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https://www.readbyqxmd.com/read/28340159/detection-of-polish-clinical-aspergillus-fumigatus-isolates-resistant-to-triazoles
#1
Urszula Nawrot, Ewelina Kurzyk, Maiken Cavling Arendrup, Martyna Mroczynska, Katarzyna Wlodarczyk, Beata Sulik-Tyszka, Marta Wróblewska, Marek Ussowicz, Przemyslaw Zdziarski, Kinga Niewinska, Anna Brillowska-Dabrowska
We studied the presence of triazole resistance of 121 Aspergillus fumigatus clinical isolates collected in two Polish cities, Warsaw and Wrocław, to determine if resistance is emerging in our country. We identified five itraconazole resistant isolates (4.13%) carrying the TR34/L98H alteration in Cyp51A gene, four of which were cross-resistant to posaconazole and one to voriconazole. One isolate was intermediate susceptible to itraconazole and harbored no Cyp51A alterations. The study confirms the presence of azole resistant A...
March 4, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28333310/dihydroorotate-dehydrogenase-inhibitor-f901318-has-potent-in-vitro-activity-against-scedosporium-species-and-lomentospora-prolificans
#2
Nathan P Wiederhold, Derek Law, Michael Birch
Background: Scedosporium species and Lomentospora prolificans are increasing causes of invasive infections in immunocompromised hosts and many isolates are resistant to available antifungals. Our objective was to assess the in vitro potency of F901318, a member of the orotomide class of antifungals, against Scedosporium species and L. prolificans . Methods: The in vitro potency of F901318 was evaluated against 66 Scedosporium and 7 L. prolificans clinical isolates using the CLSI M38-A2 reference standard...
March 15, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28331021/aspergillus-niger-infection-in-an-immunosuppressed-patient-confined-solely-to-the-brain
#3
Lucy Simmonds, Sian Mitchell, Barrie White, Shanika A Crusz, David Denning
A 68-year-old woman with a background of hypertension, stroke and rheumatoid arthritis presented to her local hospital after a 4-week history of gradual deterioration and increasing confusion with new onset right-sided weakness. Her initial CT scan revealed a rim enhancing mass lesion with surrounding oedema in the left parietal lobe for which she underwent CT stealth-guided biopsy. Microbiology culture of the 2 biopsy samples yielded Aspergillus niger and she was started on the antifungal agent voriconazole...
March 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#4
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28303848/triazole-resistance-in-aspergillus-fumigatus-clinical-isolates-obtained-in-nanjing-china
#5
Ming Zhang, Chun-Lai Feng, Fei Chen, Qian He, Xin Su, Yi Shi
BACKGROUND: During the past decades, the incidence of invasive aspergillosis (IA) caused by Aspergillus fumigatus has increased dramatically. The aims of this study were to investigate the susceptibility of clinical isolates of A. fumigatus to triazole and the underlying cyp51A mutations in triazole-resistant A. fumigatus. METHODS: A total of 126 A. fumigatus clinical isolates from 126 patients with proven or probable IA were obtained from four large tertiary hospitals in Nanjing, China, between August 2012 and July 2015...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28299646/hyperlipidemia-alters-the-pharmacokinetics-of-posaconazole-and-vincristine-upon-co-administration-in-rats
#6
Hadeel A Khalil, Mohammed A W ElKhatib, Tarek S Belal, Ahmed F El-Yazbi, Dalia A Hamdy
OBJECTIVES: Co-administration of posaconazole (PSZ) and vincristine (VCR) in the treatment of patients with acute lymphoblastic leukemia increases the neurotoxicity of VCR. Our aim is to study the effect of increased lipoprotein levels on the pharmacokinetics of PSZ and VCR upon co-administration in rats. METHODS: Rats were assigned to three groups, normolipidemic (NL), intermediate hyperlipidemic (IHL), and extreme hyperlipidemic (HL) groups. All rats were administered PSZ orally followed by VCR intravenously 4 h later...
March 15, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28295973/cutaneous-phaeohyphomycosis-in-a-hematopoietic-stem-cell-transplant-patient-caused-by-alternaria-rosae-first-case-report
#7
Amy W Liu, Allen C Bateman, Adam Greenbaum, Kanishka Garvin, Jill Clarridge, Jonathan Grim
Alternaria species have been reported as a rare cause of fungal infection in organ and stem cell transplant recipients, but to date no reports have been published of infection in humans caused by Alternaria rosae. Here, we report cutaneous A. rosae infection in a 66-year-old farmer with a history of primary myelofibrosis who had undergone allogeneic unrelated donor hematopoietic stem cell transplantation. Forty-nine days post transplant, he presented with a nodule on the thumb with no findings suggestive of disseminated infection...
March 13, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28282366/comparing-azole-plasma-trough-levels-in-lung-transplant-recipients-percentage-of-therapeutic-levels-and-intrapatient-variability
#8
Daniela Stelzer, Alexandra Weber, Franziska Ihle, Sandhya Matthes, Felix Ceelen, Gregor Zimmermann, Nikolaus Kneidinger, Rene Schramm, Hauke Winter, Michael Zoller, Michael Vogeser, Juergen Behr, Claus Neurohr
BACKGROUND: This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intrapatient variability for each azole was determined. METHODS: From July 2012 to July 2015, 806 APL of ITR, VOR, posaconazole liquid (POS-Liq), and posaconazole tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation Program...
April 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28273390/purpureocillium-lilacinum-tattoo-related-skin-infection-in-a-kidney-transplant-recipient
#9
Sonya A Trinh, Michael P Angarone
Purpureocillium lilacinum is an emerging pathogenic mold among immunocompromised hosts that causes cutaneous infections related to skin breakdown. We present the first reported case of P. lilacinum tattoo-related skin infection, to our knowledge. A kidney transplant recipient recently treated for acute cellular rejection presented with skin papules overlying a tattoo. Diagnosis was confirmed on culture, histology, and 18s ribosomal RNA polymerase chain reaction. The morphological features on culture characteristic of P...
March 8, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28264849/genetic-diversity-and-in-vitro-antifungal-susceptibility-of-200-clinical-and-environmental-aspergillus-flavus-isolates
#10
Mojtaba Taghizadeh-Armaki, Mohammad Taghi Hedayati, Saham Ansari, Saeed Mahdavi Omran, Sasan Saber, Haleh Rafati, Jan Zoll, Henrich A van der Lee, Willem J G Melchers, Paul E Verweij, Seyedmojtaba Seyedmousavi
Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and sub-tropical countries.Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial β-tubulin and calmodulin genes. In vitro antifungal susceptibility testing was performed against antifungals using the EUCAST (European Committee on Antimicrobial Susceptibility Testing) broth microdilution method...
March 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28264840/prophylaxis-with-isavuconazole-or-posaconazole-protect-immunosuppressed-mice-from-pulmonary-mucormycosis
#11
Teclegiorgis Gebremariam, Sondus Alkhazraji, Clara Baldin, Laura Kovanda, Nathan P Wiederhold, Ashraf S Ibrahim
We assessed prophylactic or continuous therapy of isavuconazole, posaconazole or voriconazole in treating pulmonary murine mucormycosis. In the prophylaxis studies, only isavuconazole treatment resulted in significantly improved survival and lowered tissue fungal burden of immunosuppressed mice infected with Rhizopus delemar. In the continuous treatment studies, isavuconazole and posaconazole, but not voriconazole, equally prolonged survival time and lowered tissue fungal burden versus placebo-treated mice...
March 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28258343/efficacy-safety-and-feasibility-of-antifungal-prophylaxis-with-posaconazole-tablet-in-paediatric-patients-after-haematopoietic-stem-cell-transplantation
#12
Michaela Döring, Karin Melanie Cabanillas Stanchi, Manon Queudeville, Judith Feucht, Franziska Blaeschke, Patrick Schlegel, Tobias Feuchtinger, Peter Lang, Ingo Müller, Rupert Handgretinger, Werner J Heinz
PURPOSE: Paediatric recipients of haematopoietic stem cell transplantation (HSCT) have a high risk for invasive fungal infections. Posaconazole oral suspension has proven to be effective in antifungal prophylaxis in adult and paediatric patients. A new posaconazole tablet formulation with absorption independent of the gastric conditions was approved by the FDA in 2013. This is the first report on the use of posaconazole tablets in paediatric patients. METHODS: This single-centre study included 63 paediatric patients with haemato-oncological malignancies who received posaconazole for antifungal prophylaxis after HSCT...
March 3, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28258218/structural-analyses-of-candida-albicans-sterol-14%C3%AE-demethylase-complexed-with-azole-drugs-address-the-molecular-basis-of-azole-mediated-inhibition-of-fungal-sterol-biosynthesis
#13
Tatiana Y Hargrove, Laura Friggeri, Zdzislaw Wawrzak, Aidong Qi, William J Hoekstra, Robert J Schotzinger, John D York, F Peter Guengerich, Galina I Lepesheva
With some advances in modern medicine (such as cancer chemotherapy, broad exposure to antibiotics, and immunosuppression) the incidence of opportunistic fungal pathogens such as Candida albicans has increased. Cases of drug resistance among these pathogens have become more frequent, requiring the development of new drugs and a better understanding of the targeted enzymes. Sterol 14α-demethylase (CYP51) is a cytochrome P450 enzyme required for biosynthesis of sterols in eukaryotic cells and the major target of clinical drugs for managing fungal pathogens, but some of the CYP51 key features important for rational drug design have remained obscure...
March 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28224698/determinants-of-the-magnitude-of-interaction-between-tacrolimus-and-voriconazole-posaconazole-in-solid-organ-recipients
#14
Thomas Vanhove, Hanneke Bouwsma, Luuk Hilbrands, Jesse J Swen, Isabel Spriet, Pieter Annaert, Bart Vanaudenaerde, Geert Verleden, Robin Vos, Dirk R J Kuypers
Administration of azole antifungals to tacrolimus-treated solid organ recipients results in a major drug-drug interaction characterized by increased exposure to tacrolimus. The magnitude of this interaction is highly variable but cannot currently be predicted. We performed a retrospective analysis of 126 solid organ recipients (95 lung, 31 kidney) co-treated with tacrolimus and voriconazole (n=100) or posaconazole (n=26). Predictors of the change in tacrolimus dose-corrected trough concentrations (C/D) between baseline and tacrolimus - azole co-therapy were assessed using linear mixed modeling...
February 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28223388/in-vitro-and-in-vivo-antifungal-profile-of-a-novel-and-long-acting-inhaled-azole-pc945-on-aspergillus-fumigatus-infection
#15
Thomas Colley, Alexandre Alanio, Steven L Kelly, Gurpreet Sehra, Yasuo Kizawa, Andrew G S Warrilow, Josie E Parker, Diane E Kelly, Genki Kimura, Lauren Anderson-Dring, Takahiro Nakaoki, Mihiro Sunose, Stuart Onions, Damien Crepin, Franz Lagasse, Matthew Crittall, Jonathan Shannon, Michael Cooke, Stéphane Bretagne, John King-Underwood, John Murray, Kazuhiro Ito, Pete Strong, Garth Rapeport
The profile of PC945, a novel triazole antifungal, designed for administration via inhalation, has been assessed in a range of in vitro and in vivo studies. PC945 was characterized as a potent, tight-binding inhibitor of Aspergillus fumigatus sterol 14α-demethylase (CYP51A and CYP51B) activity (IC50, 0.23 μM and 0.22 μM, respectively), with characteristic type II azole binding spectra. Against 96 clinically isolated A. fumigatus strains, the MIC values of PC945 ranged from 0.032∼>8 μg/ml, whilst those of voriconazole ranged from 0...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28217435/a-rare-fungal-infection-phaehyphomycosis-due-to-veronaea-botryosa-and-review-of-literature
#16
Anne Welfringer, Valérie Vuong, Nicolas Argy, Christian Chochillon, Lydia Deschamps, Guillaume Rollin, Stanislas Harent, Véronique Joly, William Vindrios, Vincent Descamps
We report a rare case of phaehyphomycosis in a 71-year-old heart transplant recipient Togo native patient. Four months after the transplant, he presented painless nodules on the right heel with superficial ulceration. The polyphasic identification uncovered a rare cause of phaehyphomycose: V. botryosa. The treatment combined surgical excision of the lesions and anti-fungal therapy with posaconazole. We discussed eleven reported cases in literature since 1990.
March 2017: Medical Mycology Case Reports
https://www.readbyqxmd.com/read/28207190/diaporthe-soft-tissue-infection-in-a-heart-transplant-patient
#17
Robert M Rakita, Kevin D O'Brien, Lori Bourassa
Infections caused by Diaporthe species are very uncommon. We describe a heart transplant recipient 14 years post transplant who developed a soft tissue fungal infection due to a Diaporthe species that responded well to surgical excision and posaconazole therapy. The Aspergillus galactomannan index was markedly elevated, and returned to normal following treatment. Solid organ transplant patients remain at risk of infection long after transplant and should be counseled about risk avoidance. This article is protected by copyright...
February 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28203579/rhabdomyolysis-following-initiation-of-posaconazole-use-for-antifungal-prophylaxis-in-a-patient-with-relapsed-acute-myeloid-leukemia-a-case-report
#18
Mayur D Mody, Deepak Ravindranathan, Harpaul S Gill, Vamsi K Kota
Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28196695/impact-of-erg3-mutations-and-expression-of-ergosterol-genes-controlled-by-upc2-and-ndt80-in-candida-parapsilosis-azole-resistance
#19
J Branco, M Ola, R M Silva, E Fonseca, N C Gomes, C Martins-Cruz, A P Silva, A Silva-Dias, C Pina-Vaz, C Erraught, L Brennan, A G Rodrigues, G Butler, I M Miranda
OBJECTIVES: Candida parapsilosis is a healthcare-related fungal pathogen particularly common among immunocompromised patients. Our understanding of antifungal resistance mechanisms in C. parapsilosis remains very limited. We previously described an azole-resistant strain of C. parapsilosis (BC014RPSC), obtained following exposure in vitro to posaconazole. Resistance was associated with overexpression of ergosterol biosynthetic genes (ERG genes), together with the transcription factors UPC2 (CPAR2-207280) and NDT80 (CPAR2-213640)...
February 11, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28191796/the-cost-of-treating-mucormycosis-with-isavuconazole-compared-with-standard-therapy-in-the-uk
#20
Emma Bagshaw, Daniel Kuessner, Jan Posthumus, Cesar Escrig, Michael Blackney, Sebastian Marcel Heimann, Oliver Andreas Cornely
AIM: Mucormycosis is a fungal infection associated with high mortality. Until recently, the only licensed treatments were amphotericin B (AMB) formulations. Isavuconazole (ISAV) is a new mucormycosis treatment. A UK-based economic model explored treatment costs with ISAV versus liposomal AMB followed by posaconazole. MATERIALS & METHODS: As a matched case-control analysis showed similar efficacy for ISAV and AMB, a cost-minimization approach was taken. Direct costs - drug acquisition, monitoring and administration, and hospitalization costs - were estimated from the National Health Service perspective...
February 13, 2017: Future Microbiology
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