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Invasive aspergillosis

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https://www.readbyqxmd.com/read/28928005/sensitive-and-selective-quantification-of-total-and-free-itraconazole-and-hydroxyitraconazole-in-human-plasma-using-ultra-performance-liquid-chromatography-coupled-to-tandem-mass-spectrometry
#1
Yosuke Suzuki, Ryota Tanaka, Nobuhiro Oyama, Ko Nonoshita, Kazuhiko Hashinaga, Kenji Umeki, Yuhki Sato, Kazufumi Hiramatsu, Jun-Ichi Kadota, Hiroki Itoh
OBJECTIVES: Protein-free (unbound) drug concentrations have been reported to be better biomarker of pharmacodynamics compared with total drug concentrations. In this study, we developed and validated an assay for the quantification of total and free itraconazole and hydroxyitraconazole, a main metabolite with antifungal activity, in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). DESIGN & METHODS: Plasma sample was ultra-filtrated for the measurement of free itraconazole and hydroxyitraconazole concentrations...
September 16, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28927200/epidemiology-of-invasive-fungal-disease-in-children
#2
Zoi Dorothea Pana, Emmanuel Roilides, Adilia Warris, Andreas H Groll, Theoklis Zaoutis
Considerable progress has been made in the prevention, diagnosis, and management of pediatric patients with invasive fungal disease (IFD). The reported decreasing trend in the incidence of invasive candidiasis (IC) over the past 15 years in both neonates and children has been encouraging. Nevertheless, due to the growing number of immunocompromised children at risk for IFD, this disease continues to be associated with significant morbidity and death and with increased financial burden to the health care system...
September 1, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28924369/il-12-influence-mtor-to-modulate-cd8-t-cells-differentiation-through-t-bet-and-eomesodermin-in-response-to-invasive-pulmonary-aspergillosis
#3
Hao Wang, Jingdong Li, Qiyang Han, Fei Yang, Yu Xiao, Meng Xiao, Yingchun Xu, Longxiang Su, Na Cui, Dawei Liu
Objective: To investigate whether mTOR signaling pathway regulate the proliferation and differentiation of CD8(+) T cells by transcription factors T-bet and Eomes, and explore the role of IL-12 in this biological procedure. Methods: Aspergillus fumigatus spore suspension nasal inhalation was used to establish the invasive pulmonary aspergillosis (IPA) mouse model. After inoculation, rapamycin (2mg/kg) each day or IL-12 (5ug/kg) every other day was given for 7 days. The blood samples were obtained before the mice sacrificed and lung specimens were taken...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28923872/exposure-response-relationships-for-isavuconazole-in-patients-with-invasive-aspergillosis-and-other-filamentous-fungi
#4
Amit V Desai, Laura L Kovanda, William W Hope, David Andes, Johan W Mouton, Donna L Kowalski, Robert W Townsend, Salim Mujais, Peter L Bonate
Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and other filamentous fungi from the SECURE trial. Two hundred and thirty one patients who received the clinical dosing regimen and had exposure parameters were included in this analysis...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28922489/clinical-evaluation-of-the-newly-formatted-lateral-flow-device-for-invasive-pulmonary-aspergillosis
#5
Martin Hoenigl, Susanne Eigl, Sven Heldt, Wiebke Duettmann, Christopher Thornton, Juergen Prattes
The study evaluated the newly formatted Aspergillus-specific lateral-flow-device (LFD), and compared its performance to the original prototype "old" LFD test using BALF samples from 28 patients (14 patients with probable/proven invasive pulmonary aspergillosis [IPA] and 14 patients with no evidence for IPA). A total of 10/14 (71%) of BALF samples from patients with probable/proven IPA resulted positive with the new LFD, including 8/9 with true-positive and 2/5 with false-negative results with the old LFD. All 14 samples from patients without IPA resulted negative with the new LFD; specificity of the new LFD was significantly improved compared to the old LFD...
September 18, 2017: Mycoses
https://www.readbyqxmd.com/read/28919635/aspergillus-fumigatus-morphology-and-dynamic-host-interactions
#6
REVIEW
Frank L van de Veerdonk, Mark S Gresnigt, Luigina Romani, Mihai G Netea, Jean-Paul Latgé
Aspergillus fumigatus is an environmental filamentous fungus that can cause life-threatening disease in immunocompromised individuals. The interactions between A. fumigatus and the host environment are dynamic and complex. The host immune system needs to recognize the distinct morphological forms of A. fumigatus to control fungal growth and prevent tissue invasion, whereas the fungus requires nutrients and needs to adapt to the hostile environment by escaping immune recognition and counteracting host responses...
September 18, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28912884/towards-translational-immunopet-mr-imaging-of-invasive-pulmonary-aspergillosis-the-humanised-monoclonal-antibody-jf5-detects-aspergillus-lung-infections-in-vivo
#7
Genna Davies, Anna-Maria Rolle, Andreas Maurer, Philipp R Spycher, Claudia Schillinger, Djamschid Solouk-Saran, Mike Hasenberg, Juliane Weski, Jesper Fonslet, Adrien Dubois, Frederic Boschetti, Franck Denat, Matthias Gunzer, Martin Eichner, Lauren S Ryder, Mikael Jensen, Roger Schibli, Bernd J Pichler, Stefan Wiehr, Christopher R Thornton
Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [(64)Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus...
2017: Theranostics
https://www.readbyqxmd.com/read/28911046/animal-models-for-studying-triazole-resistance-in-aspergillus-fumigatus
#8
Russell E Lewis, Paul E Verweij
Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28911045/azole-resistant-aspergillosis-epidemiology-molecular-mechanisms-and-treatment
#9
Anuradha Chowdhary, Cheshta Sharma, Jacques F Meis
Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Triazoles are the mainstay of therapy against Aspergillus infections for treatment and prophylaxis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28905439/testing-the-performance-of-a-prototype-lateral-flow-device-using-bronchoalveolar-lavage-fluid-for-the-diagnosis-of-invasive-pulmonary-aspergillosis-in-high-risk-patients
#10
Caroline G Castillo, Carol A Kauffman, Jingyi Zhai, Hui Jiang, Stephanie M Agozino, Marisa H Miceli
The diagnosis of invasive pulmonary aspergillosis (IPA) increasingly relies on non-culture-based biomarkers in bronchoalveolar lavage (BAL) fluid. The Aspergillus lateral flow device (LFD) is a rapid immunoassay that uses a novel Aspergillus monoclonal antibody to gain specificity. The objective of the study is to compare specificity and sensitivity of the prototype LFD and the galactomannan (GM) enzyme immunoassay in BAL fluid in high-risk patients. A total of 114 BAL samples from 106 patients at high risk for IPA were studied: 8 patients had proven/probable IPA, 16 had possible IPA and 82 did not have IPA...
September 14, 2017: Mycoses
https://www.readbyqxmd.com/read/28903985/molecular-tools-for-the-detection-and-deduction-of-azole-antifungal-drug-resistance-phenotypes-in-aspergillus-species
#11
REVIEW
Anna Dudakova, Birgit Spiess, Marut Tangwattanachuleeporn, Christoph Sasse, Dieter Buchheidt, Michael Weig, Uwe Groß, Oliver Bader
The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients...
October 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28893772/triazole-resistance-is-still-not-emerging-in-a-fumigatus-isolates-causing-invasive-aspergillosis-in-brazilian-patients
#12
Clara E Negri, Sarah S Gonçalves, Ana Cristina P Sousa, Maria Daniela Bergamasco, Marinês D V Martino, Flavio Queiroz-Telles, Valerio Rodrigues Aquino, Paulo de Tarso O Castro, Ferry Hagen, Jacques F Meis, Arnaldo L Colombo
Aspergillus fumigatus azole resistance has globally emerged as a health problem. We evaluated the in vitro antifungal susceptibility of 221 clinical A. fumigatus isolates according to CLSI. Sixty-one isolates exhibiting MIC at the epidemiological cut-off value (ECV) for itraconazole or above ECV for any triazole were checked for CYP51A mutations. No mutations were documented, even for four isolates (1.8%) with high voriconazole MICs, indicating that triazoles may be safely used to treat aspergillosis in Brazil...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28892890/virulence-factors-detection-in-aspergillus-isolates-from-clinical-and-environmental-samples
#13
Raksha, Gurjeet Singh, A D Urhekar
INTRODUCTION: Pathogenesis of aspergillosis is dependent on various factors of the host (immune status) and virulence factors of the pathogen which could play a significant role in the pathogenesis of invasive aspergillosis. AIM: To study the virulence factors of Aspergillus species isolated from patient samples and environmental samples. MATERIALS AND METHODS: This prospective and experimental study was carried out at Department of Microbiology, MGM Medical College and Hospital, Mumbai, Maharashtra, India, from July 2014 to June 2015...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28887465/host-immune-status-specific-production-of-gliotoxin-and-bis-methyl-gliotoxin-during-invasive-aspergillosis-in-mice
#14
Janyce A Sugui, Stacey R Rose, Glenn Nardone, Muthulekha Swamydas, Chyi-Chia R Lee, Kyung J Kwon-Chung, Michail S Lionakis
Delayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth and may prove diagnostically useful. Because IA pathophysiology and GT's role in virulence vary depending on the underlying host immune status, we hypothesized that GT and bmGT production in vivo may differ in three mouse models of IA that mimic human disease. We defined temporal kinetics of GT and bmGT in serum, bronchoalveolar lavage fluid (BALF) and lungs of A...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883073/sterilizing-immunity-in-the-lung-relies-on-targeting-fungal-apoptosis-like-programmed-cell-death
#15
Neta Shlezinger, Henriette Irmer, Sourabh Dhingra, Sarah R Beattie, Robert A Cramer, Gerhard H Braus, Amir Sharon, Tobias M Hohl
Humans inhale mold conidia daily and typically experience lifelong asymptomatic clearance. Conidial germination into tissue-invasive hyphae can occur in individuals with defects in myeloid function, although the mechanism of myeloid cell-mediated immune surveillance remains unclear. By monitoring fungal physiology in vivo, we demonstrate that lung neutrophils trigger programmed cell death with apoptosis-like features in Aspergillus fumigatus conidia, the most prevalent human mold pathogen. An antiapoptotic protein, AfBIR1, opposes this process by inhibiting fungal caspase activation and DNA fragmentation in the murine lung...
September 8, 2017: Science
https://www.readbyqxmd.com/read/28882011/comments-on-practice-guidelines-for-the-diagnosis-and-management-of-aspergillosis-made-by-the-idsa-in-2016
#16
REVIEW
E Alarcón-Manoja, C Cardozo-Espinola, P Puerta-Alcalde, C García-Vidal
We sought to review the most important updates in the treatment of aspergillosis after the publication of the clinical practice guidelines for the diagnosis and management of invasive aspergillosis (IA) by the Infectious Diseases Society of America. Our aim is to discuss some of the key aspects concerning the following topics: early initiation of antifungal therapy, antifungal agent of choice, follow-up of patients with IA, and breakthrough aspergillosis.
September 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28882009/update-on-the-diagnosis-of-invasive-fungal-infection
#17
REVIEW
E Ibáñez-Martínez, A Ruiz-Gaitán, J Pemán-García
The number of patients at risk of suffering invasive fungal infection (IFI) is increasing. Because of its high mortality, new rapid and accurate diagnostic tools are needed. Last advances in invasive candidiasis diagnosis comprise Peptide Nucleic Acid Fluorescent In-Situ Hybridization (PNA-FISH), direct MALDI-TOF or multiplex acid nucleic testing. While all of them rely in positive blood cultures, T2Candida uses PCR coupled with T2Magnetic resonance detection directly in whole blood, allowing detection of 1-3 UFC/mL of Candida in about four hours...
September 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28878289/persistence-within-dendritic-cells-marks-an-antifungal-evasion-and-dissemination-strategy-of-aspergillus-terreus
#18
Shih-Hung Hsieh, Oliver Kurzai, Matthias Brock
Aspergillus terreus is an airborne human fungal pathogen causing life-threatening invasive aspergillosis in immunocompromised patients. In contrast to Aspergillus fumigatus, A. terreus infections are associated with high dissemination rates and poor response to antifungal treatment. Here, we compared the interaction of conidia from both fungal species with MUTZ-3-derived dendritic cells (DCs). After phagocytosis, A. fumigatus conidia rapidly escaped from DCs, whereas A. terreus conidia remained persisting with long-term survival...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877383/levels-of-interleukin-il-6-and-il-8-are-elevated-in-serum-and-bronchoalveolar-lavage-fluid-of-haematological-patients-with-invasive-pulmonary-aspergillosis
#19
Sven Heldt, Susanne Eigl, Juergen Prattes, Holger Flick, Jasmin Rabensteiner, Florian Prüller, Tobias Niedrist, Peter Neumeister, Albert Wölfler, Heimo Strohmaier, Robert Krause, Martin Hoenigl
Aspergillus spp. have been shown to induce T-helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case-control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014-2017) adult cases with underlying haematological malignancies and suspected pulmonary infection...
September 6, 2017: Mycoses
https://www.readbyqxmd.com/read/28865757/a-cell-impedance-based-real-time-in-vitro-assay-to-assess-the-toxicity-of-amphotericin-b-formulations
#20
Jean Menotti, Alexandre Alanio, Aude Sturny-Leclère, Sandrine Vitry, Félix Sauvage, Gillian Barratt, Stéphane Bretagne
Aerosolized liposomal amphotericin B (L-AmB) has been investigated as prophylaxis against invasive aspergillosis. However, the clinical results are controversial and some trials suggest that toxicity could be a limitation for wider use. Our aim was to assess the dynamics of cell toxicity induced in a human alveolar epithelial cell line (A549) after exposure to L-AmB (50 to 400μg/ml) or amphotericin B deoxycholate (D-AmB; 50 to 200μg/ml) by monitoring real-time A549 cell viability using an impedance-based technology...
September 1, 2017: Toxicology and Applied Pharmacology
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