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Invasive fungal infections

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https://www.readbyqxmd.com/read/29330691/bis-guanylhydrazones-as-efficient-anti-candida-compounds-through-dna-interaction
#1
Jelena Lazić, Vladimir Ajdačić, Sandra Vojnovic, Mario Zlatović, Marina Pekmezovic, Selene Mogavero, Igor Opsenica, Jasmina Nikodinovic-Runic
Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone- and guanidine-containing molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C...
January 12, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29327534/gastric-angioinvasive-mucormycosis-in-immunocompetent-adult-a-rare-occurrence
#2
Mukesh Nasa, Zubin Sharma, Lipika Lipi, Randhir Sud
Mucormycosis is a rare, opportunistic fungal infection that occurs almost exclusively in immunocompromised hosts such as patients with diabetes mellitus, leukemia, lymphoma, renal disease, septicemia, burns, malnutrition, and following long-term treatment with steroids and antibiotics. Based on the clinical presentation and involvement, mucormycosis is classified as six major forms, namely, rhinocerebral, pulmonary, cutaneous, gastrointestinal (GI), disseminated and miscellaneous, with rhinocerebral and pulmonary being the common forms...
December 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29325818/simultaneous-determination-of-voriconazole-posaconazole-itraconazole-and-hydroxy-itraconazole-in-human-plasma-using-lcms-ms
#3
Nicole Jenkins, Marion Black, Hans G Schneider
INTRODUCTION: Invasive fungal infections are an increasing cause of mortality and morbidity in high risk patient populations such as those on immunosuppressive therapy. Triazole antifungals are recommended for the prevention and treatment of such infections. The aim of this study was to develop and validate a simple, sensitive and robust LCMS/MS method for the simultaneous analysis in human plasma of three frequently used antifungal drugs: voriconazole, posaconazole, and itraconazole...
January 8, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29323188/a-tet-off-gene-expression-system-for-validation-of-antifungal-drug-targets-in-a-murine-invasive-pulmonary-aspergillosis-model
#4
Yutian Peng, Hua Zhang, Min Xu, Man-Wah Tan
Aspergillus fumigatus is one of the major causes of invasive pulmonary aspergillosis in immunocompromised patients. Novel antifungal therapy is in urgent need due to emerging resistance and adverse toxicity of current antifungal drugs. Gene products that are essential for Aspergillus viability during infection are attractive drug targets. To characterize these genes in vivo we developed a Tet-Off gene expression system in A. fumigatus, whereby the administration of doxycycline resulted in down regulation of the gene whose expression is under the control of the Tet-Off promoter...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315506/optimization-of-voriconazole-therapy-for-the-treatment-of-invasive-fungal-infections-in-adults
#5
Naveen Mangal, Issam Hamadeh, Meghan J Arwood, Larisa H Cavallari, Tanay S Samant, Kenneth P Klinker, Jurgen Bulitta, Stephan Schmidt
Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using drug monitoring approach, which relies on attainment of steady state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses which can maximize the net benefit (probability of efficacy - probability of adverse events) and ensure therapeutic concentrations, early on during treatment...
January 9, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29315021/the-global-regulatory-protein-vela-is-required-for-symbiosis-between-the-endophytic-fungus-epichlo%C3%A3-festucae-and-lolium-perenne
#6
Mostafa Rahnama, Richard Johnson, Christine Rosalie Voisey, Wayne R Simpson, Damien J Fleetwood
Epichloë species fungi form bioprotective endophytic symbioses with many cool-season grasses, including agriculturally important forage grasses. Despite its importance, relatively little is known about the molecular details of the interaction and the regulatory genes involved. One of the key global regulators in fungal secondary metabolism and development is the VelA protein. In this study, velA was functionally characterised in vitro and in fungal interaction with its host perennial ryegrass. The velA gene is required for E...
January 9, 2018: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29313961/impaired-phagocytosis-directs-human-monocyte-activation-in-response-to-fungal-derived-%C3%AE-glucan-particles
#7
Giorgio Camilli, Elif Eren, David L Williams, Vishukumar Aimanianda, Etienne Meunier, Jessica Quintin
Recognition of the fungal cell wall carbohydrate β-glucan by the host receptor Dectin-1 elicits broad immunomodulatory responses, such as phagocytosis and activation of oxidative burst. These responses are essential for engulfing and killing fungal pathogens. Phagocytic monocytes are key mediators of these early host inflammatory responses to infection. Remarkably, whether phagocytosis of fungal β-glucan leads to an inflammatory response in human monocytes remains to be established. Here, we show that phagocytosis of heat-killed Candida albicans is essential to trigger inflammation and cytokine release...
January 5, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29311082/deletion-of-ada2-increases-antifungal-drug-susceptibility-and-virulence-in-candida-glabrata
#8
Shang-Jie Yu, Ya-Lin Chang, Ying-Lien Chen
Candida glabrata, the second most frequent cause of candidiasis after Candida albicans, is an emerging human fungal pathogen that is intrinsically drug tolerant. Currently, studies of C. glabrata genes involved in drug tolerance are limited. Ada2, a component serving as a transcription adaptor of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, is required for antifungal drug tolerance and virulence in C. albicans However, its roles in C. glabrata remain elusive. In this study, we found that ada2 mutants demonstrated severe growth defects at 40°C but only mild defects at 37°C or 25°C...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29311065/in-vitro-and-in-vivo-evaluation-of-the-antifungal-activity-of-apx001a-apx001-against-candida-auris
#9
Christopher L Hager, Emily L Larkin, Lisa Long, Fatima Z Abidi, Karen J Shaw, Mahmoud A Ghannoum
Candida auris is an emerging multidrug-resistant yeast that has been responsible for invasive infections associated with high morbidity and mortality. C. auris strains often demonstrate high fluconazole and amphotericin B minimum inhibitory concentration values, and some strains are resistant to all 3 major antifungal classes. Here we evaluated the susceptibility of 16 C. auris clinical strains, isolated from a wide geographical area, to 10 antifungal agents including APX001A, a novel agent that inhibits the fungal protein Gwt1 (GPI-anchored wall transfer protein 1)...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29310378/isolated-cerebral-aspergillosis-in-an-immunocompetent-woman-on-treatment-for-bacterial-infected-necrotizing-pancreatitis-a-case-report
#10
Shaoyang Zhang, Qinghui Fu, Qi Chen, Ting-Bo Liang
RATIONALE: Cerebral aspergillosis (CA) is a rare manifestation of invasive aspergillosis. It usually affects seriously immunocompromised hosts. Pancreatic bacterial or/and fungal infection is common in patients with severe acute pancreatitis. PATIENT CONCERNS: We report the first case of an immunocompetent woman with infected necrotizing pancreatitis due to multidrug resistant Acinetobacter baumannii who, in the course of treatment, developed isolated CA. DIAGNOSES: Magnetic resonance imaging, rather than computed tomography, revealed latent homolateral sinus disease-the possible source of the Aspergillus infection...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29306852/trichosporon-asahii-septic-thrombophlebitis-following-lower-extremity-amputation-in-an-immunocompetent-host
#11
Pradeep Kumar Mada, Folusakin Ayoade, Ailing Li, John Todd
A 59-year-old man with a history of peripheral vascular disease status post femoral popliteal bypass presented with critical limb ischaemia of the left leg. An arterial Doppler ultrasound showed an occluded graft requiring an above knee amputation. Five days after surgery, the patient developed fever, leucocytosis, significant stump swelling and pain, and serosanguinous discharge from his wound. Wound swab cultures from the stump grew Trichosporon asahii A venous Doppler ultrasound revealed extensive thrombosis of the left lower extremity...
January 6, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29304213/echinocandin-prophylaxis-in-patients-undergoing-haematopoietic-cell-transplantation-and-other-treatments-for-haematological-malignancies
#12
David J Epstein, Susan K Seo, Janice M Brown, Genovefa A Papanicolaou
Antifungal prophylaxis is the standard of care for patients undergoing intensive chemotherapy for haematological malignancy or haematopoietic cell transplantation (HCT). Prophylaxis with azoles reduces invasive fungal infections and may reduce mortality. However, breakthrough infections still occur, and the use of azoles is sometimes complicated by pharmacokinetic variability, drug interactions, adverse events and other issues. Echinocandins are highly active against Candida species, including some organisms resistant to azoles, and have some clinical activity against Aspergillus species as well...
January 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29304212/use-of-echinocandin-prophylaxis-in-solid-organ-transplantation
#13
Maddalena Giannella, Shahid Husain, Faouzi Saliba, Pierluigi Viale
Invasive fungal infections (IFIs) are a major threat to patients undergoing solid organ transplantation (SOT). Owing to improvements in surgical techniques, immunosuppression therapy and antifungal prophylaxis, the incidence of IFIs has been decreasing in recent years. However, IFI-associated morbidity and mortality remain significant. Invasive candidiasis (IC) and aspergillosis (IA) are the main IFIs after SOT. Risk factors for IC and IA continue to evolve, and thus strategies for their prevention should be constantly updated and targeted to both individual patient risk factors and local epidemiology...
January 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29295913/o-mannosylation-of-proteins-enables-histoplasma-yeast-survival-at-mammalian-body-temperatures
#14
Andrew L Garfoot, Kristie D Goughenour, Marcel Wüthrich, Murugesan V S Rajaram, Larry S Schlesinger, Bruce S Klein, Chad A Rappleye
The ability to grow at mammalian body temperatures is critical for pathogen infection of humans. For the thermally dimorphic fungal pathogen Histoplasma capsulatum, elevated temperature is required for differentiation of mycelia or conidia into yeast cells, a step critical for invasion and replication within phagocytic immune cells. Posttranslational glycosylation of extracellular proteins characterizes factors produced by the pathogenic yeast cells but not those of avirulent mycelia, correlating glycosylation with infection...
January 2, 2018: MBio
https://www.readbyqxmd.com/read/29290576/leukotriene-b4-mediated-neutrophil-recruitment-causes-pulmonary-capillaritis-during-lethal-fungal-sepsis
#15
Esther K S Lee, Mark R Gillrie, Lu Li, Jason W Arnason, Jung Hwan Kim, Liane Babes, Yuefei Lou, Amir Sanati-Nezhad, Stephen K Kyei, Margaret M Kelly, Christopher H Mody, May Ho, Bryan G Yipp
Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C. albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C. albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival...
December 28, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29286213/risk-factors-for-invasive-fungal-infection-among-thai-oncologic-patients-with-febrile-neutropenia-and-cutaneous-presentation-a-5-year-retrospective-study-in-southern-thailand
#16
Kumpol Aiempanakit, Surarit Naorungroj, Kanokphorn Chiratikarnwong, Sauvarat Auepemkiate, Benjawan Apinantriyo
Background: Febrile neutropenia (FNP) is a condition defined by fever and neutropenia. There are current only limited data on related cutaneous manifestations. This study aimed to assess cutaneous lesions and their etiologies in a Thai group of FNP patients. Methods: A retrospective analysis was conducted on 43 non-transplant febrile neutropenic patients with concurrent cutaneous lesions, as determined by dermatopathologic studies at Songklanagarind Hospital in Thailand over a five-year period. Results: The mean age was 39 years (SD: 18...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29281997/meta-analysis-of-the-safety-of-voriconazole-in-definitive-empirical-and-prophylactic-therapies-for-invasive-fungal-infections
#17
Yuanming Xing, Lu Chen, Yan Feng, Yan Zhou, Yajing Zhai, Jun Lu
BACKGROUND: Voriconazole has been used in the treatment and prophylaxis of invasive fungal infections (IFIs) while its wide use was limited by some frequent adverse events, especially neurotoxicity, hepatotoxicity and even renal disruption. The aim of this study was to comprehensively compare voriconazole-induced toxicity, including tolerability, neurotoxicity, visual toxicity, hepatotoxicity and nephrotoxicity with the composite of other antifungals commonly used in clinic. METHODS: Bibliography databases were searched to select randomized controlled trials providing information about the incidence of toxicity referred above...
December 28, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29281994/successful-treatment-of-cerebral-aspergillosis-case-report-of-a-patient-with-t-cell-large-granular-lymphocytic-leukemia-t-lgl
#18
Amin T Turki, Jassin Rashidi-Alavijeh, Jan Dürig, Guido Gerken, Peter-Michael Rath, Oliver Witzke
BACKGROUND: Invasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients...
December 28, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29274212/drug-susceptibility-of-fungi-isolated-from-icu-patients
#19
Barbara D Modrzewska, Anna J Kurnatowska,, Katarzyna Khalid
Candida species can be a reason of infections associated with high morbidity and mortality. The risk of invasive candidosis for patients admitted to intensive care units (ICUs) is increased due to immunosuppressive states, prolonged length of stay, broad-spectrum antibiotics and Candida colonization. The aim of the study was to determine selected properties of fungi isolated from patients treated in the ICUs of hospitals in Lodz. The materials were collected from the oral cavity, the tracheostomy or endotracheal tube and urine from 16 children and 35 adult...
2017: Annals of Parasitology
https://www.readbyqxmd.com/read/29251580/successful-treatment-of-lung-aspergillus-terreus-infection-after-a-second-hematopoietic-stem-cell-transplant-in-a-patient-with-myelodysplastic-syndrome
#20
Yu Zhang, Junfa Chen, Lili Qian, Xuejing Yang, Jianping Shen
A 24-year-old man was diagnosed with myelodysplastic syndrome and received a haploidentical hematopoietic stem cell transplant. The patient experienced graft failure posttransplant. Analysis of specific antibodies revealed that the patient had strongly positive donor-specific antibodies; therefore, we changed the donor to the patient's mother and added a single unit of cord blood to perform the second transplant. Corresponding treatments targeting donor-specific antibodies were administered to reverse the graft rejection and to reduce the antibody load...
December 18, 2017: Experimental and Clinical Transplantation
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