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Posaconazole

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https://www.readbyqxmd.com/read/28087293/first-itraconazole-resistant-aspergillus-fumigatus-clinical-isolate-harbouring-a-g54e-substitution-in-cyp51ap-in-south-america
#1
Florencia Leonardelli, Laura Theill, María Elena Nardin, Daiana Macedo, Catiana Dudiuk, Emilce Mendez, Soledad Gamarra, Guillermo Garcia-Effron
BACKGROUND: A 27-year-old male rural worker was admitted with a fungal keratitis due to an injury involving plant detritus. MATERIALS AND METHODS: Specimens were collected for microscopy examination and culture. The isolate was identified by morphological and molecular criteria. Susceptibility testing was performed using CLSI methods. CYP51A gene was PCR amplified and sequenced. RESULTS: An Aspergillus fumigatus strain resistant to itraconazole (MIC>8μg/ml) was isolated...
January 10, 2017: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/28080986/clinical-implications-of-globally-emerging-azole-resistance-in-aspergillus-fumigatus
#2
REVIEW
Jacques F Meis, Anuradha Chowdhary, Johanna L Rhodes, Matthew C Fisher, Paul E Verweij
Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by Aspergillus However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of azole-based fungicides...
December 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28080217/synergistic-effects-of-tetrandrine-with-posaconazole-against-aspergillus-fumigatus
#3
Shui-Xiu Li, Yan-Jun Song, Ling Jiang, Ya-Jing Zhao, Hui Guo, Dong-Mei Li, Kun-Ju Zhu, Hong Zhang
In our earlier in vitro and in vivo studies, synergistic effects were observed when itraconazole or voriconazole were combined with tetrandrine (TET) against Aspergillus fumigatus, and the synergistic mechanism was related to inhibition of the drug efflux pump. Posaconazole (PCZ) is a broad-spectrum triazole antifungal agent used for the treatment of diverse fungal infections, including aspergillosis and candidiasis. Herein, the antifungal effects of TET are further investigated in vitro and in vivo alone or combined with PCZ against 20 clinical isolates of A...
January 12, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28053212/multilocus-phylogeny-and-antifungal-susceptibility-of-aspergillus-section-circumdati-from-clinical-samples-and-description-of-a-pseudosclerotiorum-sp-nov
#4
J P Z Siqueira, D A Sutton, J Gené, D García, N Wiederhold, S W Peterson, J Guarro
A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from Aspergillus section Circumdati from the USA, and to determine their in vitro antifungal susceptibility against eight antifungal drugs. The genetic markers used were ITS, BenA, CaM and RPB2, and the drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was A. westerdijkiae (29.4%), followed by a novel species, which was described here as A...
January 4, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28052853/activity-of-a-long-acting-echinocandin-cd101-and-seven-comparator-antifungal-agents-tested-against-a-global-collection-of-contemporary-invasive-fungal-isolates-in-the-sentry-2014-antifungal-surveillance-program
#5
Michael A Pfaller, Shawn A Messer, Paul R Rhomberg, Mariana Castanheira
The activity of CD101 and comparators was evaluated against 606 invasive fungal isolates collected worldwide during 2014 using the CLSI method. All C. albicans (n=251), C. tropicalis (n=51), C. krusei (n=16), and C. dubliniensis (n=11) were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or wild type to other echinocandins. Five C. glabrata (n=100) displayed CD101 MIC values of 1-4 μg/ml, elevated caspofungin (2->8 μg/ml), anidulafungin (2-4 μg/ml), and micafungin (2-4 μg/ml) MICs, and carried mutations on fks1/fks2 C...
January 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28045862/comparing-azole-plasma-trough-levels-in-lung-transplant-recipients-percentage-of-therapeutic-levels-and-intra-patient-variability
#6
Stelzer Daniela, Weber Alexandra, Ihle Franziska, Matthes Sandhya, Ceelen Felix, Zimmermann Gregor, Kneidinger Nikolaus, Schramm Rene, Winter Hauke, Zoller Michael, Vogeser Michael, Behr Juergen, Neurohr Claus
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, intra-patient variability for each azole was determined. METHODS: From July 2012 to July 2015, 806 APL of ITR, VOR, POS liquid (POS-Liq), and POS tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation (LTx) Program...
December 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28043787/-clusters-of-fusarium-solani-infection-in-juvenile-captive-born-caretta-caretta-sea-turtles
#7
M Garcia-Hartmann, C Hennequin, S Catteau, C Béatini, V Blanc
Various yeasts and filamentous fungi are described as the cause of infection in sea turtles. Among them, Fusarium solani is responsible both for superficial and invasive infection in weakened adults (capture, stranding), and wild nest contamination, causing massive losses during hatching. We illustrate the pathogenicity of this fungus in sea turtles, through our experience with the species Caretta caretta (loggerhead turtle) and its reproduction, which was obtained for the first time in 2010 at the marine park Marineland, Antibes and renewed in 2011 and 2013...
December 30, 2016: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28040568/in%C3%A2-vitro-drug-susceptibility-of-two-strains-of-the-wildlife-trypanosome-trypanosoma-copemani-a-comparison-with-trypanosoma-cruzi
#8
Adriana Botero, Sarah Keatley, Christopher Peacock, R C Andrew Thompson
Trypanosomes are blood protozoan parasites that are capable of producing illness in the vertebrate host. Within Australia, several native Trypanosoma species have been described infecting wildlife. However, only Trypanosoma copemani has been associated with pathological lesions in wildlife hosts and more recently has been associated with the drastic decline of the critically endangered woylie (Bettongia penicillata). The impact that some trypanosomes have on the health of the vertebrate host has led to the development of numerous drug compounds that could inhibit the growth or kill the parasite...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28031205/in-vitro-activity-of-posaconazole-against-talaromyces-marneffei-by-broth-microdilution-and-etest-methods-comparison-to-itraconazole-voriconazole-and-anidulafungin
#9
Susanna K P Lau, George C S Lo, Clare S K Lam, Wang-Ngai Chow, Antonio H Y Ngan, Alan K L Wu, Dominic N C Tsang, Cindy W S Tse, Tak-Lun Que, Bone S F Tang, Patrick C Y Woo
We determined the susceptibilities of 57 Talaromyces marneffei strains to anidulafungin, itraconazole, voriconazole and posaconazole, with MICs of 2-8, 0.002-0.004, 0.016-0.063 and 0.001-0.002 μg/ml by broth microdilution, and >32, ≤0.002-0.008, ≤0.002-0.008 and ≤0.002 μg/ml by Etest respectively at yeast phase; while MICs at mycelial phase for anidulafungin and posaconazole were 1-2 and 0.004-0.063 μg/ml respectively. The results suggest promising activities of posaconazole. Etest can be used for testing of azoles against T...
December 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28028453/identification-and-characterization-of-daldinia-eschscholtzii-isolated-from-skin-scrapings-nails-and-blood
#10
Kee Peng Ng, Chai Ling Chan, Su Mei Yew, Siok Koon Yeo, Yue Fen Toh, Hong Keat Looi, Shiang Ling Na, Kok Wei Lee, Wai-Yan Yee, Chee Sian Kuan
BACKGROUND: Daldinia eschscholtzii is a filamentous wood-inhabiting endophyte commonly found in woody plants. Here, we report the identification and characterization of nine D. eschscholtzii isolates from skin scrapings, nail clippings, and blood. METHODS: The nine isolates were identified based on colony morphology, light microscopy, and internal transcribed spacer (ITS)-based phylogeny. In vitro antifungal susceptibility of the fungal isolates was evaluated by the Etest to determine the minimum inhibitory concentration (MIC)...
2016: PeerJ
https://www.readbyqxmd.com/read/28019140/cutaneous-mucormycosis-as-result-of-insulin-administration-in-an-aml-patient-case-report-and-review-of-the-literature
#11
Anke Delie, Philip Vlummens, David Creytens, Eva Steel
We present a case of cutaneous mucormycosis in a patient with several important risk factors precipitating disease, namely underlying acute myeloid leukaemia and poorly controlled secondary diabetes. Inoculation was most likely caused by repeated minor trauma (insulin injection) at the site of infection. Treatment consisted of surgical debridement and liposomal Amphotericin B (LAmB) during 71 days. Posaconazole had already been initiated prior to infection as primary antifungal prophylaxis but was discontinued during follow-up as susceptibility testing later revealed resistance to posaconazole...
December 26, 2016: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28005452/preparation-and-evaluation-of-posaconazole-loaded-enteric-microparticles-in-rats
#12
Min Yang, Zhonghua Dong, Yongchun Zhang, Fang Zhang, Yongjie Wang, Zhongxi Zhao
Objectives Posaconazole (POS) is an antifungal compound which has a low oral bioavailability. The aim of this study was to prepare POS enteric microparticles to enhance its oral bioavailability. Methods POS enteric microparticles were prepared with hypromellose acetate succinate (HPMCAS) via the spray drying method. The solvent mixtures of acetone and ethanol used in the preparation of the microparticles were optimized to produce the ideal POS enteric microparticles. Multivariate data analysis using a principal component analysis was used to find the relationship among the HPMCAS molecular characteristics, particle properties and drug release kinetics from the spray dried microparticles...
December 22, 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28004589/an-update-on-the-safety-and-interactions-of-antifungal-drugs-in-stem-cell-transplant-recipients
#13
Corrado Girmenia, Anna Paola Iori
Invasive fungal diseases (IFDs) are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Improvement in the management of IFDs have been achieved with the availability of new effective and safe antifungal drugs, however, many of these newer treatments have some limitations in their variable toxicity and unique predisposition for pharmacokinetic drug-drug interactions. Areas covered: This article is an update of a previous review published in this journal evaluating the safety profile of the antifungal drugs...
December 26, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28002285/ochroconis-gallopava-endophthalmitis-successfully-treated-with-intravitreal-voriconazole-and-amphotericin-b
#14
Esther L Kim, Sachi R Patel, Meena S George, Hossein Ameri
PURPOSE: Ochroconis gallopava is a darkly pigmented septated fungus that rarely infects humans, almost universally immunocompromised individuals. Only one previous case has been reported of O. gallopava endophthalmitis, in which the patient progressed to a visual acuity of no light perception. The authors currently describe the first successfully treated case of O. gallopava endophthalmitis. METHODS: A 65-year-old Hispanic woman on chronic immunosuppression after a right lung transplant was admitted to the hospital for O...
December 20, 2016: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/27994475/isavuconazole-for-the-treatment-of-invasive-aspergillosis-and-mucormycosis-current-evidence-safety-efficacy-and-clinical-recommendations
#15
REVIEW
Suganthini Krishnan Natesan, Pranatharthi H Chandrasekar
The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA) and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles...
2016: Infection and Drug Resistance
https://www.readbyqxmd.com/read/27994139/triazoles-inhibit-cholesterol-export-from-lysosomes-by-binding-to-npc1
#16
Michael N Trinh, Feiran Lu, Xiaochun Li, Akash Das, Qiren Liang, Jef K De Brabander, Michael S Brown, Joseph L Goldstein
Niemann-Pick C1 (NPC1), a membrane protein of lysosomes, is required for the export of cholesterol derived from receptor-mediated endocytosis of LDL. Lysosomal cholesterol export is reportedly inhibited by itraconazole, a triazole that is used as an antifungal drug [Xu et al. (2010) Proc Natl Acad Sci USA 107:4764-4769]. Here we show that posaconazole, another triazole, also blocks cholesterol export from lysosomes. We prepared P-X, a photoactivatable cross-linking derivative of posaconazole. P-X cross-linked to NPC1 when added to intact cells...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27988409/cerebral-rhizomucor-infection-treated-by-posaconazole-delayed-release-tablets-in-an-allogeneic-stem-cell-transplant-recipient
#17
Diego O Andrey, Laurent Kaiser, Stéphane Emonet, Veronique Erard, Yves Chalandon, Christian van Delden
Mucormycosis (zygomycosis) is an emerging fungal disease in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. A 30-year-old woman diagnosed with acute myelomonocytic leukemia and needing allo-HSCT presented pulmonary and cerebral infection due to Rhizomucor pusillus. This fungal infection was treated with surgical treatment and posaconazole delayed-release tablets. This strategy allowed reaching high drug levels that could not be obtained with the posaconazole solution.
December 14, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27982447/therapeutic-drug-monitoring-of-posaconazole-oral-suspension-in-paediatric-patients-younger-than-13-years-of-age-a-retrospective-analysis-and-literature-review
#18
T Jancel, P A Shaw, C W Hallahan, T Kim, A F Freeman, S M Holland, S R Penzak
WHAT IS KNOWN AND OBJECTIVE: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD)...
February 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/27977554/neonatal-cutaneous-invasive-aspergillosis-accompanied-by-hemophagocytic-lymphohistocytosis
#19
Zhuanggui Chen, Lifen Yang, Yating Li, Li Pan, Meirong Li, Abdullah M S Al-Hatmi, Jacques F Meis, Wei Lai, Peiying Feng
We describe a 6-week-old female infant with cutaneous invasive aspergillosis accompanied with hemophagocytic lymphohistocytosis. Aspergillus flavus was isolated from biopsies of necrotic skin lesions on the forehead and scalp; morphologic identification was confirmed by molecular analysis. In vitro antifungal susceptibility testing showed that amphotericin B and triazoles had potent activity. The patient responded well to treatment with intravenous amphotericin B combined with oral posaconazole, and local wound care...
December 12, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27977118/rapid-chagas-disease-drug-target-discovery-using-directed-evolution-in-drug-sensitive-yeast
#20
Sabine Ottilie, Gregory M Goldgof, Claudia Magalhaes Calvet, Gareth K Jennings, Greg LaMonte, Jake Schenken, Edgar Vigil, Prianka Kumar, Laura-Isobel McCall, Eduardo Soares Constantino Lopes, Felicia Gunawan, Jennifer Yang, Yo Suzuki, Jair L Siqueira-Neto, James H McKerrow, Rommie E Amaro, Larissa M Podust, Jacob D Durrant, Elizabeth A Winzeler
Recent advances in cell-based, high-throughput phenotypic screening have identified new chemical compounds that are active against eukaryotic pathogens. A challenge to their future development lies in identifying these compounds' molecular targets and binding modes. In particular, subsequent structure-based chemical optimization and target-based screening require a detailed understanding of the binding event. Here, we use directed evolution and whole-genome sequencing of a drug-sensitive S. cerevisiae strain to identify the yeast ortholog of TcCyp51, lanosterol-14-alpha-demethylase (TcCyp51), as the target of MMV001239, a benzamide compound with activity against Trypanosoma cruzi, the etiological agent of Chagas disease...
December 23, 2016: ACS Chemical Biology
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