease based on immunosuppression, chronic disease, and other demographic information indicating predisposition to fungal infection. From Ireland's population of 6.4 million, we estimate 117, 000 patients develop significant fungal disease each year. By far the most common fungal disease is recurrent Candida vaginitis, with an estimated 95, 000 episodes annually (3000 per 100 000 women). Other fungal diseases which may be less well recognized are severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis, with estimated episodes per year of 11, 700 and 9000, respectively (182 and 140 per 100, 000 population, respectively). The model also estimates 450 episodes of invasive aspergillosis, 200 of chronic pulmonary aspergillosis, 600 of oesophageal candidiasis and 450 of candidaemia per year (7, 3, 9 and 6 episodes per 100, 000 population, respectively). This is, we believe, the first attempt to estimate the burden of fungal disease in our population and provides a basis for estimating its impact on human health and resource use. PMID:25596121

  2. Fungal glycan interactions with epithelial cells in allergic airway disease

    PubMed Central

    Roy, René M.; Klein, Bruce S.

    2014-01-01

    Human exposure to fungi results in a wide range of health outcomes, from invasive disease or allergy to immune tolerance. Inhaled fungi contact airway epithelial cells as an early event, and this host:fungal interaction can shape the eventual immunological outcome. Emerging evidence points to exposure to fungal cell wall carbohydrates in the development of allergic airway disease. Herein, we describe determinants of fungal allergenicity, and review the responses of airway epithelial cells to fungal carbohydrates. A greater understanding of the recognition of and response to fungal carbohydrates by airway epithelial cells may lead to the development of targeted therapies that ameliorate allergic airway disease. PMID:23602359

  3. Pre-hospital non-invasive ventilation for acute respiratory failure: a systematic review and cost-effectiveness evaluation.

    PubMed Central

    Pandor, Abdullah; Thokala, Praveen; Goodacre, Steve; Poku, Edith; Stevens, John W; Ren, Shijie; Cantrell, Anna; Perkins, Gavin D; Ward, Matt; Penn-Ashman, Jerry

    2015-01-01

    BACKGROUND Non-invasive ventilation (NIV), in the form of continuous positive airway pressure (CPAP) or bilevel inspiratory positive airway pressure (BiPAP), is used in hospital to treat patients with acute respiratory failure. Pre-hospital NIV may be more effective than in-hospital NIV but requires additional ambulance service resources. OBJECTIVES We aimed to determine the clinical effectiveness and cost-effectiveness of pre-hospital NIV compared with usual care for adults presenting to the emergency services with acute respiratory failure and to identify priorities for future research. DATA SOURCES Fourteen electronic databases and research registers (including MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature) were searched from inception to August 2013, supplemented by hand-searching reference lists and contacting experts in the field. REVIEW METHODS We included all randomised or quasi-randomised controlled trials of pre-hospital NIV in patients with acute respiratory failure. Methodological quality was assessed according to established criteria. An aggregate data network meta-analysis (NMA) of mortality and intubation was used to jointly estimate intervention effects relative to usual care. A NMA, using individual patient-level data (IPD) and aggregate data where IPD were not available, was carried out to assess whether or not covariates were treatment effect modifiers. A de novo economic model was developed to explore the costs and health outcomes when pre-hospital NIV (specifically CPAP provided by paramedics) and standard care (in-hospital NIV) were applied to a hypothetical cohort of patients with acute respiratory failure. RESULTS The literature searches identified 2284 citations. Of the 10 studies that met the inclusion criteria, eight were randomised controlled trials and two were quasi-randomised trials (six CPAP; four BiPAP; sample sizes 23-207 participants). IPD were

  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. PMID:26449508

  5. 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

  6. Cutaneous infection caused by Cylindrocarpon lichenicola in a patient with acute myelogenous leukemia.

    PubMed

    Iwen, P C; Tarantolo, S R; Sutton, D A; Rinaldi, M G; Hinrichs, S H

    2000-09-01

    Cylindrocarpon lichenicola is a saprophytic soil fungus which has rarely been associated with human disease. We report the first case of localized invasive cutaneous infection caused by this fungus in a 53-year-old male from the rural midwestern United States with relapsed acute myelogenous leukemia. On admission for induction chemotherapy, the patient was noted to have an abrasive laceration between the fourth and fifth metacarpophalangeal joints and on the dorsum of the right hand, which progressed to frank ulceration following chemotherapy. A biopsy provided an initial diagnosis of an invasive fungal infection consistent with aspergillosis based on the histopathological appearance of the mold in tissue. Multiple positive fungal cultures which were obtained from the biopsied tissue were subsequently identified by microscopic and macroscopic characteristics to be C. lichenicola. The infection resolved following marrow regeneration, aggressive debridement of the affected tissue, and treatment with amphotericin B. This case extends the conditions associated with invasive disease caused by C. lichenicola. PMID:10970386

  7. 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. PMID:27108701

  8. Influence of pre-existing invasive aspergillosis on allo-HSCT outcome: a retrospective EBMT analysis by the Infectious Diseases and Acute Leukemia Working Parties.

    PubMed

    Penack, O; Tridello, G; Hoek, J; Socié, G; Blaise, D; Passweg, J; Chevallier, P; Craddock, C; Milpied, N; Veelken, H; Maertens, J; Ljungman, P; Cornelissen, J; Thiebaut-Bertrand, A; Lioure, B; Michallet, M; Iacobelli, S; Nagler, A; Mohty, M; Cesaro, S

    2016-03-01

    Historically, invasive aspergillosis (IA) has been a major barrier for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The influence of invasive IA on long-term survival and on transplant-related complications has not been investigated in a larger patient cohort under current conditions. Our aim was to analyze the long-term outcome of patients undergoing allo-HSCT with a history of prior IA. We used European Society for Blood and Marrow Transplantation database data of first allo-HSCTs performed between 2005 and 2010 in patients with acute leukemia. One thousand one hundred and fifty patients with data on IA before allo-HSCT were included in the analysis. The median follow-up time was 52.1 months. We found no significant impact of IA on major transplant outcome variables such as overall survival, relapse-free survival, non-relapse mortality, cumulative incidence of acute GvHD grade II-IV, chronic GvHD, pulmonary complications and leukemia relapse. However, we found a trend toward lower overall survival (P=0.078, hazard ratio (HR) (95% confidence interval (CI)): 1.16 (0.98, 1.36)) and higher non-relapse mortality (P=0.150, HR (95% CI): 1.19 (0.94, 1.50)) in allo-HSCT recipients with pre-existing IA. Our data suggest that a history of IA should not generally be a contraindication when considering the performance of allo-HSCT in patients with acute leukemia. PMID:26501769

  9. Mucosal immunization with PsaA protein, using chitosan as a delivery system, increases protection against acute otitis media and invasive infection by Streptococcus pneumoniae.

    PubMed

    Xu, J-H; Dai, W-J; Chen, B; Fan, X-Y

    2015-03-01

    As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal immunity plays an important role in the prevention of pneumococcal diseases. Therefore, intranasal vaccination may be an effective immunization strategy, but requires appropriate mucosal vaccine delivery systems. In this work, chitosan was used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on ionotropic gelation methods and used to immunize BALB/c mice intranasally. Compared to mice immunized with naked PsaA, levels of IFN-γ, IL-17A and IL-4 in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced significantly in mice inoculated with chitosan-PsaA. Furthermore, increased protection against acute otitis media following middle ear challenge with pneumococcus serotype 14, and improved survival following intraperitoneal challenge with pneumococcus serotype 3 or serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles. Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal and systemic immune responses and increase protection against pneumococcal acute otitis media and invasive infections. Hence, intranasal immunization with PsaA protein, based on chitosan as a delivery system, is an efficient immunization strategy for preventing pneumococcal infections. PMID:25565478

  10. Adhesins in Human Fungal Pathogens: Glue with Plenty of Stick

    PubMed Central

    de Groot, Piet W. J.; Bader, Oliver; de Boer, Albert D.; Weig, Michael

    2013-01-01

    Understanding the pathogenesis of an infectious disease is critical for developing new methods to prevent infection and diagnose or cure disease. Adherence of microorganisms to host tissue is a prerequisite for tissue invasion and infection. Fungal cell wall adhesins involved in adherence to host tissue or abiotic medical devices are critical for colonization leading to invasion and damage of host tissue. Here, with a main focus on pathogenic Candida species, we summarize recent progress made in the field of adhesins in human fungal pathogens and underscore the importance of these proteins in establishment of fungal diseases. PMID:23397570

  11. Long-term non-invasive ventilation reduces readmissions in COPD patients with two or more episodes of acute hypercapnic respiratory failure

    PubMed Central

    Ankjærgaard, Kasper Linde; Maibom, Sophia Liff; Wilcke, Jon Torgny

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) patients who have had an episode of acute hypercapnic respiratory failure (AHRF) have a large 1-year risk of death or readmission. Acute non-invasive ventilation (NIV) has been shown to be an effective treatment of AHRF; and long-term NIV (LTNIV) has been shown to be an effective treatment of chronic respiratory failure in stable hypercapnic COPD. We investigated the effects of LTNIV in a group of patients with severe, unstable COPD: frequent admissions and multiple previous episodes of AHRF treated with NIV. Methods We conducted a retrospective analysis of 20 COPD patients treated with LTNIV after two or more episodes of AHRF during 1 year. Results The mean number of AHRF episodes decreased from 2.44 in the year prior to LTNIV initiation to 0.44 in the year following (p<0.0001). The median number of admissions decreased from 5.19 to 1.88 (p=0.0092). Four patients (20%) died in 1 year. LTNIV tended to reduce arterial CO2. No changes were found in lung function. Conclusions LTNIV seems effective in reducing recurrent AHRF and readmissions in a highly select group of patients with severe, unstable COPD and frequent AHRF. PMID:27036658

  12. 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

  13. 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

  14. Fungal Skin Infections

    MedlinePlus

    ... Fungal Skin Infections Overview of Fungal Skin Infections Candidiasis Overview of Dermatophytoses (Ringworm, Tinea) Athlete's Foot Jock ... are caused by yeasts (such as Candida —see Candidiasis ) or dermatophytes, such as Epidermophyton, Microsporum, and Trichophyton ( ...

  15. Noninvasive and invasive positive pressure ventilation for acute respiratory failure in critically ill patients: a comparative cohort study

    PubMed Central

    Meeder, Annelijn M.; Tjan, Dave H. T.

    2016-01-01

    Background Noninvasive positive pressure ventilation (NPPV) for acute respiratory failure in the intensive care unit (ICU) is associated with a marked reduction in intubation rate, complications, hospital length of stay and mortality. Multiple studies have indicated that patients failing NPPV have worse outcomes compared with patients with successful NPPV treatment; however limited data is available on risks associated with NPPV failure resulting in (delayed) intubation and outcomes compared with initial intubation. The purpose of this study is to assess rates and predictors of NPPV failure and to compare hospital outcomes of patients with NPPV failure with those patients primarily intubated without a prior NPPV trial. Methods A retrospective observational study using data from patients with acute respiratory failure admitted to the ICU in the period 2013–2014. All patients treated with NPPV were evaluated. A sample of patients who were primarily intubated was randomly selected to serve as controls for the group of patients who failed NPPV. Results NPPV failure was recorded in 30.8% of noninvasively ventilated patients and was associated with longer ICU stay [OR, 1.16, 95% confidence interval (95% CI): 1.04–1.30] and lower survival rates (OR, 0.10, 95% CI: 0.02–0.59) compared with NPPV success. Multivariate analysis showed presence of severe sepsis at study entry, higher Simplified Acute Physiology II Score (SAPS-II) score, lower ratio of arterial oxygen tension to fraction of inspired oxygen (PF-ratio) and lower plasma glucose were predictors for NPPV failure. After controlling for potential confounders, patients with NPPV failure did not show any difference in hospital outcomes compared with patients who were primarily intubated. Conclusions Patients with acute respiratory failure and NPPV failure have worse outcomes compared with NPPV success patients, however not worse than initially intubated patients. An initial trial of NPPV therefore may be suitable

  16. Entomopathogenic fungal endophytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal endophytes are quite common in nature and some of them have been shown to have adverse effects against insects, nematodes, and plant pathogens. An introduction to fungal endophytes will be presented, followed by a discussion of research aimed at introducing Beauveria bassiana as a fungal endo...

  17. 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. PMID:26937491

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

    ClinicalTrials.gov

    2016-04-08

    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

  19. When is an invasive palliative intervention in an acute internal medical patient worth it? A structured palliative approach.

    PubMed

    Weber, Thomas; Strasser, Florian

    2015-12-01

    A 67-year-old patient with coronary artery disease (CAD), diabetes, and chronic obstructive pulmonary disease (COPD) was scheduled for coronary artery bypass graft (CABG) surgery after a recent myocardial infarction despite a high perioperative risk of death. While waiting, acute renal failure developed, and the patient was admitted to the intensive care unit (ICU). After the patient and his wife were informed that CABG surgery was no longer possible, he declined further intensive care treatment and subsequently died peacefully.We show that a structured palliative approach which has been proposed for cancer patients may also be feasible in palliative situations concerning nononcologic patients. PMID:26620468

  20. 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.

  1. Effects of microcystin-LR on bacterial and fungal functional genes profile in rat gut.

    PubMed

    Lin, Juan; Chen, Jun; He, Jun; Chen, Jing; Yan, Qingyun; Zhou, Jizhong; Xie, Ping

    2015-03-01

    The short-term exposure to microcystin-LR (MC-LR, one of the most common and toxic variants generated by toxigenic cyanobacteria) induced gut dysfunction such as generation of reactive oxygen species, cell erosion and deficient intestinal absorption of nutrients. However, till now, little is known about its impact on gut microbial community, which has been considered as necessary metabolic assistant and stresses resistant entities for the host. This study was designed to reveal the shift of microbial functional genes in the gut of rat orally gavaged with MC-LR. GeoChip detected a high diversity of bacterial and fungal genes involved in basic metabolic processes and stress resistance. The results showed that the composition of functional genes was significantly changed in rat gut after one week of exposure to MC-LR, and we found some relatively enriched genes that are involved in carbon degradation including chitin, starch and limonene metabolism, and these genes were mainly derived from fungal and bacterial pathogens. In addition, we found large amounts of significantly enriched genes relevant to degradation of the specific carbon compounds, aromatics. The dysbiosis of bacterial and fungal flora gave an implication of pathogens invasion. The enriched gene functions could be linked to acute gastroenteritis induced by MC-LR. PMID:25617596

  2. Non-invasive cardiac index monitoring during cardiopulmonary functional testing provides additional prognostic value in patients after acute heart failure.

    PubMed

    Lee, Ming-Feng; Chen, Wei-Siang; Fu, Tieh-Cheng; Liu, Min-Hui; Wang, Jong-Shyan; Hsu, Chih-Chin; Huang, Yu-Yen; Cherng, Wen-Jin; Wang, Chao-Hung

    2012-01-01

    The prognostic value of parameters derived from a cardiopulmonary exercise test (CPET) is well established in patients stabilized after acute heart failure (HF). Under multidisciplinary disease management, this study sought to test whether noninvasive cardiac output (CO) monitoring (NICOM) during the CPET provides additional prognostic value. In total, 131 patients stabilized after acute HF agreed to undergo the CPET with NICOM. Outcome follow-up focused on composite events of death and HF-related rehospitalization. Patients with a peak cardiac index (CI) of ≤ 4.5 L/minute/ m(2) (n = 32), compared to those with a peak CI of > 4.5 L/minute/m(2) (n = 99), had higher incidences of diabetes mellitus (DM) and hypertension, but had lower hemoglobin levels, estimated glomerular filtration rates (eGFR), oxygen uptake efficiency slope (OUES), and peak oxygen uptake (VO(2)). During the 1.2 ± 0.7 years of follow-up, there were 8 (6.1%) deaths, and 16 (12.2%) HF-related rehospitalizations. In a Cox univariable analysis, a lower event-free survival was associated with a history of DM, a higher Ve/VCO(2) slope, lower peak VCO(2) and eGFR, and a peak CI of ≤ 4.5 L/minute/ m(2) (P < 0.05). The Cox multivariable analysis showed that the Ve/VCO(2) slope (hazard ratio (HR) = 1.08, 95% confidence interval (CI): 1.01~1.16, P = 0.02) and peak CI of ≤ 4.5 L/minute/m(2 )(HR = 3.26, 95% CI: 1.18~9.01, P = 0.02) were significant independent predictors. In conclusion, NICOM during the CPET was demonstrated to provide prognostic information in addition to traditional risk factors, biomarkers, and other well-established CPET parameters. PMID:23258137

  3. Non-invasive collection of exhaled breath condensate in rats: evaluation of pH, H₂O₂ and NOx in lipopolysaccharide-induced acute lung injury.

    PubMed

    de Broucker, Virginie; Hassoun, Sidi Mohamed; Hulo, Sébastien; Chérot-Kornobis, Nathalie; Nevière, Rémi; Matran, Régis; Sobaszek, Annie; Edme, Jean-Louis

    2012-11-01

    The analysis of exhaled breath condensate (EBC) offers the potential for identifying lung disease markers in humans and animals, but methodological issues and standardised procedures need to be addressed before the technique can be considered for use in applications to help understand the role of environmental pollution in respiratory diseases. The purpose of this study was to develop and implement a new device using a glass-chamber for collecting EBC non-invasively from rats in order to analyse EBC markers in lipopolysaccharide (LPS)-induced acute lung injury. Eighty-four adult rats were used in five different series of experiments to determine the source of EBC formation, intra-day and inter-day variability, and the influence of environmental parameters on EBC markers. The hypothesis that inflammation induces an oxidative stress was assessed by measuring pH, nitrogen oxides (NOx) and hydrogen peroxide (H(2)O(2)) in EBC. The results confirmed that EBC fluid was generated at the level of the respiratory tract. The repeatability studies of disease markers indicated higher concentrations of NOx and H(2)O(2) at midday compared to the morning, but there were no significant difference between measurements on consecutive days. EBC volume was influenced by both ambient temperature and humidity. Moreover, 3h after LPS challenge, significantly increased concentrations of both NOx and H(2)O(2) were observed in EBC of the LPS group compared with controls (P=0.005 and P=0.027, respectively). These results suggested that EBC collection may be a valuable tool to monitor the presence of markers, such as NOx and H(2)O(2), in an animal model of LPS-induced acute lung injury. PMID:22658821

  4. Current and future therapies for invasive aspergillosis.

    PubMed

    Bassetti, Matteo; Pecori, Davide; Della Siega, Paola; Corcione, Silvia; De Rosa, Francesco Giuseppe

    2015-06-01

    Invasive fungal infections have increase worldwide and represent a threat for immunocompromised patients including HIV-infected, recipients of solid organ and stem cell transplants, and patients receiving immunosuppressive therapies. High mortality rates and difficulties in early diagnosis characterize pulmonary fungal infections. Invasive pulmonary aspergillosis has been reviewed focussing on therapeutic management. Although new compounds have become available in the past years (i.e., amphotericin B lipid formulations, last-generation azoles, and echinocandines), new diagnostic tools and careful therapeutic management are mandatory to assure an early appropriate targeted treatment that represents the key factor for a successful conservative approach in respiratory fungal infections. PMID:24994691

  5. Prediction of Renal Allograft Acute Rejection Using a Novel Non-Invasive Model Based on Acoustic Radiation Force Impulse.

    PubMed

    Yang, Cheng; Jin, Yunjie; Wu, Shengdi; Li, Long; Hu, Mushuang; Xu, Ming; Rong, Ruiming; Zhu, Tongyu; He, Wanyuan

    2016-09-01

    Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post-transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation. PMID:27267289

  6. Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study

    PubMed Central

    Diener, Hans-Christoph; Silver, Nicholas; Magis, Delphine; Reuter, Uwe; Andersson, Annelie; Liebler, Eric J; Straube, Andreas

    2015-01-01

    Background Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH. Methods PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n = 48) with standard of care (SoC) alone (control (n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed. Results During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n = 45) had a significantly greater reduction in the number of attacks per week vs controls (n = 48) (−5.9 vs −2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p < 0.001). No serious treatment-related adverse events occurred. Conclusion Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC. PMID:26391457

  7. A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention

    PubMed Central

    Yuan, Min-Jie; Pan, Ye-Sheng; Hu, Wei-Guo; Lu, Zhi-Gang; Zhang, Qing-Yong; Huang, Dong; Huang, Xiao-Li; Wei, Meng; Li, Jing-Bo

    2015-01-01

    The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness. PMID:26885226

  8. Non-invasive Diagnosis of Acute Cellular Rejection in Liver Transplant Recipients: A Proteomic Signature Validated by ELISA

    PubMed Central

    Massoud, Omar; Heimbach, Julie; Viker, Kimberly; Krishnan, Anuradha; Poterucha, John; Sanchez, William; Watt, Kymberly; Wiesner, Russell; Charlton, Michael

    2011-01-01

    Diagnosis of acute cellular rejection (ACR) requires a liver biopsy with attendant expense, and risk. The first aim was to prospectively determine, in an exploratory analysis, whether there is a serum proteome signature associated with histologically confirmed ACR. The second aim was to use simpler and faster ELISA-based assays for proteins identified as differentially abundant in the proteomic analysis to identify patients with ACR in a separate validation cohort. We used sequential high abundance protein depletion and iTRAQ LC/MS/MS mass spectrometry to characterize the serum proteome in serum samples of patients with ACR and without ACR. Of the 41 proteins identified as differentially abundant, 7 (serum amyloid A (SAA), complement 4 (C4), fibrinogen, complement 1q (C1q), complement 3 (C3), Heat Shock Protein 60 (HSP60), and Heat Shock Protein 70 (HSP70)) could be measured using ELISA-based assays in a validation cohort of patients with ACR (n=25) and without ACR (n=21). Mean ALT levels in patients with and without ACR were (mean +/− SD) 198+/−27 and 153+/−34 U/L respectively. Among the seven proteins for which ELISA assays were available, C4 and C1q were both independent predictors for ACR. C4 had the greatest predictivity in differentiating patients with/without ACR. C4 of ≤0.31gm/L had a 97% sensitivity, 62% specificity, 74% positive predictive value and 94% negative predictive value. The combination C4 ≤0.31 gm/L and ALT ≥70 IU/ml had 96% sensitivity, 81% specificity, 86% positive predictive value and 94% negative predictive value. In summary, in this exploratory analysis, serum complement C4 and ALT levels are highly predictive of ACR in liver transplant recipients. Confirmation in a prospective, larger, diverse population is needed. PMID:21618694

  9. 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. PMID:26449500

  10. 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

    2016-06-01

    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. PMID:27237365

  11. 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

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

    2016-05-01

    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

  12. Fungal and Bacterial Diseases.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal and bacterial diseases are important constraints to production. Recognition of diseases and information on their biology is important in disease management. This chapter is aimed at providing diagnostic information on fungal and bacterial diseases of sugar beet and their biology, epidemiolo...

  13. 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

  14. 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. PMID:24945887

  15. Fungal infections in renal transplant patients.

    PubMed

    Khan, Asif; El-Charabaty, Elie; El-Sayegh, Suzanne

    2015-06-01

    Organ transplantation has always been considered to be the standard therapeutic interventions in patients with end-stage organ failure. In 2008, more than 29,000 organ transplants were performed in US. Survival rates among transplant recipients have greatly improved due to better understanding of transplant biology and more effective immunosuppressive agents. After transplant, the extent of the immune response is influenced by the amount of interleukin 2 (IL-2) being produced by the T-helper cells. Transplant immunosuppressive therapy primarily targets T cell-mediated graft rejection. Calcineurin inhibitor, which includes cyclosporine, pimecrolimus and tacrolimus, impairs calcineurin-induced up-regulation of IL-2 expression, resulting in increased susceptibility to invasive fungal diseases. This immunosuppressive state allows infectious complication, leading to a high mortality rate. Currently, overall mortality due to invasive fungal infections (IFIs) in solid organ transplant recipients ranges between 25% and 80%. The risk of IFI following renal transplant is associated with the dosage of immunosuppressive agents given, environmental factors and post-transplant duration. Most fungal infections occur in the first 6 months after transplant because of the use of numerous immunosuppressors. Candida spp. and Cryptococcus spp. are the yeasts most frequently isolated, while most frequent filamentous fungi (molds) isolated are Aspergillus spp. The symptoms of systemic fungal infections are non-specific and early detection of fungal infections and proper therapy are important in improving survival and reducing mortality. This article will provide an insight on the risk factors and clinical presentation, compare variation in treatment of IFIs in renal transplant patients, and evaluate the role of prophylactic therapy in this group of patients. We also report the course and management of two renal transplant recipients admitted to Staten Island University Hospital, both of

  16. Fungal Infections in Renal Transplant Patients

    PubMed Central

    Khan, Asif; El-Charabaty, Elie; El-Sayegh, Suzanne

    2015-01-01

    Organ transplantation has always been considered to be the standard therapeutic interventions in patients with end-stage organ failure. In 2008, more than 29,000 organ transplants were performed in US. Survival rates among transplant recipients have greatly improved due to better understanding of transplant biology and more effective immunosuppressive agents. After transplant, the extent of the immune response is influenced by the amount of interleukin 2 (IL-2) being produced by the T-helper cells. Transplant immunosuppressive therapy primarily targets T cell-mediated graft rejection. Calcineurin inhibitor, which includes cyclosporine, pimecrolimus and tacrolimus, impairs calcineurin-induced up-regulation of IL-2 expression, resulting in increased susceptibility to invasive fungal diseases. This immunosuppressive state allows infectious complication, leading to a high mortality rate. Currently, overall mortality due to invasive fungal infections (IFIs) in solid organ transplant recipients ranges between 25% and 80%. The risk of IFI following renal transplant is associated with the dosage of immunosuppressive agents given, environmental factors and post-transplant duration. Most fungal infections occur in the first 6 months after transplant because of the use of numerous immunosuppressors. Candida spp. and Cryptococcus spp. are the yeasts most frequently isolated, while most frequent filamentous fungi (molds) isolated are Aspergillus spp. The symptoms of systemic fungal infections are non-specific and early detection of fungal infections and proper therapy are important in improving survival and reducing mortality. This article will provide an insight on the risk factors and clinical presentation, compare variation in treatment of IFIs in renal transplant patients, and evaluate the role of prophylactic therapy in this group of patients. We also report the course and management of two renal transplant recipients admitted to Staten Island University Hospital, both of

  17. 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. PMID:23698366

  18. 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.

  19. The Use of Crop Proteomics and Fungal Genomics in Elucidating Fungus-Crop Interactions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the complex interrelationships of plant and fungal gene products during the host plant-Aspergillus flavus interaction is key in developing strategies to interrupt the aflatoxin contamination process. Fungal processes necessary for invasion of the plant and production of aflatoxin can ...

  20. 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

  1. 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. PMID:25963605

  2. Insect pathology and fungal entomopathogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungi that occur inside asymptomatic plant tissues are known as fungal endophytes. Different genera of fungal entomopathogens have been reported as naturally occurring fungal endophytes, and it has been shown that it is possible to inoculate plants with fungal entomopathogens, making them endophytic...

  3. Nail Fungal Infections

    MedlinePlus

    ... medicines can treat a fungal nail infection. Oral antifungal medicines help a new nail grow to replace ... infected nail. You might need to take the antifungal medicine for 6 to 12 weeks. It depends ...

  4. 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

  5. Fungal Nail Infection (Onychomycosis)

    MedlinePlus

    ... vinegar, vitamin E oil, Vicks® VapoRub®, or tea tree oil. When to Seek Medical Care Fungal nail ... Trusted Links Related diseases: Psoriasis View all diseases Community: Discussion Forum Skinmatters Blog About Us | Terms of ...

  6. Fungal Eye Infections

    MedlinePlus

    ... Zoonotic Infectious Disease Division of Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Fungal Eye Infections Recommend on ... Zoonotic Infectious Disease Division of Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch File Formats Help: How do ...

  7. 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

  8. 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. PMID:22167394

  9. Fungal Diagnostics in Pneumonia

    PubMed Central

    Lease, Erika D.; Alexander, Barbara D.

    2014-01-01

    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. While standard techniques such as microscopy and culture remain the mainstay of diagnosis, relatively recent advances in serologic and molecular testing are important additions to the field. This chapter will review the laboratory tools used to diagnose fungal respiratory disease. PMID:22167394

  10. Indoor fungal exposure.

    PubMed

    Rogers, Christine A

    2003-08-01

    Fungi affect humans in complex ways and are capable of eliciting a number of disease responses, such as infectious, allergic, and irritant and toxic effects. Fungal exposure is unequivocally associated with exacerbations of asthma, although the role of fungi in causing the disease is yet to be determined. The association between home dampness and respiratory health effects is strong, and fungal exposure is suspected to be associated with this linkage. Fear of toxin exposures has generated debate over the possible toxic health effects of airborne fungi; however, several recent reviews discount the health impacts of mycotoxin through indoor exposures. Nevertheless, fungal contamination of indoor environments is undesirable. Knowledge of sources and characteristics of fungal spore release and dispersal are important for understanding the processes of exposure. Environmental monitoring for fungi and their disease agents are important aspects of exposure assessment, but few guidelines exist for interpreting their health impacts. Much work is needed in isolating, characterizing and standardizing fungal disease agents to properly assess the prevalence of fungal health effects. PMID:14524388

  11. 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

  12. Invasive intracranial pressure monitoring is a useful adjunct in the management of severe hepatic encephalopathy associated with pediatric acute liver failure

    PubMed Central

    Kamat, Pradip; Kunde, Sachin; Vos, Miriam; Vats, Atul; Heffron, Thomas; Romero, Rene; Fortenberry, James D.

    2011-01-01

    Introduction Pediatric acute liver failure (ALF) is often accompanied by hepatic encephalopathy, cerebral edema and raised intracranial pressure (ICP). Elevated ICP can be managed more effectively with intracranial monitoring, but ALF-associated coagulopathy is often considered a contraindication for invasive monitoring due to risk for intracranial bleeding. We reviewed our experience with use of early ICP monitoring in ALF in children listed for liver transplantation. Methods Retrospective review of all intubated pediatric ALF patients with Grade 3 and Grade 4 encephalopathy requiring intracranial pressure monitoring and evaluated for potential liver transplant were identified from an institutional liver transplant patient database from 1999 to 2009. Result 14 patients were identified that met inclusion criteria. Age ranged from 7 months to 20 yrs. Diagnoses of ALF were infectious (3), drug induced (7), autoimmune hepatitis (2) and indeterminate (2). Grade 3 and 4 encephalopathy was seen in 10 (71%) and 4 (29%) patients respectively. CT scans prior to ICP monitor placement showed cerebral edema in 5 (35.7%) patients. Prior to ICP monitor placement, fresh frozen plasma, Vitamin K and activated recombinant factor VIIa were given to all 14 patients with significant improvement in coagulopathy (p<.04). Initial ICP ranged from 5 – 50 cmH2O; ICP was significantly higher in patients with cerebral edema by CT (p<.05). 11/14 (78%) patients received hypertonic saline and 3 (22%) received mannitol for elevated ICP. 8 of 14 (56%) monitored patients were managed to liver transplant with 100% surviving neurologically intact. 4/14 (28%) patients had spontaneous recovery without liver transplant. 2 of 14 (14%) patients died due to multiple organ failure prior to transplant. One patient had a small 9mm intracranial hemorrhage but survived after receiving a liver transplant. No patient developed intracranial infection. Conclusion In our series of patients, ICP monitoring had a

  13. Sphingolipids as targets for treatment of fungal infections.

    PubMed

    Rollin-Pinheiro, Rodrigo; Singh, Ashutosh; Barreto-Bergter, Eliana; Del Poeta, Maurizio

    2016-08-01

    Invasive fungal infections have significantly increased in the last few decades. Three classes of drugs are commonly used to treat these infections: polyenes, azoles and echinocandins. Unfortunately each of these drugs has drawbacks; polyenes are toxic, resistance against azoles is emerging and echinocandins have narrow spectrum of activity. Thus, the development of new antifungals is urgently needed. In this context, fungal sphingolipids have emerged as a potential target for new antifungals, because their biosynthesis in fungi is structurally different than in mammals. Besides, some fungal sphingolipids play an important role in the regulation of virulence in a variety of fungi. This review aims to highlight the diverse strategies that could be used to block the synthesis or/and function of fungal sphingolipids. PMID:27502288

  14. 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…

  15. [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. PMID:27395023

  16. Allergic Fungal Rhinosinusitis.

    PubMed

    Hoyt, Alice E W; Borish, Larry; Gurrola, José; Payne, Spencer

    2016-01-01

    This article reviews the history of allergic fungal rhinosinusitis and the clinical, pathologic, and radiographic criteria necessary to establish its diagnosis and differentiate this disease from other types of chronic rhinosinusitis. Allergic fungal rhinosinusitis is a noninvasive fungal form of sinus inflammation characterized by an often times unilateral, expansile process in which the typical allergic "peanut-butter-like" mucin contributes to the formation of nasal polyps, hyposmia/anosmia, and structural changes of the face. IgE sensitization to fungi is a necessary, but not sufficient, pathophysiologic component of the disease process that is also defined by microscopic visualization of mucin-containing fungus and characteristic radiological imaging. This article expounds on these details and others including the key clinical and scientific distinctions of this diagnosis, the pathophysiologic mechanisms beyond IgE-mediated hypersensitivity that must be at play, and areas of current and future research. PMID:27393774

  17. Fungal synthesis of exopolysaccharides

    SciTech Connect

    Griffith, W.L.; Compere, A.L.

    1984-01-01

    Several fungal polysaccharides are currently used as thickening agents for materials ranging from enhanced oil recovery brines and drilling muds to foods. These polymers are generally produced during exponential fungal growth and appear to be normal cell wall constituents. As thickeners, they tend to be comparable to xanthan, and exhibit a similar non-Newtonian response to shear. Polymers which do not have carboxyl or amine group substituents tend to be less sensitive to high concentrations of multivalent ions, a problem in many brine and food systems. The fungal polymers have related fermentations and separations. They compete for a similar product market. Where families of polymers have a common backdone, they are susceptible to hydrolysis by the same enzymes.

  18. 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

  19. 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. PMID:26691607

  20. Rapidly advancing invasive endomyocardial aspergillosis.

    PubMed

    Davutoglu, Vedat; Soydinc, Serdar; Aydin, Abdullah; Karakok, Metin

    2005-02-01

    The exposure to Aspergillus organisms/spores is likely common, but disease caused by tissue invasion with these fungi is uncommon and occurs primarily in the setting of immunosuppression. We report a case of rapidly advancing invasive endomyocardial aspergillosis secondary to prolonged usage of multiple broad-spectrum antibiotics in a nonimmunocompromised host. A 36-year-old cotton textile worker presented to our institution with a 3-month history of weight loss and fatigue. He reported receiving prolonged use of multiple broad-spectrum antibiotic treatment. The echocardiogram demonstrated multiple endomyocardial vegetations and a mass in the left atrium. Myocardial biopsy specimen revealed an invasive endomyocardial aspergillosis. The patient was investigated for immune deficiency including HIV, and this workup was negative. Treatment was started with amphotericin B and heparin for presumed left atrial thrombus. The patient died because of a rupture of mycotic aneurysm that resulted in cerebral hemorrhage. This case illustrates the risk of an invasive fungal infection in a nonimmunocompromised host who is a prolonged user of antibiotics in the setting of environmental exposure of opportunistic invasive fungal infections. PMID:15682058

  1. 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

  2. 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 ...

  3. 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

  4. A combination approach to treating fungal infections.

    PubMed

    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

  5. 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. PMID:25943906

  6. Hypoxia and Fungal Pathogenesis: To Air or Not To Air?

    PubMed Central

    Grahl, Nora; Shepardson, Kelly M.; Chung, Dawoon

    2012-01-01

    Over the last 3 decades, the frequency of life-threatening human fungal infections has increased as advances in medical therapies, solid-organ and hematopoietic stem cell transplantations, an increasing geriatric population, and HIV infections have resulted in significant rises in susceptible patient populations. Although significant advances have been made in understanding how fungi cause disease, the dynamic microenvironments encountered by fungi during infection and the mechanisms by which they adapt to these microenvironments are not fully understood. As inhibiting and preventing in vivo fungal growth are main goals of antifungal therapies, understanding in vivo fungal metabolism in these host microenvironments is critical for the improvement of existing therapies or the design of new approaches. In this minireview, we focus on the emerging appreciation that pathogenic fungi like Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus are exposed to oxygen-limited or hypoxic microenvironments during fungal pathogenesis. The implications of these in vivo hypoxic microenvironments for fungal metabolism and pathogenesis are discussed with an aim toward understanding the potential impact of hypoxia on invasive fungal infection outcomes. PMID:22447924

  7. 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 ...

  8. The White-Nose Syndrome Transcriptome: Activation of Anti-fungal Host Responses in Wing Tissue of Hibernating Little Brown Myotis.

    PubMed

    Field, Kenneth A; Johnson, Joseph S; Lilley, Thomas M; Reeder, Sophia M; Rogers, Elizabeth J; Behr, Melissa J; Reeder, DeeAnn M

    2015-10-01

    White-nose syndrome (WNS) in North American bats is caused by an invasive cutaneous infection by the psychrophilic fungus Pseudogymnoascus destructans (Pd). We compared transcriptome-wide changes in gene expression using RNA-Seq on wing skin tissue from hibernating little brown myotis (Myotis lucifugus) with WNS to bats without Pd exposure. We found that WNS caused significant changes in gene expression in hibernating bats including pathways involved in inflammation, wound healing, and metabolism. Local acute inflammatory responses were initiated by fungal invasion. Gene expression was increased for inflammatory cytokines, including interleukins (IL) IL-1β, IL-6, IL-17C, IL-20, IL-23A, IL-24, and G-CSF and chemokines, such as Ccl2 and Ccl20. This pattern of gene expression changes demonstrates that WNS is accompanied by an innate anti-fungal host response similar to that caused by cutaneous Candida albicans infections. However, despite the apparent production of appropriate chemokines, immune cells such as neutrophils and T cells do not appear to be recruited. We observed upregulation of acute inflammatory genes, including prostaglandin G/H synthase 2 (cyclooxygenase-2), that generate eicosanoids and other nociception mediators. We also observed differences in Pd gene expression that suggest host-pathogen interactions that might determine WNS progression. We identified several classes of potential virulence factors that are expressed in Pd during WNS, including secreted proteases that may mediate tissue invasion. These results demonstrate that hibernation does not prevent a local inflammatory response to Pd infection but that recruitment of leukocytes to the site of infection does not occur. The putative virulence factors may provide novel targets for treatment or prevention of WNS. These observations support a dual role for inflammation during WNS; inflammatory responses provide protection but excessive inflammation may contribute to mortality, either by

  9. The White-Nose Syndrome Transcriptome: Activation of Anti-fungal Host Responses in Wing Tissue of Hibernating Little Brown Myotis

    PubMed Central

    Field, Kenneth A.; Johnson, Joseph S.; Lilley, Thomas M.; Reeder, Sophia M.; Rogers, Elizabeth J.; Behr, Melissa J.; Reeder, DeeAnn M.

    2015-01-01

    White-nose syndrome (WNS) in North American bats is caused by an invasive cutaneous infection by the psychrophilic fungus Pseudogymnoascus destructans (Pd). We compared transcriptome-wide changes in gene expression using RNA-Seq on wing skin tissue from hibernating little brown myotis (Myotis lucifugus) with WNS to bats without Pd exposure. We found that WNS caused significant changes in gene expression in hibernating bats including pathways involved in inflammation, wound healing, and metabolism. Local acute inflammatory responses were initiated by fungal invasion. Gene expression was increased for inflammatory cytokines, including interleukins (IL) IL-1β, IL-6, IL-17C, IL-20, IL-23A, IL-24, and G-CSF and chemokines, such as Ccl2 and Ccl20. This pattern of gene expression changes demonstrates that WNS is accompanied by an innate anti-fungal host response similar to that caused by cutaneous Candida albicans infections. However, despite the apparent production of appropriate chemokines, immune cells such as neutrophils and T cells do not appear to be recruited. We observed upregulation of acute inflammatory genes, including prostaglandin G/H synthase 2 (cyclooxygenase-2), that generate eicosanoids and other nociception mediators. We also observed differences in Pd gene expression that suggest host-pathogen interactions that might determine WNS progression. We identified several classes of potential virulence factors that are expressed in Pd during WNS, including secreted proteases that may mediate tissue invasion. These results demonstrate that hibernation does not prevent a local inflammatory response to Pd infection but that recruitment of leukocytes to the site of infection does not occur. The putative virulence factors may provide novel targets for treatment or prevention of WNS. These observations support a dual role for inflammation during WNS; inflammatory responses provide protection but excessive inflammation may contribute to mortality, either by

  10. 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

  11. Invasive mucormycosis in chronic granulomatous disease.

    PubMed

    Al-Otaibi, Abdulnasir M; Al-Shahrani, Dayel A; Al-Idrissi, Eman M; Al-Abdely, Hail M

    2016-05-01

    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

  12. 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

  13. 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. PMID:23428378

  14. Invasive aspergillosis in primary immunodeficiencies.

    PubMed

    Almyroudis, N G; Holland, S M; Segal, B H

    2005-05-01

    Primary immunodeficiencies are rare and usually first manifest during childhood. Invasive aspergillosis is the leading cause of mortality in chronic granulomatous disease (CGD), reflecting the key role of the phagocyte NADPH oxidase in host defense against opportunistic fungi. Despite interferon-gamma prophylaxis, invasive filamentous fungal infections are a persistent problem in CGD. Key principles of management of fungal infections involve early recognition and aggressive treatment and appropriate surgical debridement of localized disease. Because CGD is a disorder of phagocyte stem cells in which the gene defects are well defined, it is a model disease to evaluate immune reconstitution through stem cell transplantation and gene therapy. Patients with the hyper-IgE syndrome with recurrent infections (Job syndrome) are prone to colonization of lung cavities (pneumatoceles) by Aspergillus species leading to local invasion and rarely disseminated infection. Other primary phagocytic disorders, T-cell disorders, and mitochondrial disorders are uncommonly associated with invasive aspergillosis. Taken together, these rare primary immunodeficiencies highlight the complex coordination of both innate and acquired pathways mediating host defense against Aspergillus infection. PMID:16110817

  15. 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

  16. Fungal toenail infections

    PubMed Central

    2014-01-01

    Introduction Fungal infections are reported to cause 23% of foot diseases and 50% of nail conditions in people seen by dermatologists, but are less common in the general population, affecting 3% to 12% of people. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral treatments for fungal toenail infections in adults? What are the effects of topical treatments for fungal toenail infections in adults? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 13 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amorolfine, butenafine, ciclopirox, fluconazole, itraconazole, terbinafine, tioconazole, and topical ketoconazole. PMID:24625577

  17. Fungal toenail infections

    PubMed Central

    2011-01-01

    Introduction Fungal infections are reported to cause 23% of foot diseases and 50% of nail conditions in people seen by dermatologists, but are less common in the general population, affecting 3% to 5% of people. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral treatments for fungal toenail infections? What are the effects of topical treatments for fungal toenail infections? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: amorolfine, butenafine, ciclopirox, fluconazole, griseofulvin, itraconazole, ketoconazole, mechanical debridement, terbinafine, and tioconazole. PMID:21846413

  18. Fungal toenail infections

    PubMed Central

    2008-01-01

    Introduction Fungal infections are reported to cause 23% of foot diseases and 50% of nail conditions in people seen by dermatologists, but are less common in the general population, affecting 3-5% of people. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral treatments for fungal toenail infections? What are the effects of topical treatments for fungal toenail infections? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 11 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: amorolfine, butenafine, ciclopirox, fluconazole, griseofulvin, itraconazole, ketoconazole, mechanical debridement, terbinafine, and tioconazole. PMID:19445781

  19. 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. PMID:25749258

  20. 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. PMID:26449504

  1. 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. PMID:18312538

  2. 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

  3. Invasive aspergillosis complicating Cushing's syndrome.

    PubMed

    Walsh, T J; Mendelsohn, G

    1981-08-01

    Patients with Cushing's syndrome are susceptible to opportunistic infections. Invasive fungal infections in patients with Cushing's syndrome caused by endogenous glucocorticoid excess rarely are reported, and aspergillosis occurring in this setting, to our knowledge, has not been described. Two patients with Cushing's syndrome and notably elevated levels of circulating cortisol had invasive aspergillosis develop. A patient with endogenous hypercortisolism caused by adrenal cortical carcinoma suffered a subarachnoid hemorrhage from rupture of an Aspergillus mycotic aneurysm. The other patient, who had an adrenocorticotrophic hormone-producing prostatic carcinoma, had pulmonary and disseminated aspergillosis develop. Exogenous corticosteroids are known clinically and experimentally to facilitate disseminated aspergillosis. Endogenous hypercortisolism also may bae an important factor predisposing to invasive aspergillosis. PMID:7259386

  4. 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. PMID:12901327

  5. 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. PMID:22006283

  6. [Fungal colonization in preterm neonates weighing less than 1500g admitted to the neonatal intensive care unit].

    PubMed

    Benjamin, M D; Jolivet, E; Desbois, N; Pignol, J; Ketterer-Martinon, S; Pierre-Louis, L; Flechelles, O

    2016-09-01

    Fungal colonization is a common occurrence in preterm neonates. Our objective was to describe the profile and characteristics of fungal colonization in preterm infants admitted to the Martinique NICU. From March 2012 to January 2013, an epidemiological prospective cohort study was conducted with 57 very low-birth-weight infants. Cutaneous, rectal, gastric, respiratory, and urinary swabs were collected on admission, then every week for 4 weeks. The prevalence of fungal colonization was 68% (39/57): 46% by Malassezia species, 28% by Candida parapsilosis, 19% by C. albicans, 5% by C. glabrata, and 2% by C. guilliermondii. The colonized patients had a duration of parenteral nutrition and antibiotic therapy longer than the others (P<0.05). Nosocomial colonization (after 2 days of life) occurred in 52% of cases: Malassezia species and C. parapsilosis were the commensal skin yeasts most frequently implicated. Forty-nine percent (28/57) had suspected invasive fungal infections that received probabilistic treatment. Only one case of invasive fungal infection with C. glabrata was diagnosed. This study highlights the important role played by nosocomial transmission in the colonization of preterm newborns. Mycological surveillance cultures in the NICU are very useful for monitoring fungal ecology and can improve the prevention of fungal colonization in preterm infants at risk of invasive fungal infection. PMID:27364939

  7. Three Cases of Fungal Disease with Neuro-Ophthalmic Manifestations Associated with Post-Hurricane Environment

    PubMed Central

    Sridhar, Jayanth; Lam, Byron L.; Pasol, Joshua; Sternau, Linda

    2011-01-01

    Allergic fungal sinusitis (AFS) is thought to represent an immunologic response to exposure to dematiaceous fungi. These fungi are known to cause disease more frequently in hot, humid climates and seasons. Three patients presented with unusual manifestations of fungal disease after exposure to environments recently affected by hurricanes. Two patients had AFS, one with gradual painless visual loss from an AFS mass extending into the suprasellar region and one with orbital apex syndrome. Another patient had invasive fungal disease and developed orbital apex syndrome. The cases underscore the importance of clinical recognition of fungal disease in patients with sinus, orbital, or skull base involvement as well as its potential for causing permanent visual loss. This report suggests a potential association between fungal disease and tropical storm exposure. PMID:21799448

  8. CD4+ T cell STAT3 phosphorylation precedes acute GVHD, and subsequent Th17 tissue invasion correlates with GVHD severity and therapeutic response

    PubMed Central

    Betts, Brian C.; Sagatys, Elizabeth M.; Veerapathran, Anandharaman; Lloyd, Mark C.; Beato, Francisca; Lawrence, Harshani R.; Yue, Binglin; Kim, Jongphil; Sebti, Said M.; Anasetti, Claudio; Pidala, Joseph

    2015-01-01

    Th17 cells contribute to severe GVHD in murine bone marrow transplantation. Targeted deletion of the RORγt transcription factor or blockade of the JAK2-STAT3 axis suppresses IL-17 production and alloreactivity by Th17 cells. Here, we show that pSTAT3 Y705 is increased significantly in CD4+ T cells among human recipients of allogeneic HCT before the onset of Grade II–IV acute GVHD. Examination of target-organ tissues at the time of GVHD diagnosis indicates that the amount of RORγt + Th17 cells is significantly higher in severe GVHD. Greater accumulation of tissue-resident Th17 cells also correlates with the use of MTX- compared with Rapa-based GVHD prophylaxis, as well as a poor therapeutic response to glucocorticoids. RORγt is optimally suppressed by concurrent neutralization of TORC1 with Rapa and inhibition of STAT3 activation with S3I-201, supporting that mTOR- and STAT3-dependent pathways converge upon RORγt gene expression. Rapa-resistant T cell proliferation can be totally inhibited by STAT3 blockade during initial allosensitization. We conclude that STAT3 signaling and resultant Th17 tissue accumulation are closely associated with acute GVHD onset, severity, and treatment outcome. Future studies are needed to validate the association of STAT3 activity in acute GVHD. Novel GVHD prevention strategies that incorporate dual STAT3 and mTOR inhibition merit investigation. PMID:25663681

  9. Fungal Susceptibility of Polyurethanes

    PubMed Central

    Darby, Richard T.; Kaplan, Arthur M.

    1968-01-01

    One hundred laboratory-synthesized polyurethanes were tested by a mixed-culture petri dish method for susceptibility to fungus attack. Polyether polyurethanes were moderately to highly resistant to fungal attack, whereas all polyester polyurethanes tested were highly susceptible. The susceptibility of the polyethers was related to the number of adjacent methylene groups in the polymer chain. At least two such groups were required for appreciable attack to occur. The presence of side chains on the diol moiety of the polyurethane reduced susceptibility. Images Fig. 1 Fig. 2 Fig. 3 PMID:16349806

  10. Approach to the Solid Organ Transplant Patient with Suspected Fungal Infection.

    PubMed

    Anesi, Judith A; Baddley, John W

    2016-03-01

    In solid organ transplant (SOT) recipients, invasive fungal infections (IFIs) are associated with significant morbidity and mortality. Detection of IFIs can be difficult because the signs and symptoms are similar to those of viral or bacterial infections, and diagnostic techniques have limited sensitivity and specificity. Clinicians must rely on knowledge of the patient's risk factors for fungal infection to make a diagnosis. The authors describe their approach to the SOT recipient with suspected fungal infection. The epidemiology of IFIs in the SOT population is reviewed, and a syndromic approach to suspected IFI in SOT recipients is described. PMID:26739603

  11. Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease.

    PubMed

    Matsumura-Kimoto, Yayoi; Inamoto, Yoshihiro; Tajima, Kinuko; Kawajiri, Akihisa; Tanaka, Takashi; Hirakawa, Tsuneaki; Ino, Kazuko; Asao, Yu; Tamogami, Hiroyuki; Kono, Chika; Takeda, Wataru; Okinaka, Keiji; Fuji, Shigeo; Kurosawa, Saiko; Kim, Sung-Won; Tanosaki, Ryuji; Yamashita, Takuya; Fukuda, Takahiro

    2016-06-01

    This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses ≥ 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses ≥ 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses. PMID:26968790

  12. 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. PMID:26810078

  13. Fungal Entomopathogens in the Rhizosphere

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Entomopathogenic fungi are found in a wide variety of fungal groups from water molds to basidiomycetes, yet there are a number of fungal groups with no entomopathogenic representative. The order Hypocreales contains the largest number of entomogenous fungi including two of the most widely studied, ...

  14. 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. PMID:27101887

  15. Natural Sources as Innovative Solutions Against Fungal Biofilms.

    PubMed

    Girardot, Marion; Imbert, Christine

    2016-01-01

    Fungal cells are capable of adhering to biotic and abiotic surfaces and form biofilms containing one or more microbial species that are microbial reservoirs. These biofilms may cause chronic and acute infections. Fungal biofilms related to medical devices are particularly responsible for serious infections such as candidemia. Nowadays, only a few therapeutic agents have demonstrated activities against fungal biofilms in vitro and/or in vivo. So the discovery of new anti-biofilm molecules is definitely needed. In this context, biodiversity is a large source of original active compounds including some that have already proven effective in therapies such as antimicrobial compounds (antibacterial or antifungal agents). Bioactive metabolites from natural sources, useful for developing new anti-biofilm drugs, are of interest. In this chapter, the role of molecules isolated from plants, lichens, algae, microorganisms, or from animal or human origin in inhibition and/or dispersion of fungal biofilms (especially Candida and Aspergillus biofilms) is discussed. Some essential oils, phenolic compounds, saponins, peptides and proteins and alkaloids could be of particular interest in fighting fungal biofilms. PMID:27115410

  16. 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

  17. 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. PMID:26449505

  18. [Impact of acute respiratory failure on survival of COPD patients managed with long-term non-invasive ventilation and oxygen therapy].

    PubMed

    Perrin, C; Vandenbos, F; Tamisier, R; Lemoigne, F; Blaive, B

    2000-02-01

    Our study aimed to assess the impact of acute respiratory failure (ARF) on survival of patients with chronic obstructive pulmonary disease (COPD) receiving long-term oxygen therapy (LTOT) plus nasal intermittent positive pressure ventilation (NIPPV). Survival was analysed retrospectively in 24 patients with severe COPD initiated to NIPPV in addition to LTOT. Fourteen patients were established on NIPPV following exacerbation of acute respiratory failure which has required mechanical ventilation (group 1). Ten patients (group 2) have never been hospitalized for ARF. Comparison of clinical details at baseline, 6 months, 1, 2, and 3 years for the two groups failed to reveal any difference with the exception of prior episodes of ARF. The probability of survival at 3 years was 65% (95% confidence interval [CI] 43-86) for the overall population, 46% (95% CI 15-77) in group 1, and 74% (95% CI 42-105) in group 2. The difference between the two groups was statistically significant. We show that ARF requiring mechanical ventilation appears to be a factor that is negatively correlated with survival for patients treated by LTOT plus NIPPV. This data suggests that NIPPV should be tried before ARF arising in COPD patients who present a deterioration in chronic respiratory failure with hypercapnia. PMID:10756560

  19. The Acute Transcriptomic and Proteomic Response of HC-04 Hepatoma Cells to Hepatocyte Growth Factor and its Implications for Plasmodium falciparum Sporozoite Invasion*

    PubMed Central

    Tao, Dingyin; King, Jonas G.; Tweedell, Rebecca E.; Jost, Philipp J.; Boddey, Justin A.; Dinglasan, Rhoel R.

    2014-01-01

    The routine study of human malaria liver-stage biology in vitro is hampered by low infection efficiency of human hepatocellular carcinoma (HCC) lines (<0.1%), poor understanding of steady-state HCC biology, and lack of appropriate tools for trace sample analysis. HC-04 is the only HCC that supports complete development of human malaria parasites. We hypothesized that HCCs are in various intermediate stages of the epithelial-mesenchymal transition (EMT) and HC-04s retain epithelial characteristics that permit infection. We developed a facile analytical approach to test this hypothesis viz. the HC-04 response to hepatocyte growth factor (HGF). We used online two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS) to quantify protein expression profiles in HC-04 pre-/post-HGF treatment and validated these results by RT-qPCR and microscopy. We successfully increased protein identification efficiency over offline-2D methods by 12-fold, using less sample material, allowing robust protein quantification. We observed expected up-regulation and down-regulation of EMT protein markers in response to HGF, but also unexpected cellular responses. We also observed that HC-04 is generally more susceptible to HGF-mediated signaling than what was observed for HepG2, a widely used, but poor malaria liver stage-HCC model. Our analytical approach to understanding the basic biology of HC-04 helps us understand the factors that may influence its utility as a model for malaria liver-stage development. We observed that HC-04 treatment with HGF prior to the addition of Plasmodium falciparum sporozoites did not facilitate cell invasion, which suggests unlinking the effect of HGF on malaria liver stage development from hepatocyte invasion. Finally, our 2D-LC-MS/MS approach and broadly applicable experimental strategy should prove useful in the analysis of various hepatocyte-pathogen interactions, tumor progression, and early disease events. PMID:24532842

  20. 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

  1. Potential involvement of Aspergillus flavus laccases in peanut invasion at low water potential

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aspergillus flavus (Link) accumulates aflatoxins in peanuts, mainly affecting immature kernels during drought. Peanut invasion by A. flavus induces synthesis of phytoalexins, mostly stilbenoids, as a plant defense mechanism. Fungal laccases are often related to pathogenicity, and among other subst...

  2. Locally invasive pulmonary aspergillosis occurring in a gardener: an occupational hazard?

    PubMed Central

    Zuk, J A; King, D; Zakhour, H D; Delaney, J C

    1989-01-01

    Fatal locally invasive pulmonary aspergillosis occurred in a previously fit young patient who had no predisposing factors other than exposure to fungal spores in his occupation as a gardener. Images PMID:2678581

  3. 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. PMID:27086365

  4. Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice.

    PubMed

    Wu, Xilin; Liu, Li; Cheung, Ka-Wai; Wang, Hui; Lu, Xiaofan; Cheung, Allen Ka Loon; Liu, Wan; Huang, Xiuyan; Li, Yanlei; Chen, Zhiwei W; Chen, Samantha M Y; Zhang, Tong; Wu, Hao; Chen, Zhiwei

    2016-09-01

    Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV-1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and P24(+) cells in peripheral blood and various tissue compartments, we found that systemic infections were rapidly established in NSG-HuPBL mice by both HIV-1 strains. Although comparable peripheral viral loads were detected during acute infection, the T/F virus appeared to cause less CD4(+) T cell loss and less numbers of infected cells in different organs and tissue compartments. Both viruses, however, invaded brains with P24(+)/CD3(+) T cells detected primarily in meninges, cerebral cortex and perivascular areas. Critically, brain infections with HIV-1JR-FL but not with HIV-1BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1(+) microglial cells and GFAP(+) astrocytes, respectively. The increased Iba1(+) microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN(+) neurons in brains of infected animals. Our findings, therefore, indicate the establishment of two useful NSG-HuPBL models, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis. PMID:26838362

  5. Epidemiology of Invasive Fungal Infections in the Mediterranean Area

    PubMed Central

    Binder, Ulrike; Lass-Flörl, Cornelia

    2011-01-01

    Although Candida species remain the relevant cause of IFI, other fungi (especially moulds) have become increasingly prevalent. In particular, Aspergillus species are the leading cause of mould infections but also Glomeromycota (formerly Zygomycetes) and Fusarium species are increasing in frequency, and are associated with high mortality rates. Many of these emerging infections occur as breakthrough infections in patients treated with new antifungal drugs. The causative pathogens, incidence rate and severity are dependent on the underlying condition, as well as on the geographic location of the patient population. France and Italy show the highest incident rates of Fusarium infections in Europe, following the US, where numbers are still increasing. Scedosporium prolificans, which primarily is found in soil in Spain and Australia, is most frequently isolated from blood cultures in a Spanish hospital. Geotrichum capitatum represents another species predominantly found in Europe with especially high rates in Mediterranean countries. The increasing resistance to antifungal drugs especially of these new emerging pathogens is a severe problem for managing these IFIs. PMID:21625305

  6. 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. PMID:26972663

  7. 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

  8. Adoptive T-cell therapy for fungal infections in haematology patients

    PubMed Central

    Deo, Shivashni S; Gottlieb, David J

    2015-01-01

    The prolonged immune deficiency resulting from haematopoietic stem cell transplant and chemotherapy predisposes to a high risk of invasive fungal infections. Despite the recent advances in molecular diagnostic testing, early initiation of pre-emptive antifungal therapy and the use of combination pharmacotherapy, mortality from invasive mould infections remain high among recipients of allogeneic stem cell transplant. The increasing incidences of previously rare and drug-resistant strains of fungi present a further clinical challenge. Therefore, there is a need for novel strategies to combat fungal infections in the immunocompromised. Adoptive therapy using in vitro-expanded fungus-specific CD4 cells of the Th-1 type has shown clinical efficacy in murine studies and in a small human clinical study. Several techniques for the isolation and expansion of fungus-specific T cells have been successfully applied. Here we discuss the incidence and changing patterns of invasive fungal diseases, clinical evidence supporting the role of T cells in fungal immunity, methods to expand fungus-specific T cells in the laboratory and considerations surrounding the use of T cells for fungal immunotherapy. PMID:26366286

  9. 5T4 oncofetal antigen is expressed in high risk of relapse childhood pre-B acute lymphoblastic leukemia and is associated with a more invasive and chemotactic phenotype.

    PubMed

    Castro, F V; McGinn, O J; Krishnan, S; Marinov, G; Li, J; Rutkowski, A J; Elkord, E; Burt, D J; Holland, M; Vaghjiani, R; Gallego, A; Saha, V; Stern, P L

    2012-07-01

    Although the overall prognosis in childhood acute lymphoblastic leukemia (ALL) is good, outcome after relapse is poor. Recurrence is frequently characterized by the occurrence of disease at extramedullary sites, such as the central nervous system and testes. Subpopulations of blasts able to migrate to such areas may have a survival advantage and give rise to disease recurrence. Gene expression profiling of 85 diagnostic pre-B-ALL bone marrow samples revealed higher 5T4 oncofetal antigen transcript levels in cytogenetic high-risk subgroups of patients (P<0.001). Flow cytometric analysis determined that bone marrow from relapse patients have a significantly higher percentage of 5T4-positive leukemic blasts than healthy donors (P=0.005). The high-risk Sup-B15 pre-B-ALL line showed heterogeneity in 5T4 expression, and the derived, 5T4(+) (Sup5T4) and 5T4(-) (Sup) subline cells, displayed differential spread to the omentum and ovaries following intraperitoneal inoculation of immunocompromised mice. Consistent with this, Sup5T4 compared with Sup cells show increased invasion in vitro concordant with increased LFA-1 and VLA-4 integrin expression, adhesion to extracellular matrix and secretion of matrix metalloproteases (MMP-2/-9). We also show that 5T4-positive Sup-B15 cells are susceptible to 5T4-specific superantigen antibody-dependent cellular toxicity providing support for targeted immunotherapy in high-risk pre-B-ALL. PMID:22266911

  10. Cancer Patients and Fungal Infections

    MedlinePlus

    ... mould-related diseases in immunocompromised patients. Journal of Antimicrobial Chemotherapy 2011;66:i5-i14. Ribaud P. Fungal ... al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update ...

  11. Fungal Biotransformation of Tetracycline Antibiotics.

    PubMed

    Shang, Zhuo; Salim, Angela A; Khalil, Zeinab; Bernhardt, Paul V; Capon, Robert J

    2016-08-01

    The commercial antibiotics tetracycline (3), minocycline (4), chlortetracycline (5), oxytetracycline (6), and doxycycline (7) were biotransformed by a marine-derived fungus Paecilomyces sp. to yield seco-cyclines A-H (9-14, 18 and 19) and hemi-cyclines A-E (20-24). Structures were assigned by detailed spectroscopic analysis, and in the case of 10 X-ray crystallography. Parallel mechanisms account for substrate-product specificity, where 3-5 yield seco-cyclines and 6 and 7 yield hemi-cyclines. The susceptibility of 3-7 to fungal biotransformation is indicative of an unexpected potential for tetracycline "degradation" (i.e., antibiotic resistance) in fungal genomes. Significantly, the fungal-derived tetracycline-like viridicatumtoxins are resistant to fungal biotransformation, providing chemical insights that could inform the development of new tetracycline antibiotics resistant to enzymatic degradation. PMID:27419475

  12. Biosynthesis of Fungal Indole Alkaloids

    PubMed Central

    Xu, Wei; Gavia, Diego J.; Tang, Yi

    2014-01-01

    This review provides a summary of recent research advances in elucidating the biosynthesis of fungal indole alkaloids. Different strategies used to incorporate and derivatize the indole/indoline moieties in various families of fungal indole alkaloids will be discussed, including tryptophan-containing nonribosomal peptides and polyketide-nonribosomal peptide hybrids; and alkaloids derived from other indole building blocks. This review also includes discussion regarding the downstream modifications that generate chemical and structural diversity among indole alkaloids. PMID:25180619

  13. 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

  14. Neurospora illuminates fungal photoreception.

    PubMed

    Chen, Chen-Hui; Dunlap, Jay C; Loros, Jennifer J

    2010-11-01

    Light not only is indispensable as an energy source for life on earth but also serves as an essential environmental cue conveying the information of daily and seasonal time to organisms across different kingdoms. Although the molecular mechanisms underlying light responses are actively explored in various light-sensitive organisms, these studies are either hindered by the complexity of the systems or an incomplete familiarity with the light signaling components involved in the scheme. Therefore, study of a simple and well-characterized model system is desirable to expand our knowledge of basic properties underlying the regulation of biological light responses. This review will briefly introduce the basic light sensing machinery in Neurospora crassa, a filamentous fungus, and then focus on the most recent advances in employing Neurospora as a model to study light signaling cascades, photoadaptation, and circadian clock-modulated effects in eukaryotic cells. Also, we will summarize the functions of a number of putative photoreceptors in Neurospora, and discuss the implications of the study of Neurospora to the field of fungal photobiology and some challenges for future studies. PMID:20637887

  15. Comparison of Noninvasively and Invasively Managed Patients, With or Without Revascularization in Non-ST Elevation Myocardial Infarction (from the Acute Coronary Syndrome Israeli Survey).

    PubMed

    Blatt, Alex; Kalmanovich, Eran; Karny-Rahkovich, Orit; Brener, Svetlana; Shlezinger, Meital; Shlomo, Nir; Vered, Zvi; Hod, Hanoch; Goldenberg, Ilan; Elbaz-Greener, Gabby

    2016-07-01

    Patients with non-ST elevation myocardial infarction who are managed noninvasively at presentation or are catheterized but without revascularization represent a heterogeneous and understudied population. We evaluated the clinical characteristics, management strategies, and outcomes of patients with non-ST elevation myocardial infarction (NSTEMI) who were enrolled in the prospective biannual Acute Coronary Syndrome Israeli Surveys from 2004 to 2013. Patients were divided into 3 groups: no catheterization (no angio), catheterization with revascularization (angio-revascularized), and catheterization without revascularization (angio-nonrevascularized) groups. The study included 3,198 patients with NSTEMI. Coronary angiography was performed in 2,525 (79%) during the index hospitalization, of whom 1899 (59%) underwent revascularization. Evidence-based therapies were administered during the index hospitalization at a significantly higher rate to those in the angio-revascularized group compared with the other 2 groups. Multivariate analysis showed that compared with those in the angio-revascularized and angio-nonrevascularized groups, patients in the no angio group experienced a significantly higher risk for 1-year mortality (hazard ratio 2.04 [p ≤0.0001] and 1.21 [p = 0.01], respectively). The risk associated with no revascularized was consistent in each risk subset analyzed, including an older age, and increased creatinine levels. In conclusion, our data, from a large real-world contemporary experience, suggest that patients with NSTEMI who do not undergo coronary revascularization during the index hospitalization represent a greater risk and undertreated group with increased risk for long-term mortality. PMID:27217207

  16. Invasive mammals.

    PubMed

    Moutou, F; Pastoret, P P

    2010-08-01

    Every region of the world is concerned by potential mammal invasions, as humans are already present on all the world's land masses. All these invasions are a result of species introductions by humans for one reason or another. The authors briefly review the known movements and observed consequences of mammal-related invasions. They take examples from all five continents, as well as from a few island systems. The ancient introduction of game species, and later of domestic species, has been followed more recently by movements of commercial species. We are now seeing the emergence of what are known as entertainment species. In a number of cases, such introductions have led to the establishment of new epidemiological cycles that previously might never have been thought possible. According to current indicators, this phenomenon is not on the wane. PMID:20919577

  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. PMID:25660409

  18. 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

  19. Fungal prosthetic valve endocarditis with mycotic aneurysm: Case report.

    PubMed

    Brandão, Mariana; Almeida, Jorge; Ferraz, Rita; Santos, Lurdes; Pinho, Paulo; Casanova, Jorge

    2016-09-01

    Fungal prosthetic valve endocarditis is an extremely severe form of infective endocarditis, with poor prognosis and high mortality despite treatment. Candida albicans is the most common etiological agent for this rare but increasingly frequent condition. We present a case of fungal prosthetic valve endocarditis due to C. albicans following aortic and pulmonary valve replacement in a 38-year-old woman with a history of surgically corrected tetralogy of Fallot, prior infective endocarditis and acute renal failure with need for catheter-based hemodialysis. Antifungal therapy with liposomal amphotericin B was initiated prior to cardiac surgery, in which the bioprostheses were replaced by homografts, providing greater resistance to recurrent infection. During hospitalization, a mycotic aneurysm was diagnosed following an episode of acute arterial ischemia, requiring two vascular surgical interventions. Despite the complications, the patient's outcome was good and she was discharged on suppressive antifungal therapy with oral fluconazole for at least a year. The reported case illustrates multiple risk factors for fungal endocarditis, as well as complications and predictors of poor prognosis, demonstrating its complexity. PMID:27493128

  20. 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

  1. Fungal sensing of host environment.

    PubMed

    Braunsdorf, C; Mailänder-Sánchez, D; Schaller, M

    2016-09-01

    To survive inside a host, fungi have to adapt to a changing and often hostile environment and therefore need the ability to recognize what is going on around them. To adapt to different host niches, they need to sense external conditions such as temperature, pH and to recognize specific host factors. The ability to respond to physiological changes inside the host, independent of being in a commensal, pathogenic or even symbiotic context, implicates mechanisms for sensing of specific host factors. Because the cell wall is constantly in contact with the surrounding, fungi express receptors on the surface of their cell wall, such as pheromone receptors, which have important roles, besides mediating chemotropism for mating. We are not restricting the discussion to the human host because the receptors and mechanisms used by different fungal species to sense their environment are often similar even for plant pathogens. Furthermore, the natural habitat of opportunistic pathogenic fungi with the potential to cause infection in a human host is in soil and on plants. While the hosts' mechanisms of sensing fungal pathogens have been addressed in the literature, the focus of this review is to fill the gap, giving an overview on fungal sensing of a host-(ile) environment. Expanding our knowledge on host-fungal interactions is extremely important to prevent and treat diseases of pathogenic fungi, which are important issues in human health and agriculture but also to understand the delicate balance of fungal symbionts in our ecosystem. PMID:27155351

  2. 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

  3. Fatal-Stroke Syndrome Revealing Fungal Cerebral Vasculitis Due to Arthrographis kalrae in an Immunocompetent Patient ▿

    PubMed Central

    Pichon, N.; Ajzenberg, D.; Desnos-Ollivier, M.; Clavel, M.; Gantier, J. C.; Labrousse, F.

    2008-01-01

    We report an uncommon clinical presentation of a unique case of fatal invasive fungal cerebral vasculitis due to Arthrographis kalrae in a nonimmunocompromised host. The identity of the fungus was determined by morphological characteristics and by analysis of internal transcribed spacer 1 sequences and was confirmed by postmortem examination of the brain tissues. Establishing rapidly the link between the clinical syndromes and the fungal infection of the central nervous system is essential to improve the outcome. As our case has shown, it is more challenging to make a diagnosis of fungal infection when there are no risk factors of immunodeficiency and when the clinical presentation seems uncommon. PMID:18650350

  4. 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

    2016-01-01

    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. PMID:27230564

  5. Compatability of a Biological Control Agent with Herbicides for Control of Invasive Plant Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kudzu, Pueraria montana var lobata, is an exotic invasive weed that is difficult to control with available products and management practices. The fungal pathogen, Myrothecium verrucaria, is being developed as a bioherbicide for kudzu and other invasive vines. This biological control agent might be...

  6. 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. PMID:27418297

  7. Directed Evolution of Fungal Laccases

    PubMed Central

    Maté, Diana; García-Ruiz, Eva; Camarero, Susana; Alcalde, Miguel

    2011-01-01

    Fungal laccases are generalists biocatalysts with potential applications that range from bioremediation to novel green processes. Fuelled by molecular oxygen, these enzymes can act on dozens of molecules of different chemical nature, and with the help of redox mediators, their spectrum of oxidizable substrates is further pushed towards xenobiotic compounds (pesticides, industrial dyes, PAHs), biopolymers (lignin, starch, cellulose) and other complex molecules. In recent years, extraordinary efforts have been made to engineer fungal laccases by directed evolution and semi-rational approaches to improve their functional expression or stability. All these studies have taken advantage of Saccharomyces cerevisiae as a heterologous host, not only to secrete the enzyme but also, to emulate the introduction of genetic diversity through in vivo DNA recombination. Here, we discuss all these endeavours to convert fungal laccases into valuable biomolecular platforms on which new functions can be tailored by directed evolution. PMID:21966249

  8. The diversity of fungal genome.

    PubMed

    Mohanta, Tapan Kumar; Bae, Hanhong

    2015-01-01

    The genome size of an organism varies from species to species. The C-value paradox enigma is a very complex puzzle with regards to vast diversity in genome sizes in eukaryotes. Here we reported the detailed genomic information of 172 fungal species among different fungal genomes and found that fungal genomes are very diverse in nature. In fungi, the diversity of genomes varies from 8.97 Mb to 177.57 Mb. The average genome sizes of Ascomycota and Basidiomycota fungi are 36.91 and 46.48 Mb respectively. But higher genome size is observed in Oomycota (74.85 Mb) species, a lineage of fungus-like eukaryotic microorganisms. The average coding genes of Oomycota species are almost doubled than that of Acomycota and Basidiomycota fungus. PMID:25866485

  9. 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. PMID:25031775

  10. 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 ...

  11. Fungal biotransformation of furanocoumarins by Aspergillus niger

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungi metabolize polycyclic aromatic hydrocarbons by a number of detoxification processes. Prevalent fungal detoxification pathways for aromatic compounds include the formation of sulfate and glycosidated conjugates. Such fungal metabolism has been extensively studied as models of mammalian metabo...

  12. Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive aspergillosis.

    PubMed

    Paulussen, Caroline; Boulet, Gaëlle; Bosschaerts, Tom; Cos, Paul; Fortin, Anny; Maes, Louis

    2015-03-01

    Invasive aspergillosis (IA) has become increasingly common and is characterised by high morbidity and mortality. Upcoming resistance threatens treatment with azoles and highlights the continuous need for novel therapeutics. This laboratory study investigated the in vitro and in vivo potential of the alkylphospholipid oleylphosphocholine (OlPC) against Aspergillus. In vitro activities of OlPC, miltefosine, posaconazole and voriconazole were determined for Aspergillus fumigatus, A. niger, A. terreus and A. flavus. In vivo efficacy of OlPC was evaluated in a systemic A. fumigatus mouse model, adopting a short-term and long-term oral or intraperitoneal dosing regimen. OlPC showed good in vitro activity against A. fumigatus (IC50 = 1.04 μmol l(-1)). Intraperitoneal administration of 50 mg kg(-1) day(-1) OlPC significantly reduced the fungal organ burdens at 4 days post-infection (dpi). Although 5- and 10-day OlPC treatment improved survival, organ burdens were not affected at 10 and 15 dpi. While this study showed excellent in vitro activity of OlPC against Aspergillus spp., its therapeutic efficacy in an acute mouse model for IA was less convincing. Given the limited therapeutic options in the current antifungal market for invasive infections, OlPC activity should be assessed in a less stringent in vivo model, potentially in combination treatment with other already marketed antifungal drugs. PMID:25590577

  13. 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...

  14. 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 ...

  15. Subseafloor basalts as fungal habitats

    NASA Astrophysics Data System (ADS)

    Ivarsson, M.

    2012-02-01

    The oceanic crust is believed to host the largest potential habitat for microbial life on Earth, yet, next to nothing is known about this deep, concealed biosphere. 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:s 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, and probably still is. It is suggested that near future ocean drilling programs prioritize sampling of live species to better understand this concealed biosphere.

  16. 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.

  17. 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

  18. Interactions of fungal pathogens with phagocytes.

    PubMed

    Erwig, Lars P; Gow, Neil A R

    2016-03-01

    The surveillance and elimination of fungal pathogens rely heavily on the sentinel behaviour of phagocytic cells of the innate immune system, especially macrophages and neutrophils. The efficiency by which these cells recognize, uptake and kill fungal pathogens depends on the size, shape and composition of the fungal cells and the success or failure of various fungal mechanisms of immune evasion. In this Review, we describe how fungi, particularly Candida albicans, interact with phagocytic cells and discuss the many factors that contribute to fungal immune evasion and prevent host elimination of these pathogenic microorganisms. PMID:26853116

  19. Positive Feedback between Mycorrhizal Fungi and Plants Influences Plant Invasion Success and Resistance to Invasion

    PubMed Central

    Zhang, Qian; Yang, Ruyi; Tang, Jianjun; Yang, Haishui; Hu, Shuijin; Chen, Xin

    2010-01-01

    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. PMID:20808770

  20. Fungal communities as an experimental approach to Darwin's naturalization hypothesis.

    PubMed

    Morales, María Camila; Verdejo, Valentina; Orlando, Julieta; Carú, Margarita

    2016-01-01

    Darwin's naturalization hypothesis suggests that the success of an invasive species will be lower when colonizing communities are formed by phylogenetically related rather than unrelated species due to increased competition. Although microbial invasions are involved in both natural and anthropogenic processes, factors affecting the success of microbial invaders are unknown. A biological invasion assay was designed using Trichoderma cf. harzianum as the invader and two types of recipient communities assembled in microcosm assays: communities phylogenetically related to the invader, and communities phylogenetically unrelated to it. Both types of communities were invaded by T. cf. harzianum, and the success of colonization was monitored by qPCR; its effect on the genetic structure of recipient fungal communities was then assessed by DGGE profiles. T. cf. harzianum established itself in both communities, reaching 1000-10,000 times higher copy numbers in the non-related communities. However, invader establishment does not affect the structure of the invaded communities. These results suggest that the composition of recipient communities and their phylogenetic relationship to the invader affect the success of colonization by T. cf. harzianum. While this approach represents a very simplified assay, these microcosms enable an experimental test of Darwin's hypothesis in order to understand the biological invasion process in microbial communities. PMID:26506029

  1. Fungal Infections and New Biologic Therapies.

    PubMed

    Vallabhaneni, Snigdha; Chiller, Tom M

    2016-05-01

    The development of biologic therapies targeting proinflammatory mediators has led to significant advances in the treatment of immune-mediated inflammatory diseases (IMIDs). Blocking undesired inflammatory effects also has the potential to disrupt the body's immune response and increase the risk for infections, including fungal infections. This review summarizes the published data on the frequency and risk for fungal infections among patients treated with biologics, with a focus on the newer therapies approved for use with IMIDs in the last 10 years. The use of biologics is associated with a small but important risk of fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and candidiasis are some of the most common fungal infections associated with biologics. Providers should be vigilant for fungal infection among patients taking biologics, be aware that biologic agents may alter the typical presentation of fungal infections, and take timely steps to diagnose and treat fungal infection to reduce resultant morbidity and mortality. PMID:27032792

  2. 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

  3. 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. PMID:26365383

  4. Panfungal PCR Assay for Detection of Fungal Infection in Human Blood Specimens

    PubMed Central

    Van Burik, Jo-Anne; Myerson, David; Schreckhise, Randall W.; Bowden, Raleigh A.

    1998-01-01

    A novel panfungal PCR assay which detects the small-subunit rRNA gene sequence of the two major fungal organism groups was used to test whole-blood specimens obtained from a series of blood or bone marrow transplant recipients. The 580-bp PCR product was identified after amplification by panfungal primers and hybridization to a 245-bp digoxigenin-labeled probe. The lower limit of detection of the assay was approximately four organisms per milliliter of blood. Multiple whole-blood specimens from five patients without fungal infection or colonization had negative PCR results. Specimens from 11 infected patients had positive PCR results. Blood from three patients with pulmonary aspergillosis had positive PCR results: one patient’s blood specimen obtained in the week prior to the diagnosis of infection by a positive bronchoalveolar lavage fluid culture result was positive by PCR, and blood specimens obtained from two patients 1 to 2 days after lung biopsy and which were sterile by culture were positive by PCR. The blood of four patients with candidemia, three patients with mixed fungal infections, and one patient with fusariosis also had positive PCR signals. The panfungal PCR assay can detect multiple fungal genera and may be used as an adjunct to conventional methods for the detection of fungal infection or for describing the natural history of fungal infection. Further studies are needed to define the sensitivity and specificity of this assay for the diagnosis of fungal infection prior to the existence of other clinical or laboratory indications of invasive fungal infection. PMID:9574670

  5. 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

  6. 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

  7. Endoscopic cystogastrostomy: minimally invasive approach for pancreatic pseudocyst.

    PubMed

    Sial, Gull-Zareen Khan; Qazi, Abid Quddus; Yusuf, Mohammed Aasim

    2015-01-01

    Pancreatic pseudocysts in children are not uncommon. Non-resolving pseudocysts often require surgical intervention. Endoscopic cystogastrostomy is a minimally invasive procedure which is recommended for this condition. We report a large pancreatic pseudocyst in a 4-year old child, which developed following therapy with PEG-Asparaginase for acute lymphoblastic leukemia. It was managed with minimally invasive procedure. PMID:25628993

  8. Endoscopic Cystogastrostomy: Minimally Invasive Approach for Pancreatic Pseudocyst

    PubMed Central

    Sial, Gull-Zareen Khan; Yusuf, Mohammed Aasim

    2015-01-01

    Pancreatic pseudocysts in children are not uncommon. Non-resolving pseudocysts often require surgical intervention. Endoscopic cystogastrostomy is a minimally invasive procedure which is recommended for this condition. We report a large pancreatic pseudocyst in a 4-year old child, which developed following therapy with PEG-Asparaginase for acute lymphoblastic leukemia. It was managed with minimally invasive procedure. PMID:25628993

  9. 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.

  10. [Non invasive ventilation in the emergency setting].

    PubMed

    Wilhelm, Laetitia; Della Santa, Vincent; Hanhart, Walter-Alexandre

    2015-08-12

    Before the development of non invasive ventilation (NIV), endotracheal intubation was the only ventilatory therapy available in case of severe respiratory distress and acute respiratory failure. NIV used to be employed in intensive care settings only. Nowadays, the use of NIV has been democratized to include the emergency room, and the pre-hospital care setting for treatment of acute respiratory failure. Cardiogenic pulmonary edema and acute exacerbation of COPD are indications of choice, since NIV improves mortality. The efficiency of the therapy depends on early treatment; however, endotracheal intubation should not be delayed when it becomes necessary. PMID:26449102

  11. 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. PMID:22737589

  12. 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

  13. [Invasive yeast infections in severely burned patients].

    PubMed

    Renau, Ana Isabel; García-Vidal, Carolina; Salavert, Miguel

    2016-01-01

    Currently, there are few studies on candidaemia in the severely burned patient. These patients share the same risk factors for invasive fungal infections as other critically ill patients, but have certain characteristics that make them particularly susceptible. These include the loss of skin barrier due to extensive burns, fungal colonisation of the latter, and the use of hydrotherapy or other topical therapies (occasionally with antimicrobials). In addition, the increased survival rate achieved in recent decades in critically burned patients due to the advances in treatment has led to the increase of invasive Candida infections. This explains the growing interest in making an earlier and more accurate diagnosis, as well as more effective treatments to reduce morbidity and mortality of candidaemia in severe burned patients. A review is presented on all aspects of the burned patient, including the predisposition and risk factors for invasive candidiasis, pathogenesis of candidaemia, underlying immunodeficiency, local epidemiology and antifungal susceptibility, evolution and prognostic factors, as well as other non-Candida yeast infections. Finally, we include specific data on our local experience in the management of candidaemia in severe burned patients, which may serve to quantify the problem, place it in context, and offer a realistic perspective. PMID:27395025

  14. Establishment of invasive and non-invasive reporter systems to investigate American elm-Ophiostoma novo-ulmi interactions.

    PubMed

    Sherif, S; Jones, A M P; Shukla, M R; Saxena, P K

    2014-10-01

    Dutch elm disease (DED), caused by ascomycete fungi in the Ophiostoma genus, is the most devastating disease of American elm (Ulmus americana) trees. Cerato ulmin (CU), a hydrophobin secreted by the fungus, has been implicated in the development of DED, but its role in fungal pathogenicity and virulence remains uncertain and controversial. Here, we describe reporter systems based on the CU promoter and three reporter proteins (GFP, GUS and LUC), developed as research tools for quantitative and qualitative studies of DED in vitro, in vivo and in planta. A strain of the aggressive species Ophiostoma novo-ulmi was transformed with the reporter constructs using Agrobacterium-mediated transformation and the fungal transformants, namely M75-GFP, M75-GUS and M75-LUC, were examined for mitotic stability after repeated subcultures. The intensity of GFP fluorescence was strong in M75-GFP spores and hyphae, allowing microscopic investigations of spore structure, fungal morphogenesis and fungal development. The interaction of M75-GFP and U. americana callus cells was explored with scanning laser confocal microscopy facilitating qualitative studies on fungal strategies for the invasion and penetration of elm cells. M75-GUS was generated to provide an invasive, yet quantitative approach to study fungal-plant interactions in vitro and in planta. The generation of M75-LUC transformants was aimed at providing a non-destructive quantitative approach to study the role of CU in vivo. The sensitivity, low background signal and linearity of LUC assays all predict a very reliable approach to investigate and re-test previously claimed roles of this CU in fungal pathogenicity. These reporter systems provide new tools to investigate plant-pathogen interactions in this complex pathosystem and may aid in better understanding the development of DED. PMID:25139300

  15. 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 ...

  16. 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

  17. 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

  18. Comparison of reflectance confocal microscopy and two-photon second harmonic generation microscopy in fungal keratitis rabbit model ex vivo

    PubMed Central

    Lee, Jun Ho; Lee, Seunghun; Yoon, Calvin J.; Park, Jin Hyoung; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

    2016-01-01

    Fungal keratitis is an infection of the cornea by fungal pathogens. Diagnosis methods based on optical microscopy could be beneficial over the conventional microbiology method by allowing rapid and non-invasive examination. Reflectance confocal microscopy (RCM) and two-photon second harmonic generation microscopy (TPSHGM) have been applied to pre-clinical or clinical studies of fungal keratitis. In this report, RCM and TPSHGM were characterized and compared in the imaging of a fungal keratitis rabbit model ex vivo. Fungal infection was induced by using two strains of fungi: aspergillus fumigatus and candida albicans. The infected corneas were imaged in fresh condition by both modalities sequentially and their images were analyzed. Both RCM and TPSHGM could detect both fungal strains within the cornea based on morphology: aspergillus fumigatus had distinctive filamentous structures, and candida albicans had round structures superficially and elongated structures in the corneal stroma. These imaging results were confirmed by histology. Comparison between RCM and TPSHGM showed several characteristics. Although RCM and TPSHGM images had good correlation each other, their images were slightly different due to difference in contrast mechanism. RCM had relatively low image contrast with the infected turbid corneas due to high background signal. TPSHGM visualized cells and collagen in the cornea clearly compared to RCM, but used higher laser power to compensate low autofluorescence. Since these two modalities provide complementary information, combination of RCM and TPSHGM would be useful for fungal keratitis detection by compensating their weaknesses each other. PMID:26977371

  19. Comparison of reflectance confocal microscopy and two-photon second harmonic generation microscopy in fungal keratitis rabbit model ex vivo.

    PubMed

    Lee, Jun Ho; Lee, Seunghun; Yoon, Calvin J; Park, Jin Hyoung; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

    2016-02-01

    Fungal keratitis is an infection of the cornea by fungal pathogens. Diagnosis methods based on optical microscopy could be beneficial over the conventional microbiology method by allowing rapid and non-invasive examination. Reflectance confocal microscopy (RCM) and two-photon second harmonic generation microscopy (TPSHGM) have been applied to pre-clinical or clinical studies of fungal keratitis. In this report, RCM and TPSHGM were characterized and compared in the imaging of a fungal keratitis rabbit model ex vivo. Fungal infection was induced by using two strains of fungi: aspergillus fumigatus and candida albicans. The infected corneas were imaged in fresh condition by both modalities sequentially and their images were analyzed. Both RCM and TPSHGM could detect both fungal strains within the cornea based on morphology: aspergillus fumigatus had distinctive filamentous structures, and candida albicans had round structures superficially and elongated structures in the corneal stroma. These imaging results were confirmed by histology. Comparison between RCM and TPSHGM showed several characteristics. Although RCM and TPSHGM images had good correlation each other, their images were slightly different due to difference in contrast mechanism. RCM had relatively low image contrast with the infected turbid corneas due to high background signal. TPSHGM visualized cells and collagen in the cornea clearly compared to RCM, but used higher laser power to compensate low autofluorescence. Since these two modalities provide complementary information, combination of RCM and TPSHGM would be useful for fungal keratitis detection by compensating their weaknesses each other. PMID:26977371

  20. [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. PMID:21420576

  1. 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. PMID:26739604

  2. Acute Bronchitis

    MedlinePlus

    ... or though physical contact (for example, on unwashed hands). Being exposed to tobacco smoke, air pollution, dusts, vapors, and fumes can also cause acute bronchitis. Less often, bacteria can also cause acute bronchitis. To diagnose acute ...

  3. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... control. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  4. Regulation of the fungal secretome.

    PubMed

    McCotter, Sean W; Horianopoulos, Linda C; Kronstad, James W

    2016-08-01

    The ability of countless representatives of the Kingdom Fungi to adapt to and proliferate in diverse environments is facilitated by regulation of their secretomes to respond to changes in environmental conditions and to mediate interactions with other organisms. Secretome changes often fulfill common functions of nutrient acquisition, facilitation of host/symbiont interactions, cell wall modification, and optimization of the enzyme suite to adapt to new environmental resources. In this review, we expand on our recent work on signaling and the secretome in the pathogenic fungus Cryptococcus neoformans to consider a range of selected examples of regulation of fungal secretomes. These examples include the impact of carbon source and aspects of the response to plant and animal hosts. Additionally, the influence of key protein kinases (e.g., Pka1, Snf1) and transcription factors (e.g., Rim101/PacC) is highlighted to illustrate some underlying regulatory factors influencing the secretome. Although there is a wealth of information about fungal secretomes from both experimentation and genome sequence mining, there are also major gaps in our knowledge about the complete composition of fungal secretomes and mechanisms of dynamic change. For example, a more comprehensive understanding of the composition and regulation of the secretome will require consideration of the emerging roles of unconventional secretion and extracellular vesicles in delivering proteins outside the cell. Overall, changes in the secretome are well documented in diverse fungi and the underlying mechanisms are currently under investigation; however, there remain unknown steps in the regulation of secretory pathways and gaps in understanding the regulation of unconventional secretion, which warrant further research. PMID:26879194

  5. 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

    2016-03-01

    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. PMID:26922990

  6. 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

  7. 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

  8. 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

  9. Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis

    PubMed Central

    Dagenais, Taylor R. T.; Keller, Nancy P.

    2009-01-01

    Summary: Aspergillus species are globally ubiquitous saprophytes found in a variety of ecological niches. Almost 200 species of aspergilli have been identified, less than 20 of which are known to cause human disease. Among them, Aspergillus fumigatus is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis (IA) in the immunocompromised patient population. IA is a devastating illness, with mortality rates in some patient groups reaching as high as 90%. Studies identifying and assessing the roles of specific factors of A. fumigatus that contribute to the pathogenesis of IA have traditionally focused on single-gene deletion and mutant characterization. In combination with recent large-scale approaches analyzing global fungal responses to distinct environmental or host conditions, these studies have identified many factors that contribute to the overall pathogenic potential of A. fumigatus. Here, we provide an overview of the significant findings regarding A. fumigatus pathogenesis as it pertains to invasive disease. PMID:19597008

  10. POSSIBLE ROLE OF FUNGAL HEMOLYSINS IN SICK BUILDING SYNDROME

    EPA Science Inventory

    Many fungi produce proteinaceous hemolytic agents. Like bacterial hemolysins, fungal hemolysins create pores or holes in membranes. Depending on which membranes are damaged, fungal hemolysins can produce a variety of effects. Fungal hemolysins can cause histamine release from ...

  11. Fungal Septicemia in Surgical Patients

    PubMed Central

    Rodrigues, Roberto J.; Wolff, William I.

    1974-01-01

    Opportunistic systemic fungal infections are more frequent than generally realized. Increased awareness and a high index of suspicion of fungal super-infection in the presence of sepsis is required to bring about recognition and therapy. The intravenous catheter is an important portal of entry or may act as a foreign body favoring localization of a septic process. In its presence, fungemia must be guarded against. Whenever an intravenous catheter is removed, its tip should be cultured. Removal alone may be a critical item in therapy. In febrile patients, in whom the course of fever is not established, frequent blood cultures with attention directed specifically at fungi should be obtained. Fungi are not easily isolated and identified and only by requesting special attention from the microbiologist can the diagnosis be established in the average institutional laboratory in time to permit appropriate therapy. Since available therapeutic measures are strikingly effective when instituted early, awareness and alertness on the part of the clinician constitute the key to cure. PMID:4213622

  12. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning - A Rare Complication.

    PubMed

    Kamarthi, Prabhakar; Subramani, Parimala; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-06-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  13. Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous Compound Poisoning – A Rare Complication

    PubMed Central

    Kamarthi, Prabhakar; Gopu, Arun Vardharaju; Prasad, Reddy; Srinivasa, Chandrakala

    2016-01-01

    We report a case of acute pancreatitis and hepatitis following ingestion of yellow phosphorous. The condition of the patient progressed to encephalopathy and bony erosion of the nasal septum. Fungal mass was observed in both the nasal cavities by endoscopy. Microbiological investigation revealed the identity of the fungus as Aspergillus flavus and Candida tropicalis. Patient improved with fluconazole treatment. PMID:27504287

  14. Naming names: the etymology of fungal entomopathogens.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chapter introduces the reader to the etymology of the generic names given to 26 fungal entomopathogens. Possessing some knowledge on how a name originates sometimes provides us with information on a fungal characteristic that might help us identify the organism, e.g., Conidiobolus, Cordyceps, P...

  15. Fungal endophytes in green coffee seeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Green coffee seeds from Colombia, Guatemala, India, Kenya, Papua New Guinea, Puerto Rico, and Vietnam were sampled for the presence of fungal endophytes. Sections of surface sterilized seeds were plated on yeast malt agar, and fungal growth was isolated for subsequent DNA extraction and sequencing....

  16. Renal fungal bezoar owing to Geotrichum candidum

    PubMed Central

    Yegneswaran Prakash, Peralam; Seetaramaiah, Venkatesh K; Thomas, Joseph; Khanna, Vinay; Rao, Sugandhi P

    2012-01-01

    Geotrichum candidum is yeast like fungi that cause infections in immunocompromised patients. We report a case of renal fungal ball with Geotrichum candidum in a 27 yr. old women post-partum. This case to our knowledge is the first case of renal fungal bezoar due to Geotrichum candidum reported in India.

  17. Industrial Fungal Enzymes: An Occupational Allergen Perspective

    PubMed Central

    Green, Brett J.; Beezhold, Donald H.

    2011-01-01

    Occupational exposure to high-molecular-weight allergens is a risk factor for the development and pathogenesis of IgE-mediated respiratory disease. In some occupational environments, workers are at an increased risk of exposure to fungal enzymes used in industrial production. Fungal enzymes have been associated with adverse health effects in the work place, in particular in baking occupations. Exposure-response relationships have been demonstrated, and atopic workers directly handling fungal enzymes are at an increased risk for IgE-mediated disease and occupational asthma. The utilization of new and emerging fungal enzymes in industrial production will present new occupational exposures. The production of antibody-based immunoassays is necessary for the assessment of occupational exposure and the development of threshold limit values. Allergen avoidance strategies including personal protective equipment, engineering controls, protein encapsulation, and reduction of airborne enzyme concentrations are required to mitigate occupational exposure to fungal enzymes. PMID:21747869

  18. Fungal natural products in research and development.

    PubMed

    Schueffler, Anja; Anke, Timm

    2014-10-01

    To date approximately 100 000 fungal species are known although far more than one million are expected. The variety of species and the diversity of their habitats, some of them less exploited, allow the conclusion that fungi continue to be a rich source of new metabolites. Besides the conventional fungal isolates, an increasing interest in endophytic and in marine-derived fungi has been noticed. In addition new screening strategies based on innovative chemical, biological, and genetic approaches have led to novel fungal metabolites in recent years. The present review focuses on new fungal natural products published from 2009 to 2013 highlighting the originality of the structures and their biological potential. Furthermore synthetic products based on fungal metabolites as well as new developments in the uses or the biological activity of known compounds or new derivatives are discussed. PMID:25122538

  19. Histone Acetylation in Fungal Pathogens of Plants

    PubMed Central

    Jeon, Junhyun; Kwon, Seomun; Lee, Yong-Hwan

    2014-01-01

    Acetylation of histone lysine residues occurs in different organisms ranging from yeast to plants and mammals for the regulation of diverse cellular processes. With the identification of enzymes that create or reverse this modification, our understanding on histone acetylation has expanded at an amazing pace during the last two decades. In fungal pathogens of plants, however, the importance of such modification has only just begun to be appreciated in the recent years and there is a dearth of information on how histone acetylation is implicated in fungal pathogenesis. This review covers the current status of research related to histone acetylation in plant pathogenic fungi and considers relevant findings in the interaction between fungal pathogens and host plants. We first describe the families of histone acetyltransferases and deacetylases. Then we provide the cases where histone acetylation was investigated in the context of fungal pathogenesis. Finally, future directions and perspectives in epigenetics of fungal pathogenesis are discussed. PMID:25288980

  20. [Serious bacterial and fungal infections in intravenous drug addicts].

    PubMed

    Jensenius, M; Heger, B; Dalgard, O; Stiris, M; Ringertz, S H

    1999-05-10

    Invasive infections caused by bacteria and fungi are common complications of intravenous drug abuse. Various vital organs and structures may be affected, e.g. the cardiac valves, the larger arteries, the bones, the joints and the central nervous system. However, due to the high frequency of low-virulent microbes of skin and oral origin, the clinical picture may be atypical with subacute course and few focal signs and symptoms. The complexity of this problem is illustrated by eight cases of serious bacterial and fungal infections recently diagnosed at our hospitals. All patients were HIV negative intravenous heroin addicts. The clinical spectrum was wide and included skin abscesses, pyomyositis, spondylodiscitis, septic arthritis, costal osteomyelitis, infective endocarditis, recurrent bacteraemia, and multiple brain abscesses. PMID:10380592

  1. Syk Signaling in Dendritic Cells Orchestrates Innate Resistance to Systemic Fungal Infection

    PubMed Central

    Osorio, Fabiola; Rogers, Neil C.; Schraml, Barbara U.; Deddouche, Safia; LeibundGut-Landmann, Salomé; Reis e Sousa, Caetano

    2014-01-01

    Host protection from fungal infection is thought to ensue in part from the activity of Syk-coupled C-type lectin receptors and MyD88-coupled toll-like receptors in myeloid cells, including neutrophils, macrophages and dendritic cells (DCs). Given the multitude of cell types and receptors involved, elimination of a single pathway for fungal recognition in a cell type such as DCs, primarily known for their ability to prime T cell responses, would be expected to have little effect on innate resistance to fungal infection. Here we report that this is surprisingly not the case and that selective loss of Syk but not MyD88 in DCs abrogates innate resistance to acute systemic Candida albicans infection in mice. We show that Syk expression by DCs is necessary for IL-23p19 production in response to C. albicans, which is essential to transiently induce GM-CSF secretion by NK cells that are recruited to the site of fungal replication. NK cell-derived-GM-CSF in turn sustains the anti-microbial activity of neutrophils, the main fungicidal effectors. Thus, the activity of a single kinase in a single myeloid cell type orchestrates a complex series of molecular and cellular events that underlies innate resistance to fungal sepsis. PMID:25033445

  2. Opportunistic fungal and bacterial infection in the renal transplant recipient.

    PubMed

    Tolkoff-Rubin, N E; Rubin, R H

    1992-06-01

    The risk of opportunistic infection in the renal transplant recipient is determined by the interaction between two factors: the epidemiologic exposures the individual encounters within the community and the hospital and a complex function termed the net state of immunosuppression. There are two general categories of opportunistic fungal infection in this patient population: (1) disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis) and (2) opportunistic infection with fungal species that rarely cause invasive infection in the normal host (Aspergillus species, Candida species, Cryptococcus neoformans, and the Mucoraceae), with these last usually being acquired within the hospital environment. Newly available azole compounds, fluconazole and itraconazole, are exciting new alternatives to amphotericin in the treatment of at least some of these infections. The three most important forms of opportunistic bacterial infections are those due to Listeria monocytogenes, Nocardia asteroides, and a variety of mycobacterial species. Clinical diseases with these first two are effectively prevented by low-dose trimethoprim-sulfamethoxazole prophylaxis. There are two cardinal therapeutic rules to be followed by clinicians in dealing with these infections: prevention is better than treatment; when treatment is required, however, the major determinant of the success of therapy is the rapidity with which the diagnosis is made and effective therapy is initiated. PMID:1498286

  3. Hydrodynamics, Fungal Physiology, and Morphology.

    PubMed

    Serrano-Carreón, L; Galindo, E; Rocha-Valadéz, J A; Holguín-Salas, A; Corkidi, G

    2015-01-01

    Filamentous cultures, such as fungi and actinomycetes, contribute substantially to the pharmaceutical industry and to enzyme production, with an annual market of about 6 billion dollars. In mechanically stirred reactors, most frequently used in fermentation industry, microbial growth and metabolite productivity depend on complex interactions between hydrodynamics, oxygen transfer, and mycelial morphology. The dissipation of energy through mechanically stirring devices, either flasks or tanks, impacts both microbial growth through shearing forces on the cells and the transfer of mass and energy, improving the contact between phases (i.e., air bubbles and microorganisms) but also causing damage to the cells at high energy dissipation rates. Mechanical-induced signaling in the cells triggers the molecular responses to shear stress; however, the complete mechanism is not known. Volumetric power input and, more importantly, the energy dissipation/circulation function are the main parameters determining mycelial size, a phenomenon that can be explained by the interaction of mycelial aggregates and Kolmogorov eddies. The use of microparticles in fungal cultures is also a strategy to increase process productivity and reproducibility by controlling fungal morphology. In order to rigorously study the effects of hydrodynamics on the physiology of fungal microorganisms, it is necessary to rule out the possible associated effects of dissolved oxygen, something which has been reported scarcely. At the other hand, the processes of phase dispersion (including the suspended solid that is the filamentous biomass) are crucial in order to get an integral knowledge about biological and physicochemical interactions within the bioreactor. Digital image analysis is a powerful tool for getting relevant information in order to establish the mechanisms of mass transfer as well as to evaluate the viability of the mycelia. This review focuses on (a) the main characteristics of the two most

  4. 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

  5. Innate Defense against Fungal Pathogens

    PubMed Central

    Drummond, Rebecca A.; Gaffen, Sarah L.; Hise, Amy G.; Brown, Gordon D.

    2014-01-01

    Human fungal infections have been on the rise in recent years and proved increasingly difficult to treat as a result of the lack of diagnostics, effective antifungal therapies, and vaccines. Most pathogenic fungi do not cause disease unless there is a disturbance in immune homeostasis, which can be caused by modem medical interventions, disease induced immunosuppression, and naturally occurring human mutations. The innate im mune system is weII equipped to recognize and destroy pathogeni cf ungi through speciaIized cells expressing a broad range of pattern recognition receptors (PRRs). This review will outline the cells and PRRs required for effective antifungal immunity, with a special focus on the major antifungal cytokine IL-17 and recently characterized antifungal inflammasomes. PMID:25384766

  6. Dancing genomes: fungal nuclear positioning

    PubMed Central

    Gladfelter, Amy; Berman, Judith

    2009-01-01

    The many different mechanisms that fungi use to transmit and share genetic material are mediated by a broad range of chromosome and nuclear dynamics. The mechanics underlying nuclear migration are well integrated into detailed models, in which the forces supplied by plus- and minus-end-directed microtubule motors position and move the nucleus in a cell. Although we know much about how cells move nuclei, we know much less about why the cell invests in so many different nuclear ‘dances’. Here, we briefly survey the available models for the mechanics of nuclear migration in fungi and then focus on examples of how fungal cells use these nuclear dances — the movement of intact nuclei in and between cells — to control the integrity, ploidy and assortment of specific genomes or individual chromosomes. PMID:19898490

  7. Classification of fungal chitin synthases.

    PubMed Central

    Bowen, A R; Chen-Wu, J L; Momany, M; Young, R; Szaniszlo, P J; Robbins, P W

    1992-01-01

    Comparison of the chitin synthase genes of Saccharomyces cerevisiae CHS1 and CHS2 with the Candida albicans CHS1 gene (UDP-N-acetyl-D-glucosamine:chitin 4-beta-N-acetylglucosaminyltransferase, EC 2.4.1.16) revealed two small regions of complete amino acid sequence conservation that were used to design PCR primers. Fragments homologous to chitin synthase (approximately 600 base pairs) were amplified from the genomic DNA of 14 fungal species. These fragments were sequenced, and their deduced amino acid sequences were aligned. With the exception of S. cerevisiae CHS1, the sequences fell into three distinct classes, which could represent separate functional groups. Within each class phylogenetic analysis was performed. Although not the major purpose of the investigation, this analysis tends to confirm some relationships consistent with current taxonomic groupings. Images PMID:1731323

  8. Invasion dynamics of white-nose syndrome fungus, midwestern United States, 2012-2014.

    PubMed

    Langwig, Kate E; Hoyt, Joseph R; Parise, Katy L; Kath, Joe; Kirk, Dan; Frick, Winifred F; Foster, Jeffrey T; Kilpatrick, A Marm

    2015-06-01

    White-nose syndrome has devastated bat populations in eastern North America. In Midwestern United States, prevalence increased quickly in the first year of invasion (2012-13) but with low population declines. In the second year (2013-14), environmental contamination led to earlier infection and high population declines. Interventions must be implemented before or soon after fungal invasion to prevent population collapse. PMID:25989230

  9. Invasion Dynamics of White-Nose Syndrome Fungus, Midwestern United States, 2012–2014

    PubMed Central

    Langwig, Kate E.; Hoyt, Joseph R.; Parise, Katy L.; Kath, Joe; Kirk, Dan; Frick, Winifred F.; Foster, Jeffrey T.

    2015-01-01

    White-nose syndrome has devastated bat populations in eastern North America. In Midwestern United States, prevalence increased quickly in the first year of invasion (2012–13) but with low population declines. In the second year (2013–14), environmental contamination led to earlier infection and high population declines. Interventions must be implemented before or soon after fungal invasion to prevent population collapse. PMID:25989230

  10. A neonatal case of chronic granulomatous disease, initially presented with invasive pulmonary aspergillosis.

    PubMed

    Saito, Sachiko; Oda, Arata; Kasai, Masashi; Minami, Kisei; Nagumo, Haruo; Shiohara, Masaaki; Ogiso, Yoshifumi; Kawakami, Yoshiyuki

    2014-03-01

    Chronic granulomatous disease (CGD) often presents with infectious illness, such as repeating bacterial and fungal infections, due to the inability to generate superoxide, which would destroy certain infectious pathogens, and is usually diagnosed in childhood. We describe a CGD case diagnosed in neonatal period, who initially presented with invasive aspergillosis. Neonatal invasive pulmonary aspergillosis is very rare and, to the best of our knowledge, this might be the youngest case in Japan. PMID:24674387

  11. The Rise of an Oppurtunistic Infection called “Invasive Zygomycosis”

    PubMed Central

    Waness, Abdelkarim; Dawsari, Ghuzayel Al; Jahdali, Hamdan Al

    2009-01-01

    Invasive zygomycosis is a devastating fungal infection seen mostly in immune-compromised patients. We present a case of a 48-year old diabetic man, with aplastic anemia, who developed severe pulmonary mucormycosis that led to his rapid demise despite early diagnosis and treatment with liposomal amphotericin B. We also conducted an extensive review of the pathogenesis of invasive zygomycosis, its history, predisposing factors, clinical aspects, diagnostic modalities, treatment options, morbidity and mortality. PMID:20300403

  12. Enhanced fungal DNA-Extraction from Formalin fixed, paraffin embedded tissue specimens by application of thermal energy

    PubMed Central

    Rickerts, V.; Khot, P.D.; Ko, D.L.; Fredricks, D.N.

    2014-01-01

    Summary Determining the etiology of invasive fungal infections (IFI) is critical for patient management as fungi vary in their susceptibility to antifungals. However, the etiology remains obscure in many cases due to negative culture results. The identification of fungal DNA from pathology blocks by PCR and sequencing is an alternative approach to determine the etiology of IFI. Previous studies identified fungal DNA in only 50% of samples with positive histopathology, probably due to DNA damage by the tissue fixation. We used realtime PCR to quantify human and fungal DNA from Formalin-fixed, paraffin embedded tissue specimens in order to study the effect of thermal energy during extraction on the yield of amplifiable DNA and subsequent identification of fungal DNA. Tissue sections from eight patients with proven IFI were subjected to DNA extraction with varying exposure to thermal energy. Amplifiable DNA increased up to 76-fold by increasing incubation temperature from 65°C to 90°C. An additional increase was documented by incubation for up to 6 hours at 90°C. The augmented amplification of fungal DNA was associated with improved species identification by sequencing of the PCR amplicons. This may help illuminate the etiology of IFI and thereby improve patient management by guiding antifungal therapy. PMID:22414380

  13. DAMP signaling in fungal infections and diseases

    PubMed Central

    Cunha, Cristina; Carvalho, Agostinho; Esposito, Antonella; Bistoni, Francesco; Romani, Luigina

    2012-01-01

    Fungal infections and diseases predominantly affect patients with deregulated immunity. Compelling experimental and clinical evidence indicate that severe fungal diseases belong to the spectrum of fungus-related inflammatory diseases. Some degree of inflammation is required for protection during the transitional response occurring temporally between the rapid innate and slower adaptive response. However, progressive inflammation worsens disease and ultimately prevents pathogen eradication. The challenge now is to elucidate cellular and molecular pathways distinguishing protective vs. pathogenic inflammation to fungi. In addition to fungal ligands of pattern recognition receptors (pathogen-associated molecular patterns, PAMPs), several host-encoded proteins, the damage-associated molecular patterns (DAMPs), are released during tissue injury and activate innate recognition receptors. DAMPs have been shown to regulate inflammation in fungal diseases. The DAMP/receptor for advanced glycation end-products axis integrated with the PAMP/Toll-like receptors axis in the generation of the inflammatory response in experimental and clinical fungal pneumonia. These emerging themes better accommodate fungal pathogenesis in the face of high-level inflammation seen in several clinical settings and point to DAMP targeting as a novel immunomodulatory strategy in fungal diseases. PMID:22973279

  14. Fungal genome sequencing: basic biology to biotechnology.

    PubMed

    Sharma, Krishna Kant

    2016-08-01

    The genome sequences provide a first glimpse into the genomic basis of the biological diversity of filamentous fungi and yeast. The genome sequence of the budding yeast, Saccharomyces cerevisiae, with a small genome size, unicellular growth, and rich history of genetic and molecular analyses was a milestone of early genomics in the 1990s. The subsequent completion of fission yeast, Schizosaccharomyces pombe and genetic model, Neurospora crassa initiated a revolution in the genomics of the fungal kingdom. In due course of time, a substantial number of fungal genomes have been sequenced and publicly released, representing the widest sampling of genomes from any eukaryotic kingdom. An ambitious genome-sequencing program provides a wealth of data on metabolic diversity within the fungal kingdom, thereby enhancing research into medical science, agriculture science, ecology, bioremediation, bioenergy, and the biotechnology industry. Fungal genomics have higher potential to positively affect human health, environmental health, and the planet's stored energy. With a significant increase in sequenced fungal genomes, the known diversity of genes encoding organic acids, antibiotics, enzymes, and their pathways has increased exponentially. Currently, over a hundred fungal genome sequences are publicly available; however, no inclusive review has been published. This review is an initiative to address the significance of the fungal genome-sequencing program and provides the road map for basic and applied research. PMID:25721271

  15. A novel class of fungal lipoxygenases.

    PubMed

    Heshof, Ruud; Jylhä, Sirpa; Haarmann, Thomas; Jørgensen, Ann Louise Worsøe; Dalsgaard, Trine Kastrup; de Graaff, Leo H

    2014-02-01

    Lipoxygenases (LOXs) are well-studied enzymes in plants and mammals. However, fungal LOXs are less studied. In this study, we have compared fungal LOX protein sequences to all known characterized LOXs. For this, a script was written using Shell commands to extract sequences from the NCBI database and to align the sequences obtained using Multiple Sequence Comparison by Log-Expectation. We constructed a phylogenetic tree with the use of Quicktree to visualize the relation of fungal LOXs towards other LOXs. These sequences were analyzed with respect to the signal sequence, C-terminal amino acid, the stereochemistry of the formed oxylipin, and the metal ion cofactor usage. This study shows fungal LOXs are divided into two groups, the Ile- and the Val-groups. The Ile-group has a conserved WRYAK sequence that appears to be characteristic for fungal LOXs and has as a C-terminal amino acid Ile. The Val-group has a highly conserved WL-L/F-AK sequence that is also found in LOXs of plant and animal origin. We found that fungal LOXs with this conserved sequence have a Val at the C-terminus in contrast to other LOXs of fungal origin. Also, these LOXs have signal sequences implying these LOXs will be expressed extracellularly. Our results show that in this group, in addition to the Gaeumannomyces graminis and the Magnaporthe salvinii LOXs, the Aspergillus fumigatus LOX uses manganese as a cofactor. PMID:24276623

  16. Allergic fungal otomastoiditis: a case report.

    PubMed

    Chen, Chiung-Ming; Chiang, Ching-Wen

    2013-04-01

    Allergic mucin is described as thick, peanut butter-like mucus impacted in the paranasal sinuses of patients with allergic fungal rhinosinusitis. The presence of allergic mucin in the middle ear has never been reported. We encountered a 65-year-old female with allergic mucin found impacted in her left middle ear and mastoid cavity during revised tympanoplasty surgery at our institute. Bilateral endoscopic sinus surgery performed 3 months later showed no evidence of fungal infection or allergic mucin in her paranasal sinuses. We report the case herein and propose the term allergic fungal otomastoiditis for this disease entity. PMID:22825725

  17. Fungal glycans and the innate immune recognition

    PubMed Central

    Barreto-Bergter, Eliana; Figueiredo, Rodrigo T.

    2014-01-01

    Polysaccharides such as α- and β-glucans, chitin, and glycoproteins extensively modified with both N- and O-linked carbohydrates are the major components of fungal surfaces. The fungal cell wall is an excellent target for the action of antifungal agents, since most of its components are absent from mammalian cells. Recognition of these carbohydrate-containing molecules by the innate immune system triggers inflammatory responses and activation of microbicidal mechanisms by leukocytes. This review will discuss the structure of surface fungal glycoconjugates and polysaccharides and their recognition by innate immune receptors. PMID:25353009

  18. The clinical importance of fungal biofilms.

    PubMed

    Ramage, Gordon; Williams, Craig

    2013-01-01

    Fungal biofilms have become an increasingly important clinical problem. The widespread use of antibiotics, frequent use of indwelling medical devices, and a trend toward increased patient immunosuppression have resulted in a creation of opportunity for clinically important yeasts and molds to form biofilms. This review will discuss the diversity and importance of fungal biofilms in the context of clinical medicine, provide novel insights into the clinical management of fungal biofilm infection, present evidence why these structures are recalcitrant to antifungal therapy, and discuss how our knowledge and understanding may lead to novel therapeutic intervention. PMID:23763758

  19. 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.

  20. Expanding Fungal Diets Through Synthetic Algal-Fungal Mutualism

    NASA Technical Reports Server (NTRS)

    Sharma, Alaisha; Galazka, Jonathan (Editor)

    2015-01-01

    Fungi can synthesize numerous molecules with important properties, and could be valuable production platforms for space exploration and colonization. However, as heterotrophs, fungi require reduced carbon. This limits their efficiency in locations such as Mars, where reduced carbon is scarce. We propose a system to induce mutualistic symbiosis between the green algae Chlamydomonas reinhardtii and the filamentous fungi Neurospora crassa. This arrangement would mimic natural algal-fungal relationships found in lichens, but have added advantages including increased growth rate and genetic tractability. N. crassa would metabolize citrate (C6H5O7 (sup -3)) and release carbon dioxide (CO2) that C. reinhardtii would assimilate into organic sugars during photosynthesis. C. reinhardtii would metabolize nitrate (NO3-) and release ammonia (NH3) as a nitrogen source for N. crassa. A N. crassa mutant incapable of reducing nitrate will be used to force this interaction. This system eliminates the need to directly supply its participants with carbon dioxide and ammonia. Furthermore, the release of oxygen by C. reinhardtii via photosynthesis would enable N. crassa to respire. We hope to eventually create a system closer to lichen, in which the algae transfers not only nitrogen but reduced carbon, as organic sugars, to the fungus for growth and production of valuable compounds.

  1. Death by edible mushroom: first report of Volvariella volvacea as an etiologic agent of invasive disease in a patient following double umbilical cord blood transplantation.

    PubMed

    Salit, R B; Shea, Y R; Gea-Banacloche, J; Fahle, G A; Abu-Asab, M; Sugui, J A; Carpenter, A E; Quezado, M M; Bishop, M R; Kwon-Chung, K J

    2010-11-01

    We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales. PMID:20826647

  2. PNNL Fungal Biotechnology Core DOE-OBP Project

    SciTech Connect

    Baker, Scott E.; Bruno, Kenneth S.; Butcher, Mark G.; Collett, James R.; Culley, David E.; Dai, Ziyu; Magnuson, Jon K.; Panisko, Ellen A.

    2009-11-30

    In 2009, we continued to address barriers to fungal fermentation in the primary areas of morphology control, genomics, proteomics, fungal hyperproductivity, biomass-to-products via fungal based consolidated bioprocesses, and filamentous fungal ethanol. “Alternative renewable fuels from fungi” was added as a new subtask. Plans were also made to launch a new advanced strain development subtask in FY2010.

  3. Emergent fungal entomopathogen does not alter density dependence in a viral competitor.

    PubMed

    Liebhold, Andrew M; Plymale, Ruth; Elkinton, Joseph S; Hajek, Ann E

    2013-06-01

    Population cycles in forest Lepidoptera often result from recurring density-dependent epizootics of entomopathogens. While these systems are typically dominated by a single pathogen species, insects are often infected by multiple pathogens, yet little is known how pathogens interact to affect host dynamics. The apparent invasion of northeastern North America by the fungal entomopathogen Entomophaga maimaiga some time prior to 1989 provides a unique opportunity to evaluate such interactions. Prior to the arrival of E. maimaga, the oscillatory dynamics of host gypsy moth, Lymantria dispar, populations were apparently driven by epizootics of a nucleopolyhedrovirus. Subsequent to its emergence, E. maimaiga has caused extensive mortality in host populations, but little is known about how it has altered multigenerational dynamics of the gypsy moth and its virus. Here we compared demographic data collected in gypsy moth populations prior to vs. after E. maimaiga's invasion. We found that the recently invading fungal pathogen virtually always causes greater levels of mortality in hosts than does the virus, but fungal mortality is largely density independent. Moreover, the presence of the fungus has apparently not altered the gypsy moth-virus density-dependent interactions that were shown to drive periodic oscillations in hosts before the arrival of the fungus. PMID:23923480

  4. Imaging O2 changes induced in tomato roots by fungal pathogen

    NASA Astrophysics Data System (ADS)

    Rubol, S.; Turco, E.; Rodeghiero, M.; Bellin, A.

    2014-12-01

    In the last decade, planar optodes have demonstrated to be a useful non-invasive tool to monitor real time oxygen concentrations in a wide range of applications. However, only limited investigations have been carried out to explore the use of optodes in plant respiration studies. In particular, their use to study plant-pathogen interactions has been not deeply investigated. Here, we present for the first time an in vitro experimental setup capable to depict the dynamical effects of the fungal pathogen Fusarium oxysporum f.sp. lycopersici (Fol) on tomato roots by the use of a recently developed optical non-invasive optode oxygen sensor (Visisens, Presens, Germany). Fol is a soil-borne pathogen and the causal agent of wilt in tomato plants, a destructive worldwide disease. The interaction Fol-tomato is widely accepted as a model system in plant pathology. In this work, oxygen concentrations are monitored continuously in time and considered a proxy for root respiration and metabolic activity. The experimental procedure reveals three different dynamic stages: 1) a uniform oxygen consumption in tomato roots earlier before pathogen colonization, 2) a progressive decrease in the oxygen concentration indicating a high metabolic activity as soon as the roots were surrounded and colonized by the fungal mycelium, and 3) absence of root respiration, as a consequence of root death. Our results suggest the ability of the fungal mycelium to move preferentially towards and along the root as a consequence of the recognition event.

  5. Opportunistic fungal infections in the Asia-Pacific region.

    PubMed

    Slavin, Monica A; Chakrabarti, Arunaloke

    2012-01-01

    With more than half the world's population, many Asia-Pacific countries still lack resources for adequate infection control and diagnostics. Opportunistic invasive fungal infections (IFIs) have a significant impact on public health in the region, and early diagnosis and appropriate treatment remain important. The incidence of IFI in the Asia-Pacific region is increasing because of the expanded population of immunosuppressed patients resulting from advances in medical technology, such as treatments for cancer and transplantation, as well as the impact of human immunodeficiency virus. Even so, the epidemiology of IFIs is not well described in the Asia-Pacific region. Prevalence of some infections, such as mucormycosis, is particularly related to undiagnosed or untreated diabetes, which is likely to be a continuing problem with the epidemic of diabetes in the region. In addition, despite some effective treatment options, IFIs are associated with high morbidity and mortality. In an attempt to increase recognition of invasive mycoses in this large area, this paper reviews recent findings on the epidemiology of the most clinically significant opportunistic mould and yeast infections in the Asia-Pacific region, i.e., aspergillosis, mucormycosis, pythiosis, scedosporiosis, fusariosis, candidiasis, trichosporonosis, and cryptococcosis. PMID:21905945

  6. Analysis of fungal ball rhinosinusitis by culturing fungal clumps under endoscopic surgery

    PubMed Central

    Zhang, Junyi; Li, Yunchuan; Lu, Xinxin; Wang, Xiangdong; Zang, Hongrui; Wang, Tong; Zhou, Bing; Zhang, Luo

    2015-01-01

    Objective: This study was designed to investigate the clinical microbiology of fungal ball (FB) rhinosinusitis by culturing fungal clumps collected under endoscopic surgery. Methods: From April to November of 2012, fungal clumps were sampled by endoscopic surgery from patients diagnosed with FB using clinical and histopathological methods. The specimens were subjected to smear microscopy, and cultured for bacteria and fungi analysis. Results: Out of the 81 specimens from 80 patients, 69 (69/81, 85.19%) specimens were detected a mixed infection of bacteria and fungi. However, only 25 (25/81, 30.86%) specimens resulted in fungal growth. There were 12 (12/81, 14.81%) specimens with fungal infections alone. The cultured fungi included 36 strains belonging to five genera, and most of them were Aspergillus spp. (30/36, 83.3%). The cultured bacteria included 94 strains belonging to 16 genera, and the most frequently seen was Staphylococcus spp. (23/94, 35.94%). When it was fungal and Pseudomonas aeruginosa mixed infection, the fungal growth was inhibited (P = 0.002). Conclusion: Patients with fungal ball usually have mixed fungal and bacterial infections. The fungi from these samples are sometimes difficult to culture, which may be the result of the inhibition by bacteria in vitro and in vivo. PMID:26131186

  7. (Post-)genomics approaches in fungal research.

    PubMed

    Aguilar-Pontes, María Victoria; de Vries, Ronald P; Zhou, Miaomiao

    2014-11-01

    To date, hundreds of fungal genomes have been sequenced and many more are in progress. This wealth of genomic information has provided new directions to study fungal biodiversity. However, to further dissect and understand the complicated biological mechanisms involved in fungal life styles, functional studies beyond genomes are required. Thanks to the developments of current -omics techniques, it is possible to produce large amounts of fungal functional data in a high-throughput fashion (e.g. transcriptome, proteome, etc.). The increasing ease of creating -omics data has also created a major challenge for downstream data handling and analysis. Numerous databases, tools and software have been created to meet this challenge. Facing such a richness of techniques and information, hereby we provide a brief roadmap on current wet-lab and bioinformatics approaches to study functional genomics in fungi. PMID:25037051

  8. Air Contamination With Fungals In Museum

    NASA Astrophysics Data System (ADS)

    Scarlat, Iuliana; Haiducu, Maria; Stepa, Raluca

    2015-07-01

    The aim of the studies was to determine the level and kind of fungal contamination of air in museum, deposits patrimony, restoration and conservation laboratories and their effects on health of workers. Microbiological air purity was measured with a SAS-100 Surface Air System impactor. The fungal contamination was observed in all 54 rooms where we made determinations. The highest levels of fungal were recorded at rooms with hygroscopic patrimony objects, eg carpets, chairs, upholstered chairs, books etc. The most species identified included under common allergens: Aspergillus, Penicillium, and Mucor. There fungal species belonging to the genus identified in this study, can trigger serious diseases museum workers, such as for example Aspergillus fumigatus, known allergies and toxic effects that may occur. In some places of the museum, occupational exposure limit values to fungi present in the air in the work environment, recommended by the specialized literature, have been overcome.

  9. Standard methods for fungal brood disease research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this paper we describe the disease symptoms and protocols commonly used in research of honey bee fungal diseases chalkbrood and stonebrood, caused by Ascosphaera apis and Aspergillus spp. respectively....

  10. Scolecobasidium humicola, a fungal pathogen of fish

    USGS Publications Warehouse

    Ross, A.J.; Yasutake, W.T.

    1973-01-01

    Scolecobasidium humicola, a previously undescribed fungal pathogen of fish was isolated from coho salmon (Oncorhynchus kisutch). In natural infections the kidney was the organ most affected. The disease was difficult to transmit experimentally and appeared to be only weakly contagious.

  11. Foreword: Special issue on fungal grapevine diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An impressively large proportion of fungicides applied in European, North American and Australian agriculture has been used to manage grapevine powdery mildew (Erysiphe necator), grapevine downy mildew (Plasmopara viticola), and botrytis bunch rot (Botrytis cinerea). These fungal and oomycetous plan...

  12. Developing fungal pigments for "painting" vascular plants.

    PubMed

    Robinson, Sara C

    2012-02-01

    The use of fungal pigments as color additives to wood as a method to increase forest revenue is a relatively new, but quickly developing field. Sugar maple (Acer saccharum) is currently the primary utilized hardwood for spalting and appears to be the best suited North American hardwood for such purposes. The combination of Trametes versicolor and Bjerkandera adusta has been identified in several instances as a strong fungal pairing for zone line production; however, Xylaria polymorpha is capable of creating zone lines without the antagonism of a secondary fungus. Few fungal pigments have been developed for reliable use; Scytalidium cuboideum is capable of producing a penetrating pink/red stain, as well as a blue pigment after extended incubation, and Chlorociboria sp. produces a blue/green pigment if grown on aspen (Populus tremuloides). Several opportunities exist for stimulation of fungal pigments including the use of copper sulfate and changes in wood pH. PMID:22237673

  13. The structure and function of fungal cells

    NASA Technical Reports Server (NTRS)

    Nozawa, Y.

    1984-01-01

    The structure and function of fungal cell walls were studied with particular emphasis on dermatophytes. Extraction, isolation, analysis, and observation of the cell wall structure and function were performed. The structure is described microscopically and chemically.

  14. Acute Bronchitis

    MedlinePlus

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  15. CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans.

    PubMed

    Hall, Rebecca A; De Sordi, Luisa; Maccallum, Donna M; Topal, Hüsnü; Eaton, Rebecca; Bloor, James W; Robinson, Gary K; Levin, Lonny R; Buck, Jochen; Wang, Yue; Gow, Neil A R; Steegborn, Clemens; Mühlschlegel, Fritz A

    2010-01-01

    When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO(2) acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO(2)-mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO(2)/bicarbonate regulation of Cyr1p. Disruption of the CO(2)/bicarbonate receptor-site interferes selectively with C. albicans filamentation within fungal biomasses. Comparisons between the Drosophila melanogaster infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO(2) sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous Candida signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO(2)-signalling system. PMID:21124988

  16. Fungal biodegradation of pomegranate ellagitannins.

    PubMed

    Ascacio-Valdés, Juan A; Buenrostro, José J; De la Cruz, Reynaldo; Sepúlveda, Leonardo; Aguilera, Antonio F; Prado, Arely; Contreras, Juan C; Rodríguez, Raúl; Aguilar, Cristóbal N

    2014-01-01

    Ellagitannins (ETs) are phytochemicals derived from secondary metabolism associated to defense system, with complex chemical structures, which have high participation during all stages of protection against microbial infection. In this study, we report the fungal biodegradation of a bioactive ET, named punicaline which was recovered and purified from pomegranate peels and used as carbon source in solid-state culture (SSC) using polyurethane as solid support. SSC was kinetically monitored during 36 h of incubation time. ETs and glycosides consumption were spectrophotometrically determined. Ellagic acid (EA) accumulation was analyzed by HPLC. Several enzymatic activities were assayed (cellulase, xylanase, β-glucosydase, polyphenoloxidase, tannase, and ET hydrolyzing activities). The consumption levels of ETs and glycosides were 66 and 40%, while EA accumulation reached 42.02 mg g(-1). A differential pattern of enzymatic activities was found; evidence from our studies suggests that the ET hydrolyzing activity is directly associated to EA accumulation, and production of this enzyme may represent the most critical step to successfully develop a bioprocess for production of an important bioactive compound, the EA. PMID:23564673

  17. Biological roles of fungal carotenoids.

    PubMed

    Avalos, Javier; Carmen Limón, M

    2015-08-01

    Carotenoids are terpenoid pigments widespread in nature, produced by bacteria, fungi, algae and plants. They are also found in animals, which usually obtain them through the diet. Carotenoids in plants provide striking yellow, orange or red colors to fruits and flowers, and play important metabolic and physiological functions, especially relevant in photosynthesis. Their functions are less clear in non-photosynthetic microorganisms. Different fungi produce diverse carotenoids, but the mutants unable to produce them do not exhibit phenotypic alterations in the laboratory, apart of lack of pigmentation. This review summarizes the current knowledge on the functional basis for carotenoid production in fungi. Different lines of evidence support a protective role of carotenoids against oxidative stress and exposure to visible light or UV irradiation. In addition, the carotenoids are intermediary products in the biosynthesis of physiologically active apocarotenoids or derived compounds. This is the case of retinal, obtained from the symmetrical oxidative cleavage of β-carotene. Retinal is the light-absorbing prosthetic group of the rhodopsins, membrane-bound photoreceptors present also in many fungal species. In Mucorales, β-carotene is an intermediary in the synthesis of trisporoids, apocarotenoid derivatives that include the sexual hormones the trisporic acids, and they are also presumably used in the synthesis of sporopollenin polymers. In conclusion, fungi have adapted their ability to produce carotenoids for different non-essential functions, related with stress tolerance or with the synthesis of physiologically active by-products. PMID:25284291

  18. Atopic cough and fungal allergy

    PubMed Central

    Fujimura, Masaki; Ohkura, Noriyuki; Makimura, Koichi

    2014-01-01

    We have shown that some patients presenting with chronic bronchodilator-resistant non-productive cough have a global atopic tendency and cough hypersensitivity without nonspecific bronchial hyperresponsiveness, abbreviated as atopic cough (AC). The cough can be treated successfully with histamine H1 antagonists and/or glucocorticoids. Eosinophilic tracheobronchitis and cough hypersensitivity are pathological and physiological characteristics of AC. Fungus-associated chronic cough (FACC) is defined as chronic cough associated with basidiomycetous (BM) fungi found in induced sputum, and recognition of FACC has provided the possibility of using antifungal drugs as new treatment strategies. Bjerkandera adusta is a wood decay BM fungus, which has attracted attention because of its potential role in enhancing the severity of cough symptoms in FACC patients by sensitization to this fungus. Before making a diagnosis of “idiopathic cough” in cases of chronic refractory cough, remaining intractable cough-related laryngeal sensations, such as “a sensation of mucus in the throat (SMIT),” which is correlated with fungal colonization, should be evaluated and treated appropriately in each patient. The new findings, i.e., the detection of environmental mushroom spores that should not be present in the human airways in addition to the good clinical response of patients to antifungal drugs, may lead to the development of novel strategies for treatment of chronic cough. PMID:25383202

  19. Atopic cough and fungal allergy.

    PubMed

    Ogawa, Haruhiko; Fujimura, Masaki; Ohkura, Noriyuki; Makimura, Koichi

    2014-10-01

    We have shown that some patients presenting with chronic bronchodilator-resistant non-productive cough have a global atopic tendency and cough hypersensitivity without nonspecific bronchial hyperresponsiveness, abbreviated as atopic cough (AC). The cough can be treated successfully with histamine H1 antagonists and/or glucocorticoids. Eosinophilic tracheobronchitis and cough hypersensitivity are pathological and physiological characteristics of AC. Fungus-associated chronic cough (FACC) is defined as chronic cough associated with basidiomycetous (BM) fungi found in induced sputum, and recognition of FACC has provided the possibility of using antifungal drugs as new treatment strategies. Bjerkandera adusta is a wood decay BM fungus, which has attracted attention because of its potential role in enhancing the severity of cough symptoms in FACC patients by sensitization to this fungus. Before making a diagnosis of "idiopathic cough" in cases of chronic refractory cough, remaining intractable cough-related laryngeal sensations, such as "a sensation of mucus in the throat (SMIT)," which is correlated with fungal colonization, should be evaluated and treated appropriately in each patient. The new findings, i.e., the detection of environmental mushroom spores that should not be present in the human airways in addition to the good clinical response of patients to antifungal drugs, may lead to the development of novel strategies for treatment of chronic cough. PMID:25383202

  20. Fungal allelochemicals in insect pest management.

    PubMed

    Holighaus, Gerrit; Rohlfs, Marko

    2016-07-01

    Interactions between insects and fungi are widespread, and important mediators of these interactions are fungal chemicals that can therefore be considered as allelochemicals. Numerous studies suggest that fungal chemicals can affect insects in many different ways. Here, we apply the terminology established by insect-plant ecologists for categorizing the effect of fungal allelochemicals on insects and for evaluating the application potential of these chemicals in insect pest management. Our literature survey shows that fungal volatile and non-volatile chemicals have an enormous potential to influence insect behavior and fitness. Many of them still remain to be discovered, but some recent examples of repellents and toxins could open up new ways for developing safe insect control strategies. However, we also identified shortcomings in our understanding of the chemical ecology of insect-fungus interactions and the way they have been investigated. In particular, the mode-of-action of fungal allelochemicals has often not been appropriately designated or examined, and the way in which induction by insects affects fungal chemical diversity is poorly understood. This review should raise awareness that in-depth ecological studies of insect-fungus interactions can reveal novel allelochemicals of particular benefit for the development of innovative insect pest management strategies. PMID:27147531

  1. Natural occurrence of Zoophthora radicans (Entomophthorales: Entomophthoraceae) on Thaumastocoris peregrinus (Heteroptera: Thaumastocoridae), an invasive pest recently found in Brazil.

    PubMed

    Mascarin, Gabriel Moura; Duarte, Vanessa da Silveira; Brandão, Marcelo Mendes; Delalibera, Italo

    2012-07-01

    Occurrence of Zoophthora radicans infecting nymphs and adults of Thaumastocoris peregrinus Carpintero and Dellape, 2006 is reported in Brazil. This is a new record of host for this fungal species and the first fungal pathogen associated with this pest worldwide. Infection of Z. radicans on T. peregrinus populations on commercial Eucalyptus plantation (Eucalyptus spp.) reached up to 100%, and low insect densities were associated with high levels of fungal infection in three out of seven plots. This pathogen seems to be virulent against T. peregrinus and may play an important role in population regulations of this invasive pest through naturally induced epizootics. PMID:22490879

  2. [State of the art in invasive diseases by filamentous fungi].

    PubMed

    Pemán, Javier; Quindós, Guillermo

    2014-01-01

    Invasive fungal infections have become a major cause of morbimortality in intensive care patients, persons suffering from cancer or immune deficiencies, and other diseases with impaired immunity. Candida albicans remains the most frequent fungal pathogen, but advances in the diagnosis, prevention and treatment of invasive candidiasis are leading to important etiological changes. Among the emerging invasive mycoses, are those caused by filamentous fungi, such as Aspergillus, Lomentospora/Scedosporium, Fusarium or the Mucorales. Invasive aspergillosis is difficult to diagnose, and although there are diagnostic tools available, their use is not widespread, and their effectiveness vary depending on the group of patients. Clinical suspicion in high-risk patients, radiological diagnosis and the use of biomarkers, such as 1,3-β-D-glucan and galactomannan, can be of great help. However, diagnostic resources are limited in other mycoses, but radiology, pathological studies and the microbiological diagnosis can be useful. The high mortality of these mycoses requires early empirical antifungal treatment in many cases. Voriconazole is the first choice for treatment of the majority of aspergillosis, scedosporiasis, fusariosis and other hyalohyphomycoses. The treatment of mucormycoses, Lomentospora prolificans infections or mycoses by dematiaceous fungi are more complicated. Amphotericin B is active against many mucoralean fungi, but the combination of two or more antifungal agents could be a therapeutic alternative in many amphotericin B-refractory mycoses. Current clinical challenges include improving the diagnosis and the treatment of these mycoses, along with improving the adequate prevention in patients at high risk of suffering from them. PMID:25449676

  3. Fungal Mycotic Aneurysm of the Internal Carotid Artery Associated with Sphenoid Sinusitis in an Immunocompromised Patient: A Case Report and Review of the Literature.

    PubMed

    Azar, Marwan M; Assi, Roland; Patel, Natalie; Malinis, Maricar F

    2016-06-01

    In immunocompromised patients, invasive molds such as Aspergillus and Mucor can lead to locally aggressive angioinvasive infections that are often life-threatening. A particularly devastating complication is the development of a fungal mycotic aneurysm resulting from invasion of the arterial wall. Due to anatomic contiguity, the sphenoid sinus provides potential access for these fungi, which often colonize the respiratory sinuses, into the cavernous sinus and internal carotid artery (ICA), thus leading to the formation of ICA aneurysms. The ideal treatment of fungal ICA aneurysms includes a combination of surgical debridement and long-term effective antifungal therapy, but the role of endoscopic resection and the duration of antimicrobials are poorly defined. Here, we present the case of a 71-year-old immunocompromised patient who developed an ICA mycotic aneurysm, associated with a proven invasive fungal infection (presumptively Mucorales) of the sphenoid sinuses, as defined by EORTC/MSG criteria, and who survived after undergoing coil embolization with parent vessel sacrifice of the aneurysm in combination with liposomal amphotericin B. We also review the literature for published cases of invasive fungal sphenoid sinusitis associated with mycotic aneurysms of the ICA and provide a comparative analysis . PMID:26687073

  4. Acute incarcerated external abdominal hernia

    PubMed Central

    Yang, Xue-Fei

    2014-01-01

    External abdominal hernia occurs when abdominal organs or tissues leave their normal anatomic site and protrude outside the skin through the congenital or acquired weakness, defects or holes on the abdominal wall, including inguinal hernia, umbilical hernia, femoral hernia and so on. Acute incarcerated hernia is a common surgical emergency. With advances in minimally invasive devices and techniques, the diagnosis and treatment have witnessed major changes, such as the use of laparoscopic surgery in some cases to achieve minimally invasive treatment. However, strict adherence to the indications and contraindications is still required. PMID:25489584

  5. Proton Resonance Frequency Chemical Shift Thermometry: Experimental Design and Validation Towards High-Resolution Non-Invasive Temperature Monitoring, and in vivo Experience in a Non-human Primate Model of Acute Ischemic Stroke

    PubMed Central

    Mao, Hui; Howell, Leonard; Zhang, Xiaodong; Pate, K S; Magrath, P R; Tong, Frank; Wei, L; Qiu, D; Fleischer, C; Oshinski, J N

    2016-01-01

    BACKGROUND AND PURPOSE Applications for non-invasive biological temperature monitoring are widespread in biomedicine, and of particular interest in the context of brain temperature regulation, where traditionally costly and invasive monitoring schemes limit their applicability in many settings. Brain thermal regulation therefore remains controversial, motivating the development of non-invasive approaches such as temperature-sensitive NMR phenomena. The purpose of this work was to compare the utility of competing approaches to MR thermometry (MRT) employing proton resonance frequency chemical shift. Three methodologies were tested, hypothesizing the feasibility of a fast and accurate approach to chemical shift thermometry, in a phantom study at 3.0 Tesla. MATERIALS AND METHODS A conventional, paired approach (DIFF-1), an accelerated single-scan approach (DIFF-2), and a new, further accelerated strategy (DIFF-3) were tested. Phantom temperatures were modulated during real-time fiber optic temperature monitoring, with MRT derived simultaneously from temperature-sensitive changes in the water proton chemical shift (~0.01 ppm/°C). MRT was subsequently performed in a series of in vivo non-human primate experiments under physiologic and ischemic conditions testing its reproducibility and overall performance. RESULTS Chemical shift thermometry demonstrated excellent agreement with phantom temperatures for all three approaches (DIFF-1 linear regression R2=0.994, p<0.001, acquisition time 4 min 40 s; DIFF-2 R2=0.996, p<0.001, acquisition time 4 min; DIFF-3 R2=0.998, p<0.001, acquisition time 40 s). CONCLUSION These findings confirm the comparability in performance of three competing approaches MRT, and present in vivo applications under physiologic and ischemic conditions in a primate stroke model. PMID:25655874

  6. Richness and diversity of mammalian fungal communities shape innate and adaptive immunity in health and disease.

    PubMed

    Rizzetto, Lisa; De Filippo, Carlotta; Cavalieri, Duccio

    2014-11-01

    Human holobiomes are networks of mutualistic interactions between human cells and complex communities of bacteria and fungi that colonize the human body. The immune system must tolerate colonization with commensal bacteria and fungi but defend against invasion by either organism. Molecular ecological surveys of the human prokaryotic microbiota performed to date have revealed a remarkable degree of bacterial diversity and functionality. However, there is a dearth of information regarding the eukaryotic composition of the microbiota. In this review, we describe the ecology and the human niches of our fungal "fellow travelers" in both health and disease, discriminating between passengers, colonizers, and pathogens based on the interaction of these fungi with the human immune system. We conclude by highlighting the need to reconsider the etiology of many fungal and immune-related diseases in the context of the crosstalk between the human system and its resident microbial communities. PMID:25257052

  7. Identification and characterization of a novel family of selective antifungal compounds (CANBEFs) that interfere with fungal protein synthesis.

    PubMed

    Mircus, Gabriel; Albert, Nathaniel; Ben-Yaakov, Dafna; Chikvashvili, Dodo; Shadkchan, Yona; Kontoyiannis, Dimitrios P; Osherov, Nir

    2015-09-01

    Invasive mycotic infections have become more common during recent decades, posing an increasing threat to public health. However, despite the growing needs, treatments for invasive fungal infections remain unsatisfactory and are limited to a small number of antifungals. The aim of this study was to identify novel fungal cell wall inhibitors from a library of small chemical compounds using a conditional protein kinase C (PKC)-expressing strain of Aspergillus nidulans sensitive to cell wall-active agents. Eight "hit" compounds affecting cell wall integrity were identified from a screen of 35,000 small chemical compounds. Five shared a common basic molecular structure of 4-chloro-6-arylamino-7-nitro-benzofurazane (CANBEF). The most potent compound, CANBEF-24, was characterized further and was shown to inhibit the growth of pathogenic Aspergillus, Candida, Fusarium, and Rhizopus isolates at micromolar concentrations but not to affect the growth of mammalian cell lines. CANBEF-24 demonstrated strong synergy in combination with caspofungin, an antifungal that inhibits cell wall biosynthesis. Genetic and biochemical analyses with Aspergillus nidulans and Saccharomyces cerevisiae indicated that CANBEFs selectively inhibit fungal rRNA maturation and protein synthesis, suggesting that their effect on the cell wall is indirect. CANBEFs were nontoxic in insect (Galleria mellonella, Drosophila melanogaster) and mouse models of fungal infection. Preliminary evidence showing no therapeutic benefit in these models suggests that further cycles of optimization are needed for the development of this novel class of compounds for systemic use. PMID:26149982

  8. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections.

    PubMed

    Donnelley, Monica A; Zhu, Elizabeth S; Thompson, George R

    2016-01-01

    We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole's broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy. PMID:27330318

  9. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections

    PubMed Central

    Donnelley, Monica A; Zhu, Elizabeth S; Thompson, George R

    2016-01-01

    We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole’s broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy. PMID:27330318

  10. Etiological Analysis of Fungal Keratitis and Rapid Identification of Predominant Fungal Pathogens.

    PubMed

    He, Dan; Hao, Jilong; Gao, Song; Wan, Xue; Wang, Wanting; Shan, Qiushi; Wang, Li

    2016-02-01

    Fungal keratitis is a worldwide-distributed refractory and potentially blinding ocular infection caused by various fungi. It is necessary to investigate the etiological and epidemiological characteristics of this disease and establish a rapid and specific pathogenic identification method. Here, we isolated and identified fungal pathogens of 275 patients with presumed fungal keratitis from Jilin Province, China, and conducted statistical analyses of epidemiological information. The positive rate of fungal culture was 72.0 %. Fusarium sp. was the most common genus among 210 fungal isolates. The predominant species were Fusarium solani, Aspergillus fumigatus, and Candida glabrata, which accounted for over 50 % of the isolated organisms. Corneal trauma and previous use of drugs were the most important predisposing factors. In addition, a multiplex polymerase chain reaction (PCR) was designed with species-specific primers of the three species that could identify them with amplicons of approximately 330 bp from F. solani, 275 bp from A. fumigatus, and 230 bp from C. glabrata. Additionally, PCR with fungal universal primers and multiplex PCR were performed using DNA prepared by an improved DNA extraction method from corneal scrapings. With this method, fungal pathogens from corneal scrapings could be specifically and rapidly identified within 8 h. The culture-independent rapid identification of corneal scrapings may have great significance for the early diagnosis and treatment of fungal keratitis. PMID:26446032

  11. Protection by fungal starters against growth and secondary metabolite production of fungal spoilers of cheese.

    PubMed

    Nielsen, M S; Frisvad, J C; Nielsen, P V

    1998-06-30

    The influence of fungal starter cultures on growth and secondary metabolite production of fungal contaminants associated with cheese was studied on laboratory media and Camembert cheese. Isolates of the species Penicillium nalgiovense, P. camemberti, P. roqueforti and Geotrichum candidum were used as fungal starters. The species P. commune, P. caseifulvum, P. verrucosum, P. discolor, P. solitum, P. coprophilum and Aspergillus versicolor were selected as contaminants. The fungal starters showed different competitive ability on laboratory media and Camembert cheese. The presence of the Penicillium species, especially P. nalgiovense, showed an inhibitory effect on the growth of the fungal contaminants on laboratory media. G. candidum caused a significant inhibition of the fungal contaminants on Camembert cheese. The results indicate that G. candidum plays an important role in competition with undesirable microorganisms in mould fermented cheeses. Among the starters, P. nalgiovense caused the largest reduction in secondary metabolite production of the fungal contaminants on the laboratory medium. On Camembert cheese no significant changes in metabolite production of the fungal contaminants was observed in the presence of the starters. PMID:9706802

  12. Pathogenic roles for fungal melanins.

    PubMed

    Jacobson, E S

    2000-10-01

    Melanins represent virulence factors for several pathogenic fungi; the number of examples is growing. Thus, albino mutants of several genera (in one case, mutated precisely in the melanizing enzyme) exhibit decreased virulence in mice. We consider the phenomenon in relation to known chemical properties of melanin, beginning with biosynthesis from ortho-hydroquinone precursors which, when oxidized enzymatically to quinones, polymerize spontaneously to melanin. It follows that melanizing intermediates are cross-linking reagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appressorium) of certain plant pathogens. Polymeric melanins undergo reversible oxidation-reduction reactions between cell wall-penetrating quinone and hydroquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. The amount of buffering per cell approximately neutralizes the amount of oxidant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to trap unpaired electrons. We have suggested that the oxidation state of external melanin may be regulated by external Fe(II). An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H(2)O(2). Thus, problems in fungal pathogenesis have led to evolving hypotheses regarding melanin functioning. PMID:11023965

  13. Pathogenic Roles for Fungal Melanins

    PubMed Central

    Jacobson, Eric S.

    2000-01-01

    Melanins represent virulence factors for several pathogenic fungi; the number of examples is growing. Thus, albino mutants of several genera (in one case, mutated precisely in the melanizing enzyme) exhibit decreased virulence in mice. We consider the phenomenon in relation to known chemical properties of melanin, beginning with biosynthesis from ortho-hydroquinone precursors which, when oxidized enzymatically to quinones, polymerize spontaneously to melanin. It follows that melanizing intermediates are cross-linking reagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appressorium) of certain plant pathogens. Polymeric melanins undergo reversible oxidation-reduction reactions between cell wall-penetrating quinone and hydroquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. The amount of buffering per cell approximately neutralizes the amount of oxidant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to trap unpaired electrons. We have suggested that the oxidation state of external melanin may be regulated by external Fe(II). An independent hypothesis holds that in Cryptococcus neoformans, an important function of the melanizing enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), thereby forestalling generation of the harmful hydroxyl radical from H2O2. Thus, problems in fungal pathogenesis have led to evolving hypotheses regarding melanin functioning. PMID:11023965

  14. Ecotoxicity and fungal deterioration of recycled polypropylene/wood composites: effect of wood content and coupling.

    PubMed

    Sudár, András; López, María J; Keledi, Gergely; Vargas-García, M Carmen; Suárez-Estrella, Francisca; Moreno, Joaquín; Burgstaller, Christoph; Pukánszky, Béla

    2013-09-01

    Recycled polypropylene (rPP) was recovered from an industrial shredder and composites were prepared with a relatively wide range of wood content and with two coupling agents, a maleated PP (MAPP) and a maleated ethylene-propylene-diene elastomer (MAEPDM). The mechanical properties of the composites showed that the coupling agents change structure only slightly, but interfacial adhesion quite drastically. The durability of the materials was determined by exposing them to a range of fungi and, ecotoxicity was studied on the aquatic organism Vibrio fischeri. The composites generally exhibit low acute toxicity, with values below the levels considered to have direct ecotoxic effect on aquatic ecosystems (<2 toxic units). Their toxicity to V. fischeri depended on the presence of the coupling agents with larger E50 values in 24-h aqueous extracts from composites containing MAPP or MAEPDM in comparison to composites without any coupling agent. Evaluation of resistance against fungal colonization and deterioration proved that wood facilitates fungal colonization. Fungi caused slight mass loss (below 3%) but it was not correlated with substantial deterioration in material properties. MAPP seems to be beneficial in the retention of mechanical properties during fungal attack. rPP/wood composites can be considered non-ecotoxic and quite durable, but the influence of wood content on resistance to fungal attack must be taken into account for materials intended for applications requiring long-term outdoor exposure. PMID:23769467

  15. The Evolution of Fungal Metabolic Pathways

    PubMed Central

    Rokas, Antonis

    2014-01-01

    Fungi contain a remarkable range of metabolic pathways, sometimes encoded by gene clusters, enabling them to digest most organic matter and synthesize an array of potent small molecules. Although metabolism is fundamental to the fungal lifestyle, we still know little about how major evolutionary processes, such as gene duplication (GD) and horizontal gene transfer (HGT), have interacted with clustered and non-clustered fungal metabolic pathways to give rise to this metabolic versatility. We examined the synteny and evolutionary history of 247,202 fungal genes encoding enzymes that catalyze 875 distinct metabolic reactions from 130 pathways in 208 diverse genomes. We found that gene clustering varied greatly with respect to metabolic category and lineage; for example, clustered genes in Saccharomycotina yeasts were overrepresented in nucleotide metabolism, whereas clustered genes in Pezizomycotina were more common in lipid and amino acid metabolism. The effects of both GD and HGT were more pronounced in clustered genes than in their non-clustered counterparts and were differentially distributed across fungal lineages; specifically, GD, which was an order of magnitude more abundant than HGT, was most frequently observed in Agaricomycetes, whereas HGT was much more prevalent in Pezizomycotina. The effect of HGT in some Pezizomycotina was particularly strong; for example, we identified 111 HGT events associated with the 15 Aspergillus genomes, which sharply contrasts with the 60 HGT events detected for the 48 genomes from the entire Saccharomycotina subphylum. Finally, the impact of GD within a metabolic category was typically consistent across all fungal lineages, whereas the impact of HGT was variable. These results indicate that GD is the dominant process underlying fungal metabolic diversity, whereas HGT is episodic and acts in a category- or lineage-specific manner. Both processes have a greater impact on clustered genes, suggesting that metabolic gene clusters

  16. Divergent and Convergent Evolution of Fungal Pathogenicity

    PubMed Central

    Shang, Yanfang; Xiao, Guohua; Zheng, Peng; Cen, Kai; Zhan, Shuai; Wang, Chengshu

    2016-01-01

    Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen–host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus–animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation. PMID:27071652

  17. Divergent and Convergent Evolution of Fungal Pathogenicity.

    PubMed

    Shang, Yanfang; Xiao, Guohua; Zheng, Peng; Cen, Kai; Zhan, Shuai; Wang, Chengshu

    2016-01-01

    Fungal pathogens of plants and animals have multifarious effects; they cause devastating damages to agricultures, lead to life-threatening diseases in humans, or induce beneficial effects by reducing insect pest populations. Many virulence factors have been determined in different fungal pathogens; however, the molecular determinants contributing to fungal host selection and adaptation are largely unknown. In this study, we sequenced the genomes of seven ascomycete insect pathogens and performed the genome-wide analyses of 33 species of filamentous ascomycete pathogenic fungi that infect insects (12 species), plants (12), and humans (9). Our results revealed that the genomes of plant pathogens encode more proteins and protein families than the insect and human pathogens. Unexpectedly, more common orthologous protein groups are shared between the insect and plant pathogens than between the two animal group pathogens. We also found that the pathogenicity of host-adapted fungi evolved multiple times, and that both divergent and convergent evolutions occurred during pathogen-host cospeciation thus resulting in protein families with similar features in each fungal group. However, the role of phylogenetic relatedness on the evolution of protein families and therefore pathotype formation could not be ruled out due to the effect of common ancestry. The evolutionary correlation analyses led to the identification of different protein families that correlated with alternate pathotypes. Particularly, the effector-like proteins identified in plant and animal pathogens were strongly linked to fungal host adaptation, suggesting the existence of similar gene-for-gene relationships in fungus-animal interactions that has not been established before. These results well advance our understanding of the evolution of fungal pathogenicity and the factors that contribute to fungal pathotype formation. PMID:27071652

  18. Degradation of fungal DNA in formalin-fixed paraffin-embedded sinus fungal balls hampers reliable sequence-based identification of fungi.

    PubMed

    Cabaret, Odile; Toussain, Guillaume; Abermil, Nassera; Alsamad, Issam Abd; Botterel, Françoise; Costa, Jean-Marc; Papon, Jean-François; Bretagne, Stéphane

    2011-04-01

    Identification of the etiologic agent responsible for sinus fungal ball (SFB) is rarely obtained due to either the culture of patient specimens not being ordered or if cultures were inoculated they proved to be negative. Obviously, this has a significant impact on the design of appropriate therapeutic strategies. We investigated whether paraffin-embedded (PE) tissues, the only materials often available, were suitable for the correct identification of the responsible fungi. We obtained PE tissues of SFB from 16 different patients who had risk factors for invasive fungal infections. DNA was extracted using an automated extractor and the internal transcribed spacer (ITS) sequenced following amplification with two sets of primers designed to amplify >300 bp fragments. This was attempted in parallel with a real-time quantitative PCR assay targeting Aspergillus spp. mitochondrial DNA designed to amplify <150 bp fragments. ITS sequencing succeeded in appropriately identifying the etiologic agents in 10 of the 16 samples (nine Aspergillus fumigatus, one Lewia spp.). In contrast, the <150 bp PCR assay amplified all specimens correctly except the one involving Lewia spp. If fungal identification is warranted to understand the pathophysiology of SFB and guide clinicians, we cannot rely only on ITS sequencing of the DNA obtained from PE tissues. The main reason is probably due to the fact that formalin prevents amplification of long DNA fragments and consequently, frozen or fresh tissues should be employed. PMID:20950222

  19. Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

    PubMed Central

    Hsu, Joe L.; Khan, Mohammad A.; Sobel, Raymond A.; Jiang, Xinguo; Clemons, Karl V.; Nguyen, Tom T.; Stevens, David A.; Martinez, Marife; Nicolls, Mark R.

    2013-01-01

    Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections. PMID:24155924

  20. 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. PMID:26931647

  1. Biochemical basis of heterogeneity in acute presentations of propionic acidemia.

    PubMed

    Sindgikar, Seema Pavaman; Rao, Suchetha; Shenoy, Rathika D; Kamath, Nutan

    2013-01-01

    Propionic acidemia (PA), an uncommon organic acidemia has varied clinical and metabolic presentation causing difficulty and delay in the diagnosis. We report a case of PA in an infant who presented with failure to thrive, acute encephalopathy due to severe hyperammonemia without acidosis and fungal sepsis. The biochemical basis of severe hyperammonemia is discussed. PMID:24381430

  2. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition. PMID:26520203

  3. [Allergic fungal sinusitis: is this rare disease an allergy or infection?].

    PubMed

    Berrettini, S; Carabelli, A; Papini, M; Ciancia, E; Sellari Franceschini, S

    1996-10-01

    Allergic Fungal Sinusitis (AFS) is a newly recognized form of benign, non invasive sinusitis the histopathologic features of which are similar to those of allergic bronchopulmonary aspergillosis. AFS is a rare condition. However, because treatment and prognosis vary widely, it is important that this disorder be recognized and differentiated from chronic bacterial sinusitis and other forms of fungal sinusitis. AFS does not discriminate by age although it is primarily found in young adults. AFS patients are usually atopic, often having a history of asthma and nasal polyposis. Many have suffered from the symptoms of chronic sinusitis for years while others have had multiple sinus surgery. Radiographs reveal the involvement of multiple sinuses, often with bone destruction. Laboratory findings support an allergic state with a marked increase in eosinophilia and total IgE. At times RAST testing proves positive for fungi and immediate cutaneous reactivity to fungi is also present. Histologic review of the sinus contents reveals characteristic "allergic mucin", with numerous eosinophiles, Charcot-Leyden crystals and fungal hyphae, without any fungi tissue invasion. A wide variety of fungal agents has been implicated, although the majority belong the Dematiacee family. Those patients with allergic mucin but no documented fungi are indicated as having AFS-like syndrome. The pathogenesis of AFS is uncertain. There is controversy in the literature as to what role hypersensitivity (Gell and Coombs type I and type III responses) in infection play. To date current therapeutic recommendations include complete exenteration of all allergic mucin. Adjunctive, short-term systemic steroids often prove useful and nasal steroid spray should be continued for long term. Systemic antifungal agents are not recommended in AFS. Recurrence is common and thus close clinical, endoscopic and radiographic follow-up is important. The clinicopathologic features of one patient with AFS are reported

  4. Infectious complications in children with acute myeloid leukemia: decreased mortality in multicenter trial AML-BFM 2004

    PubMed Central

    Bochennek, K; Hassler, A; Perner, C; Gilfert, J; Schöning, S; Klingebiel, T; Reinhardt, D; Creutzig, U; Lehrnbecher, T

    2016-01-01

    Infections are an important cause for morbidity and mortality in pediatric acute myeloid leukemia (AML). We therefore characterized infectious complications in children treated according to the trial AML-BFM 2004. Patients with Down syndrome were excluded from the analysis. Data were gathered from the medical records in the hospital where the patients were treated. A total of 405 patients (203 girls; median age 8.4 years) experienced 1326 infections. Fever without identifiable source occurred in 56.1% of the patients and clinically and microbiologically documented infections in 17.5% and 32.4% of the patients, respectively. In all, 240 Gram-positive (112 viridans group streptococci) and 90 Gram-negative isolates were recovered from the bloodstream. Invasive fungal infection was diagnosed in 3% of the patients. Three children each died of Gram-negative bacteremia and invasive aspergillosis, respectively. As compared with the results of AML-BFM 93 with lower dose intensity, infection-related morbidity was slightly higher in AML-BFM 2004 (3.3. versus 2.8 infections per patient), whereas infection-related mortality significantly decreased (1.5% versus 5.4% P=0.003). Specific anti-infective recommendations included in the treatment protocol, regular training courses for pediatric hematologists and increasing experience may be the reason for reduced infection-related mortality in children with AML. Further studies are needed to decrease infection-related morbidity. PMID:26771808

  5. Fueling the Future with Fungal Genomes

    SciTech Connect

    Grigoriev, Igor V.

    2014-10-27

    Genomes of fungi relevant to energy and environment are in focus of the JGI Fungal Genomic Program. One of its projects, the Genomics Encyclopedia of Fungi, targets fungi related to plant health (symbionts and pathogens) and biorefinery processes (cellulose degradation and sugar fermentation) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Science Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for users to nominate new species for sequencing. Over 400 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 will lead 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.

  6. Proteomics of survival structures of fungal pathogens.

    PubMed

    Loginov, Dmitry; Šebela, Marek

    2016-09-25

    Fungal pathogens are causal agents of numerous human, animal, and plant diseases. They employ various infection modes to overcome host defense systems. Infection mechanisms of different fungi have been subjected to many comprehensive studies. These investigations have been facilitated by the development of various '-omics' techniques, and proteomics has one of the leading roles in this regard. Fungal conidia and sclerotia could be considered the most important structures for pathogenesis as their germination is one of the first steps towards a host infection. They represent interesting objects for proteomic studies because of the presence of unique proteins with unexplored biotechnological potential required for pathogen viability, development and the subsequent host infection. Proteomic peculiarities of survival structures of different fungi, including those of biotechnological significance (e.g., Asperillus fumigatus, A. nidulans, Metarhizium anisopliae), in a dormant state, as well as changes in the protein production during early stages of fungal development are the subjects of the present review. We focused on biological aspects of proteomic studies of fungal survival structures rather than on an evaluation of proteomic approaches. For that reason, proteins that have been identified in this context are discussed from the point of view of their involvement in different biological processes and possible functions assigned to them. This is the first review paper summarizing recent advances in proteomics of fungal survival structures. PMID:26777984

  7. Incidence and Outcome of Documented Fungal Endocarditis

    PubMed Central

    Badiee, Parisa; Amirghofran, Ahmad Ali; Ghazi Nour, Mohammad; Shafa, Masih; Nemati, Mohammad Hassan

    2014-01-01

    Background: Fungal endocarditis, the most severe form of infective endocarditis, is characterized by excessive mortality and morbidity. Objectives: The present study aimed to analyze the characteristics of fungal endocarditis to improve the management of these patients. Materials and Methods: In this cross-sectional study, vegetations on the mitral or tricuspid valves and embolic material surgically removed from the patients with suspected infective endocarditis between December 2009 and November 2011 were examined for fungal infection by direct smear and culture, and the susceptibility patterns of the isolated species were determined. Then, blood samples were cultured on BACTEC media and real-time PCR was done with blood and tissue samples. Results: Of the 31 patients with suspected infective endocarditis who did not respond to antibacterial therapy, 11 had confirmed fungal endocarditis. The most frequent predisposing risk factors were previous surgery and drug abuse. The organisms isolated were Aspergillus spp. and Candida albicans. Resistance to amphotericin B and itraconazole was observed in Aspergillus species, and to fluconazole in Candida albicans. Positive PCR results were obtained in blood and tissue samples. Conclusions: Fungal endocarditis should be considered in the patients not responsive to antimicrobials. Moreover, management of these patients can be improved with molecular diagnostic methods and by determining the susceptibility patterns of the etiologic agents. PMID:25614858

  8. [Pulmonary fungal infection in patients with AIDS].

    PubMed

    Denis, B; Lortholary, O

    2013-10-01

    Fungal infections are the most common opportunistic infections (OI) occurring during the course of HIV infection, though their incidence has decreased dramatically with the introduction of highly active antiretroviral therapy (cART). Most cases occur in untreated patients, noncompliant patients or patients whose multiple antiretroviral regimens have failed and they are a good marker of the severity of cellular immunodepression. Pneumocystis jiroveci pneumonia is the second most frequent OI in France and cryptococcosis remains a major problem in the Southern Hemisphere. With the increase in travel, imported endemic fungal infection can occur and may mimic other infections, notably tuberculosis. Fungal infections often have a pulmonary presentation but an exhaustive search for dissemination should be made in patients infected with HIV, at least those at an advanced stage of immune deficiency. Introduction of cART in combination with anti-fungal treatment depends on the risk of AIDS progression and on the risk of cumulative toxicity and the immune reconstitution inflammatory syndrome (IRIS) if introduced too early. Fungal infections in HIV infected patients remain a problem in the cART era. IRIS can complicate the management and requires an optimised treatment regime. PMID:24182654

  9. Towards a Cancer Drug of Fungal Origin

    PubMed Central

    Kornienko, Alexander; Evidente, Antonio; Vurro, Maurizio; Mathieu, Véronique; Cimmino, Alessio; Evidente, Marco; van Otterlo, Willem A. L.; Dasari, Ramesh; Lefranc, Florence; Kiss, Robert

    2015-01-01

    Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi-derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed and potential solutions that could be pursued by researchers are highlighted. PMID:25850821

  10. Fungal Genomics for Energy and Environment

    SciTech Connect

    Grigoriev, Igor V.

    2013-03-11

    Genomes of fungi relevant to energy and environment are in focus of the Fungal Genomic Program at the US Department of Energy Joint Genome Institute (JGI). One of its projects, 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) by means of genome sequencing and analysis. New chapters of the Encyclopedia can be opened with user proposals to the JGI Community Sequencing Program (CSP). Another JGI project, the 1000 fungal genomes, explores fungal diversity on genome level at scale and is open for users to nominate new species for sequencing. Over 200 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.

  11. Fungal endophytes: modifiers of plant disease.

    PubMed

    Busby, Posy E; Ridout, Mary; Newcombe, George

    2016-04-01

    Many recent studies have demonstrated that non-pathogenic fungi within plant microbiomes, i.e., endophytes ("endo" = within, "phyte" = plant), can significantly modify the expression of host plant disease. The rapid pace of advancement in endophyte ecology warrants a pause to synthesize our understanding of endophyte disease modification and to discuss future research directions. We reviewed recent literature on fungal endophyte disease modification, and here report on several emergent themes: (1) Fungal endophyte effects on plant disease span the full spectrum from pathogen antagonism to pathogen facilitation, with pathogen antagonism most commonly reported. (2) Agricultural plant pathosystems are the focus of research on endophyte disease modification. (3) A taxonomically diverse group of fungal endophytes can influence plant disease severity. And (4) Fungal endophyte effects on plant disease severity are context-dependent. Our review highlights the importance of fungal endophytes for plant disease across a broad range of plant pathosystems, yet simultaneously reveals that complexity within plant microbiomes presents a significant challenge to disentangling the biotic environmental factors affecting plant disease severity. Manipulative studies integrating eco-evolutionary approaches with emerging molecular tools will be poised to elucidate the functional importance of endophytes in natural plant pathosystems that are fundamental to biodiversity and conservation. PMID:26646287

  12. Mycorrhizal co-invasion and novel interactions depend on neighborhood context.

    PubMed

    Moeller, Holly V; Dickie, Ian A; Peltzer, Duane A; Fukami, Tadashi

    2015-09-01

    Biological invasions are a rapidly increasing driver of global change, yet fundamental gaps remain in our understanding of the factors determining the success or extent of invasions. For example, although most woody plant species depend on belowground mutualists such as mycorrhizal fungi and nitrogen-fixing bacteria, the relative importance of these mutualisms in conferring invasion success is unresolved. Here, we describe how neighborhood context (identity of nearby tree species) affects the formation of belowground ectomycorrhizal partnerships between fungi and seedlings of a widespread invasive tree species, Pseudotsuga menziesii (Douglas-fir), in New Zealand. We found that the formation of mycorrhizal partnerships, the composition of the fungal species involved in these partnerships, and the origin of the fungi (co-invading or native to New Zealand) all depend on neighborhood context. Our data suggest that nearby ectomycorrhizal host trees act as both a reservoir of fungal inoculum and a carbon source for late-successional and native fungi. By facilitating mycorrhization of P. menziesii seedlings, adult trees may alleviate mycorrhizal limitation at the P. menziesii invasion front. These results highlight the importance of studying biological invasions across multiple ecological settings to understand establishment success and invasion speed. PMID:26594692

  13. Diversity of fungal endophytes in non-native Phragmites australis in the Great Lakes

    USGS Publications Warehouse

    Clay, Keith; Shearin, Zachery; Bourke, Kimberly; Bickford, Wesley A.; Kowalski, Kurt P.

    2016-01-01

    Plant–microbial interactions may play a key role in plant invasions. One common microbial interaction takes place between plants and fungal endophytes when fungi asymptomatically colonize host plant tissues. The objectives of this study were to isolate and sequence fungal endophytes colonizing non-native Phragmites australis in the Great Lakes region to evaluate variation in endophyte community composition among three host tissue types and three geographical regions. We collected entire ramets from multiple clones and populations, surface sterilized plant tissues, and plated replicate tissue samples from leaves, stems, and rhizomes on corn meal agar plates to culture and isolate fungal endophytes. Isolates were then subjected to Sanger sequencing of the ITS region of the nuclear ribosomal DNA. Sequences were compared to fungal databases to define operational taxonomic units (OTUs) that were analyzed statistically for community composition. In total, we obtained 173 endophyte isolates corresponding to 55 OTUs, 39 of which were isolated only a single time. The most common OTU corresponded most closely to Sarocladium strictum and comprised 25 % of all fungal isolates. More OTUs were found in stem tissues, but endophyte diversity was greatest in rhizome tissues. PERMANOVA analyses indicated significant differences in endophyte communities among tissue types, geographical regions, and the interaction between those factors, but no differences among individual ramets were detected. The functional role of the isolated endophytes is not yet known, but one genus isolated here (Stagonospora) has been reported to enhance Phragmites growth. Understanding the diversity and functions of Phragmites endophytes may provide targets for control measures based on disrupting host plant/endophyte interactions.

  14. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  15. Chronic fungal sinusitis leading to disastrous cerebral aspergillosis: a case report

    PubMed Central

    2009-01-01

    Cerebral angioinvasion is a fatal complication of disseminated aspergillosis and has been rarely described in diabetic population in the absence of ketoacidosis. We present a case of invasive fungal sinusitis in a 79 year old diabetic man who presented with chronic frontal headaches. Despite appropriate medical and surgical treatment, the disease progressed and the patient eventually succumbed to a fatal ruptured mycotic aneurysm. We emphasize that clinicians should consider this in the differential diagnoses of all diabetics who present with chronic sinusitis, as early diagnosis could be the key in the successful treatment. PMID:20069073

  16. Acute myocarditis presenting as cardiac tamponade.

    PubMed Central

    Nwizu, Chidi; Onwuanyi, Anekwe E.

    2004-01-01

    We report a case of acute fulminant myocarditis presenting with cardiac tamponade and shock. The patient was managed in the coronary care unit with emergency pericardiotomy, invasive hemodynamic monitoring, and supportive therapy for cardiac failure. Pleural effusion and pneumonia complicated her clinical course. She responded well to therapy with normalization of left ventricular systolic function. This case demonstrates the potential for complete recovery with appropriate management in acute myocarditis even with a fulminant course. Images Figure 1 PMID:15586655

  17. Fungal infections in burns: a comprehensive review.

    PubMed

    Struck, M F; Gille, J

    2013-09-30

    Burn wound infections remain the most important factor limiting survival in burn intensive care units. Large wound surface, impaired immune systems, and broad-spectrum antibiotic therapy contribute to the growth of opportunistic fungal species. Faced with challenging fluid resuscitation, wound excision and cardiopulmonary stabilization, mycosis in burns are likely to be underestimated. Diagnostic performance can sometimes be delayed because clinical signs are unspecific and differentiation between colonization and infection is difficult. Therapeutic measures range from infection prophylaxis over treatment with antifungal agents towards radical amputation of infected limbs. New methods of early and reliable detection of fungal organisms, as well as the use of novel antifungal substances, are promising but require wider establishment to confirm the beneficial effects in burn patients. This review aims to highlight the main important aspects of fungal infections in burns including incidence, infection control, diagnostic and therapeutic approaches, prognosis and outcomes. PMID:24563641

  18. Virulence factors in fungal pathogens of man.

    PubMed

    Brunke, Sascha; Mogavero, Selene; Kasper, Lydia; Hube, Bernhard

    2016-08-01

    Human fungal pathogens are a commonly underestimated cause of severe diseases associated with high morbidity and mortality. Like other pathogens, their survival and growth in the host, as well as subsequent host damage, is thought to be mediated by virulence factors which set them apart from harmless microbes. In this review, we describe and discuss commonly employed strategies for fungal survival and growth in the host and how these affect the host-fungus interactions to lead to disease. While many of these strategies require host-specific virulence factors, more generally any fitness factor which allows growth under host-like conditions can be required for pathogenesis. Furthermore, we briefly summarize how different fungal pathogens are thought to damage the host. We find that in addition to a core of common activities relevant for growth, different groups of fungi employ different strategies which in spite of (or together with) the host's response can lead to disease. PMID:27257746

  19. Prospects for the development of fungal vaccines.

    PubMed Central

    Deepe, G S

    1997-01-01

    In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require recognition and aggressive management. The escalation in the incidence and prevalence of infection has prompted a renewed interest in vaccine development. Herein, I discuss the most recent developments in the search for vaccines to combat fungal infections. Investigators have discovered several inert substances from various fungi that can mediate protection in animal models. The next challenge will be to find the suitable mode of delivery for these immunogens. PMID:9336663

  20. [Fungal keratitis caused by Cylindrocarpon lichenicola].

    PubMed

    Gaujoux, T; Borsali, E; Gavrilov, J-C; Touzeau, O; Goldschmidt, P; Despiau, M-C; Chaumeil, C; Laroche, L; Borderie, V

    2012-05-01

    We report a case of a 67-year-old woman with no significant past ocular history, who was referred for management of an unresponsive microbial keratitis resulting from trauma with a piece of clothing fabric 1 month previously in Portugal and worsening despite topical fortified antibiotics. On examination, visual acuity was limited to "light perception". Slit lamp examination revealed an 11×11mm full-thickness corneal infiltrate. Confocal images showed branching hyphae suggestive of a fungal infection. Fungal cultures of corneal scrapings revealed growth of Cylindrocarpon lichenicola, a saprophytic, filamentous fungus, which is an unusual cause of keratitis. Despite aggressive antifungal therapy with voriconazole and amphotericin B, she required penetrating keratoplasty for impending corneal perforation. Follow-up was uneventful, with no recurrence at 1 year. Fungal infections must be suspected in all corneal ulcers of traumatic etiology. Specific cultures and confocal microscopy must be performed early, so as to enable early treatment modification. PMID:22137679

  1. Fungal infections in burns: a comprehensive review

    PubMed Central

    Struck, M.F.; Gille, J.

    2013-01-01

    Summary Burn wound infections remain the most important factor limiting survival in burn intensive care units. Large wound surface, impaired immune systems, and broad-spectrum antibiotic therapy contribute to the growth of opportunistic fungal species. Faced with challenging fluid resuscitation, wound excision and cardiopulmonary stabilization, mycosis in burns are likely to be underestimated. Diagnostic performance can sometimes be delayed because clinical signs are unspecific and differentiation between colonization and infection is difficult. Therapeutic measures range from infection prophylaxis over treatment with antifungal agents towards radical amputation of infected limbs. New methods of early and reliable detection of fungal organisms, as well as the use of novel antifungal substances, are promising but require wider establishment to confirm the beneficial effects in burn patients. This review aims to highlight the main important aspects of fungal infections in burns including incidence, infection control, diagnostic and therapeutic approaches, prognosis and outcomes. PMID:24563641

  2. Invasive aspergillosis presenting as swelling of the buccal mucosa in an immunocompetent individual.

    PubMed

    Ganesh, Praveen; Nagarjuna, Muralidhara; Shetty, Samarth; Kumar, Pradeep; Bhat, Venkatraman; Salins, Paul C

    2015-02-01

    Fungi are ubiquitous in nature but have low virulence and cause disease usually when the host defenses are compromised. Fungal infections of the central nervous system are rare and are usually seen in immunocompromised patients. However, in recent years, there has been an increase in the number of central nervous system fungal infections in immunocompetent individuals. Intracranial fungal granulomas are rare space-occupying lesions. Among these, Aspergillus granuloma is the most common. Craniocerebral involvement by aspergillosis usually occurs via the hematogenous route or through contiguous spread from the paranasal sinuses. Predominant symptoms associated with cranial fungal granuloma include headache, vomiting, proptosis, and visual disturbances. Common signs include papilledema, cranial neuropathy, hemiparesis, and meningismus. We present a case of invasive Aspergillus granuloma in an immunocompetent individual, who presented with a palpable mass in the buccal mucosa following removal of an impacted mandibular third molar but with no other characteristic signs and symptoms of invasive fungal granuloma. To our knowledge, there is no documentation of aspergillosis presenting as a swelling in the buccal mucosa. Unexplained swellings in the buccal mucosa should be viewed with a high degree of suspicion and investigated thoroughly at the earliest. PMID:25487984

  3. Identification & Characterization of Fungal Ice Nucleation Proteins

    NASA Astrophysics Data System (ADS)

    Scheel, Jan Frederik; Kunert, Anna Theresa; Kampf, Christopher Johannes; Mauri, Sergio; Weidner, Tobias; Pöschl, Ulrich; Fröhlich-Nowoisky, Janine

    2016-04-01

    Freezing of water at relatively warm subfreezing temperatures is dependent on ice nucleation catalysis facilitated by ice nuclei (IN). These IN can be of various origins and although extensive research was done and progress was achieved, the nature and mechanisms leading to an effective IN are to date still poorly understood. Some of the most important processes of our geosphere like the water cycle are highly dependent on effective ice nucleation at temperatures between -2°C - -8°C, a temperature range which is almost exclusively covered by biological IN (BioIN). BioIN are usually macromolecular structures of biological polymers. Sugars as well as proteins have been reported to serve as IN and the best characterized BioIN are ice nucleation proteins (IN-P) from gram negative bacteria. Fungal strains from Fusarium spp. were described to be effective IN at subfreezing temperatures up to -2°C already 25 years ago and more and more fungal species are described to serve as efficient IN. Fungal IN are also thought to be proteins or at least contain a proteinaceous compound, but to date the fungal IN-P primary structure as well as their coding genetic elements of all IN active fungi are unknown. The aim of this study is a.) to identify the proteins and their coding genetic elements from IN active fungi (F. acuminatum, F. avenaceum, M. alpina) and b.) to characterize the mechanisms by which fungal IN serve as effective IN. We designed an interdisciplinary approach using biological, analytical and physical methods to identify fungal IN-P and describe their biological, chemical, and physical properties.

  4. Fractal dimension based corneal fungal infection diagnosis

    NASA Astrophysics Data System (ADS)

    Balasubramanian, Madhusudhanan; Perkins, A. Louise; Beuerman, Roger W.; Iyengar, S. Sitharama

    2006-08-01

    We present a fractal measure based pattern classification algorithm for automatic feature extraction and identification of fungus associated with an infection of the cornea of the eye. A white-light confocal microscope image of suspected fungus exhibited locally linear and branching structures. The pixel intensity variation across the width of a fungal element was gaussian. Linear features were extracted using a set of 2D directional matched gaussian-filters. Portions of fungus profiles that were not in the same focal plane appeared relatively blurred. We use gaussian filters of standard deviation slightly larger than the width of a fungus to reduce discontinuities. Cell nuclei of cornea and nerves also exhibited locally linear structure. Cell nuclei were excluded by their relatively shorter lengths. Nerves in the cornea exhibited less branching compared with the fungus. Fractal dimensions of the locally linear features were computed using a box-counting method. A set of corneal images with fungal infection was used to generate class-conditional fractal measure distributions of fungus and nerves. The a priori class-conditional densities were built using an adaptive-mixtures method to reflect the true nature of the feature distributions and improve the classification accuracy. A maximum-likelihood classifier was used to classify the linear features extracted from test corneal images as 'normal' or 'with fungal infiltrates', using the a priori fractal measure distributions. We demonstrate the algorithm on the corneal images with culture-positive fungal infiltrates. The algorithm is fully automatic and will help diagnose fungal keratitis by generating a diagnostic mask of locations of the fungal infiltrates.

  5. Fungal infections in burns: Diagnosis and management

    PubMed Central

    Capoor, Malini R.; Sarabahi, Sujata; Tiwari, Vinay Kumar; Narayanan, Ravi Prakash

    2010-01-01

    Burn wound infection (BWI) is a major public health problem and the most devastating form of trauma worldwide. Fungi cause BWI as part of monomicrobial or polymicrobial infection, fungaemia, rare aggressive soft tissue infection and as opportunistic infections. The risk factors for acquiring fungal infection in burns include age of burns, total burn size, body surface area (BSA) (30–60%), full thickness burns, inhalational injury, prolonged hospital stay, late surgical excision, open dressing, artificial dermis, central venous catheters, antibiotics, steroid treatment, long-term artificial ventilation, fungal wound colonisation (FWC), hyperglycaemic episodes and other immunosuppressive disorders. Most of the fungal infections are missed owing to lack of clinical awareness and similar presentation as bacterial infection coupled with paucity of mycology laboratories. Expedient diagnosis and treatment of these mycoses can be life-saving as the mortality is otherwise very high. Emergence of resistance in non-albicans Candida spp., unusual yeasts and moulds in fungal BWI, leaves very few fungi susceptible to antifungal drugs, leaving many patients susceptible. There is a need to speciate fungi as far as the topical and systemic antifungal is concerned. Deep tissue biopsy and other relevant samples are processed by standard mycological procedures using direct microscopy, culture and histopathological examination. Patients with FWC should be treated by aggressive surgical debridement and, in the case of fungal wound infection (FWI), in addition to surgical debridement, an intravenous antifungal drug, most commonly amphotericin B or caspofungin, is prescribed followed by de-escalating with voriconazole or itraconazole, or fluconazole depending upon the species or antifungal susceptibility, if available. The propensity for fungal infection increases, the longer the wound is present. Therefore, the development of products to close the wound more rapidly, improvement in

  6. Vesicular transport across the fungal cell wall

    PubMed Central

    Casadevall, Arturo; Nosanchuk, Joshua D.; Williamson, Peter; Rodrigues, Marcio L.

    2014-01-01

    Recent findings indicate that fungi use vesicular transport to deliver substances across their cell walls. Fungal vesicles are similar to mammalian exosomes and could originate from cytoplasmic multivesicular bodies. Vesicular transport enables the export of large molecules across the cell wall, and vesicles contain lipids, proteins and polysaccharides, many of which are associated with virulence. Concentration of fungal products in vesicles could increase their efficiency in food acquisition and/or delivering potentially noxious substances to other cells, such as amoebae or phagocytes. The discovery of vesicular transport in fungi opens many new avenues for investigation in basic cell biology and pathogenesis. PMID:19299133

  7. Fungal proteinaceous compounds with multiple biological activities.

    PubMed

    Ng, Tzi Bun; Cheung, Randy Chi Fai; Wong, Jack Ho; Chan, Yau Sang; Dan, Xiuli; Pan, Wenliang; Wang, Hexiang; Guan, Suzhen; Chan, Ki; Ye, Xiuyun; Liu, Fang; Xia, Lixin; Chan, Wai Yee

    2016-08-01

    Fungi comprise organisms like molds, yeasts and mushrooms. They have been used as food or medicine for a long time. A large number of fungal proteins or peptides with diverse biological activities are considered as antibacterial, antifungal, antiviral and anticancer agents. They encompass proteases, ribosome inactivating proteins, defensins, hemolysins, lectins, laccases, ribonucleases, immunomodulatory proteins, and polysaccharopeptides. The target of the present review is to update the status of the various bioactivities of these fungal proteins and peptides and discuss their therapeutic potential. PMID:27338574

  8. LOUISIANA INVASIVE SPECIES PLAN

    EPA Science Inventory

    Identify the species, locations, and effects of invasive species within the state and the effects of these invasive species in Louisiana. Also identify how these species are spread, and the authorities that exist to manage and control them. With this information, create a m...

  9. Invasion of the Whiteflies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As invasive alien species spread, they often displace indigenous species, thus altering ecological communities and adversely affecting agricultural pest management, human health and well-being, and biodiversity. Despite the importance of invasive species, the processes enabling them to become estab...

  10. Non-invasive mechanical ventilation and epidural anesthesia for an emergency open cholecystectomy.

    PubMed

    Yurtlu, Bülent Serhan; Köksal, Bengü; Hancı, Volkan; Turan, Işıl Özkoçak

    2016-01-01

    Non-invasive ventilation is an accepted treatment modality in both acute exacerbations of respiratory diseases and chronic obstructive lung disease. It is commonly utilized in the intensive care units, or for postoperative respiratory support in post-anesthesia care units. This report describes intraoperative support in non-invasive ventilation to neuroaxial anesthesia for an emergency upper abdominal surgery. PMID:27591472

  11. Chemosensitization of fungal pathogens to antimicrobial agents using phenolic compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter describes the theory behind use of chemosensitization to control fungal pathogens. Oxidative stress response systems of fungal pathogens play important roles in protecting cells from reactive oxygen species (ROS) generated during host defense or environmental factors. Therefore, oxidati...

  12. MycoCosm, an Integrated Fungal Genomics Resource

    SciTech Connect

    Shabalov, Igor; Grigoriev, Igor

    2012-03-16

    MycoCosm is a web-based interactive fungal genomics resource, which was first released in March 2010, in response to an urgent call from the fungal community for integration of all fungal genomes and analytical tools in one place (Pan-fungal data resources meeting, Feb 21-22, 2010, Alexandria, VA). MycoCosm integrates genomics data and analysis tools to navigate through over 100 fungal genomes sequenced at JGI and elsewhere. This resource allows users to explore fungal genomes in the context of both genome-centric analysis and comparative genomics, and promotes user community participation in data submission, annotation and analysis. MycoCosm has over 4500 unique visitors/month or 35000+ visitors/year as well as hundreds of registered users contributing their data and expertise to this resource. Its scalable architecture allows significant expansion of the data expected from JGI Fungal Genomics Program, its users, and integration with external resources used by fungal community.

  13. Acute sacroiliitis.

    PubMed

    Slobodin, Gleb; Rimar, Doron; Boulman, Nina; Kaly, Lisa; Rozenbaum, Michael; Rosner, Itzhak; Odeh, Majed

    2016-04-01

    The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy. PMID:26847855

  14. Up-date on diagnostic strategies of invasive aspergillosis.

    PubMed

    Lackner, Michaela; Lass-Flörl, Cornelia

    2013-01-01

    Invasive fungal infections are a major cause of morbidity and mortality in immunosuppressed patients with fatality rates ranging from 30 % to 80 % in neutropenic patients. This results at least partly in difficulties obtaining a reliable and early diagnosis, followed by the fact that clinical symptoms are unspecific and of very limited use. Conventional methods may be difficult and are often delayed. Serological tests like the galactomannan enzyme immunoassay are presently most promising for diagnosing invasive aspergillosis, however, sensitivity and specificity vary within the studies. This review reflects the current situation of diagnosing invasive fungal infections with a special focus on how to best diagnose Aspergillus-related infections (e.g., culture, microscopy, imaging techniques, CT-guided biopsies). Promising molecular techniques under development will be discussed and their potential for routine diagnostic applications (e.g. lateral flow device, polymerase chain reaction [PCR]-based assays, rolling circle amplification [RCA], loop-mediated amplification [LAMP], nucleic acid sequence-based amplification [NASBA]). A summary is given on commercial assays (e.g., Platelia Aspergillus®, Fungitell®, in situ hybridization, immunohistochemisty) and their purposes as screening tools and/or diagnostic tools. This review gives a future outlook on how to best diagnose Aspergillus infections. PMID:23278540

  15. Neurons show the path: tip-to-nucleus communication in filamentous fungal development and pathogenesis.

    PubMed

    Etxebeste, Oier; Espeso, Eduardo A

    2016-09-01

    Multiple fungal species penetrate substrates and accomplish host invasion through the fast, permanent and unidirectional extension of filamentous cells known as hyphae. Polar growth of hyphae results, however, in a significant increase in the distance between the polarity site, which also receives the earliest information about ambient conditions, and nuclei, where adaptive responses are executed. Recent studies demonstrate that these long distances are overcome by signal transduction pathways which convey sensory information from the polarity site to nuclei, controlling development and pathogenesis. The present review compares the striking connections of the mechanisms for long-distance communication in hyphae with those from neurons, and discusses the importance of their study in order to understand invasion and dissemination processes of filamentous fungi, and design strategies for developmental control in the future. PMID:27587717

  16. Serum opsonin ficolin-A enhances host-fungal interactions and modulates cytokine expression from human monocyte-derived macrophages and neutrophils following Aspergillus fumigatus challenge.

    PubMed

    Bidula, Stefan; Sexton, Darren W; Schelenz, Silke

    2016-04-01

    Invasive aspergillosis is a devastating invasive fungal disease associated with a high mortality rate in the immunocompromised, such as leukaemia patients, transplant patients and those with HIV/AIDS. The rodent serum orthologue of human L-ficolin, ficolin-A, can bind to and opsonize Aspergillus fumigatus, the pathogen that causes invasive aspergillosis, and may participate in fungal defence. Using human monocyte-derived macrophages and neutrophils isolated from healthy donors, we investigated conidial association and fungal viability by flow cytometry and microscopy. Additionally, cytokine production was measured via cytometric bead arrays. Ficolin-A opsonization was observed to significantly enhance association of conidia, while also inhibiting hyphal growth and contributing to increased fungal killing following incubation with monocyte-derived macrophages and neutrophils. Additionally, ficolin-A opsonization was capable of manifesting a decrease in IL-8, IL-1β, IL-6, IL-10 and TNF-α production from MDM and IL-1β, IL-6 and TNF-α from neutrophils 24 h post-infection. In conclusion, rodent ficolin-A is functionally comparable to human L-ficolin and is capable of modulating the innate immune response to A. fumigatus, down-regulating cytokine production and could play an important role in airway immunity. PMID:26337048

  17. New advances in invasive aspergillosis immunobiology leading the way towards personalized therapeutic approaches.

    PubMed

    Obar, Joshua J; Hohl, Tobias M; Cramer, Robert A

    2016-08-01

    Invasive aspergillosis (IA) remains a devastating disease in immune compromised patients despite significant advances in our understanding of fungal virulence and host defense mechanisms. In this review, we summarize important research advances in the fight against IA with particular focus on early events in the interactions between Aspergillus fumigatus and the host that occur in the respiratory tract. Advances in understanding mechanisms of immune effector cell recruitment, antifungal effector mechanisms, and how the dynamic host-fungal interaction alters the local microenvironment to effect outcomes are highlighted. These advances illustrate exciting new therapeutic opportunities, but also emphasize the importance of understanding each unique fungus-host interaction for improving patient outcomes. PMID:27253487

  18. Exploiting fungal cell wall components in vaccines

    PubMed Central

    Levitz, Stuart M.; Huang, Haibin; Ostroff, Gary R.; Specht, Charles A.

    2014-01-01

    Innate recognition of fungi leads to strong adaptive immunity. Investigators are trying to exploit this observation in vaccine development by combining antigens with evolutionarily conserved fungal cell wall carbohydrates to induce protective responses. Best studied is β-1,3-glucan, a glycan that activates complement and is recognized by Dectin-1. Administration of antigens in association with β-1,3-glucan, either by direct conjugation or complexed in glucan particles, results in robust humoral and cellular immune responses. While the host has a host of mannose receptors, responses to fungal mannoproteins generally are amplified if cells are cooperatively stimulated with an additional danger signal such as a toll-like receptor agonist. Chitosan, a polycationic homopolymer of glucosamine manufactured by the deacetylation of chitin, is being studied as an adjuvant in DNA and protein-based vaccines. It appears particularly promising in mucosal vaccines. Finally, universal and organism-specific fungal vaccines have been formulated by conjugating fungal cell wall glycans to carrier proteins. A major challenge will be to advance these experimental findings so that at risk patients can be protected. PMID:25404118

  19. Fungal bioconversion of lignocellulosic residues; opportunities & perspectives.

    PubMed

    Dashtban, Mehdi; Schraft, Heidi; Qin, Wensheng

    2009-01-01

    The development of alternative energy technology is critically important because of the rising prices of crude oil, security issues regarding the oil supply, and environmental issues such as global warming and air pollution. Bioconversion of biomass has significant advantages over other alternative energy strategies because biomass is the most abundant and also the most renewable biomaterial on our planet. Bioconversion of lignocellulosic residues is initiated primarily by microorganisms such as fungi and bacteria which are capable of degrading lignocellulolytic materials. Fungi such as Trichoderma reesei and Aspergillus niger produce large amounts of extracellular cellulolytic enzymes, whereas bacterial and a few anaerobic fungal strains mostly produce cellulolytic enzymes in a complex called cellulosome, which is associated with the cell wall. In filamentous fungi, cellulolytic enzymes including endoglucanases, cellobiohydrolases (exoglucanases) and beta-glucosidases work efficiently on cellulolytic residues in a synergistic manner. In addition to cellulolytic/hemicellulolytic activities, higher fungi such as basidiomycetes (e.g. Phanerochaete chrysosporium) have unique oxidative systems which together with ligninolytic enzymes are responsible for lignocellulose degradation. This review gives an overview of different fungal lignocellulolytic enzymatic systems including extracellular and cellulosome-associated in aerobic and anaerobic fungi, respectively. In addition, oxidative lignocellulose-degradation mechanisms of higher fungi are discussed. Moreover, this paper reviews the current status of the technology for bioconversion of biomass by fungi, with focus on mutagenesis, co-culturing and heterologous gene expression attempts to improve fungal lignocellulolytic activities to create robust fungal strains. PMID:19774110

  20. 50-plus years of fungal viruses

    SciTech Connect

    Ghabrial, Said A.; Castón, José R.; Nibert, Max L.; Suzuki, Nobuhiro

    2015-05-15

    Mycoviruses are widespread in all major taxa of fungi. They are transmitted intracellularly during cell division, sporogenesis, and/or cell-to-cell fusion (hyphal anastomosis), and thus their life cycles generally lack an extracellular phase. Their natural host ranges are limited to individuals within the same or closely related vegetative compatibility groups, although recent advances have established expanded experimental host ranges for some mycoviruses. Most known mycoviruses have dsRNA genomes packaged in isometric particles, but an increasing number of positive- or negative-strand ssRNA and ssDNA viruses have been isolated and characterized. Although many mycoviruses do not have marked effects on their hosts, those that reduce the virulence of their phytopathogenic fungal hosts are of considerable interest for development of novel biocontrol strategies. Mycoviruses that infect endophytic fungi and those that encode killer toxins are also of special interest. Structural analyses of mycoviruses have promoted better understanding of virus assembly, function, and evolution. - Highlights: • Historical perspective of fungal virus research. • Description, classification and diversity of fungal virus families. • Structural features of fungal virus particles. • Hypovirulence and exploitation of mycoviruses in biological control of plant pathogenic fungi.