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Posaconazole

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https://www.readbyqxmd.com/read/29785613/neuroinfections-caused-by-fungi
#1
REVIEW
Katarzyna Góralska, Joanna Blaszkowska, Magdalena Dzikowiec
BACKGROUND: Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. METHODS: One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections"...
May 21, 2018: Infection
https://www.readbyqxmd.com/read/29784842/eucast-determination-of-olorofim-f901318-susceptibility-of-mould-species-method-validation-and-mics
#2
Karin Meinike Jørgensen, Karen M T Astvad, Rasmus Krøger Hare, Maiken Cavling Arendrup
Olorofim is a novel antifungal agent with in vitro activity against Aspergillus and some other moulds. Here we addressed technical aspects for EUCAST olorofim testing and generated contemporary MIC data.EUCAST E.Def 9.3.1 testing was performed comparing two plate preparation methods (serial-dilution in medium (serial-plates) versus pre-dilution in DMSO (ISO-plates)), two lots of olorofim, visual (visual-MIC) versus spectrophotometer (spec-MIC) reading and four polystyrene plates using 34-53 Aspergillus isolates from five genera...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29783739/sterol-composition-of-clinically-relevant-mucorales-and-changes-resulting-from-posaconazole-treatment
#3
Christoph Müller, Thomas Neugebauer, Patrizia Zill, Cornelia Lass-Flörl, Franz Bracher, Ulrike Binder
Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales ( Lichtheimia corymbifera , Lichtheimia ramosa , Mucor circinelloides , Rhizomucor pusillus , Rhizopus arrhizus , and Rhizopus microsporus ) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry...
May 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29778564/simultaneous-quantification-of-systemic-azoles-and-their-major-metabolites-in-human-serum-by-hplc-pda-role-of-azole-metabolic-rate
#4
Alicia Gomez-Lopez, Laura Alcazar-Fuoli, Leticia Bernal-Martínez
We describe the development and validation of a novel liquid chromatography assay (HPLC/PDA) for simultaneous quantification of voriconazole, itraconazole, and posaconazole, as well as some of their major metabolites, voriconazole N-oxide and hydroxy-itraconazole, in human serum. Analytes were detected using a PDA system that allows the characterization of the specific UV spectra of each compound. The assay exhibited linearity between 0.25-16 mg/L for all the compounds tested. The accuracy and within- and between-day precision of the assay were in acceptable ranges...
April 14, 2018: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29770723/the-impact-of-azole-antifungal-drugs-on-imatinib-metabolism-in-human-liver-microsomes
#5
Xingxian Luo, Taifeng Li, Ze Yu, Xuecai Xue, Haiyang Zhao, Na Li, Liping Ma, Changqing Yang, Lin Huanglin, Wangyu Feng
1. Imatinib is widely used for the treatment of hematologic malignancies. It is common that imatinib is clinically co-prescribed with azole antifungal agents since these patients are more prone to invasive antifungal infection. The present study was to investigate the effects of azole antifungal drugs, including ketoconazole, fluconazole, voriconazole, itraconazole and posaconazole on imatinib metabolism. 2. The main metabolites, 1-OH midazolam and N-desmethyl imatinib, were determined in the absence and in the presence of various levels of ketoconazole, fluconazole, voriconazole, itraconazole and posaconazole...
May 17, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29768642/-rhinocerebral-mucormycosis
#6
Anke Mertens, Christoph Arens, Doreen Barche, Laszlo Scheinpflug, Friedrich Gunther Scholz, Stefan Vielhaber, Cordula Scherlach, Uwe Tröger, Gernot Geginat, Jacqueline Färber
Mucormycosis is a rare but serious type of fungal infection, which can progress rapidly especially in immunsupressed patients.We report about a 47 year old female patient with ptosis on the left eye. The ophthalmological report offered no further pathologic findings. Diabetes mellitus was known and the blood sugar value was very high.A computed tomography of the paranasal sinuses showed a shadow in the ethmoid bone and in an additonally performed MRI-scan, an increase of orbital fat and an extension of the ocular muscle were visible...
May 16, 2018: Laryngo- Rhino- Otologie
https://www.readbyqxmd.com/read/29767615/relevance-of-antifungal-penetration-in-biofilm-associated-resistance-of-candida-albicans-and-non-albicans-candida-species
#7
Rachna Singh, Anjna Kumari, Karminder Kaur, Parul Sethi, Arunaloke Chakrabarti
The role of penetration limitation in Candida biofilm-associated antifungal resistance remains unclear. Most of the previous work has been done on Candida albicans, although non-albicans (NAC) species are also implicated in invasive candidiasis and the biofilm matrix has been shown to vary amongst different species. Only a few studies have evaluated clinical isolates. This study aimed to determine the relevance of penetration limitation in the antifungal resistance of biofilms formed by C. albicans and NAC clinical isolates, using an agar disk diffusion assay...
May 16, 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29760835/cutaneous-mucormycosis-following-a-bullous-pemphigoid-flare-in-a-chronic-lymphocytic-leukemia-patient-on-ibrutinib
#8
Matthew K Stein, Saradasri Karri, Jackson Reynolds, Jeff Owsley, Austin Wise, Mike G Martin, Fereshteh Zare
While the recent development of novel therapeutics in oncology, such as small molecule kinase inhibitors (SMKIs), has enabled our ability to target disease-specific molecular pathways, the prolonged impact of these agents on the immune system and infectious risk remains to be seen. We present a 68-year-old male with refractory chronic lymphocytic leukemia (CLL) on ibrutinib monotherapy for 3 years who developed extensive cutaneous mucormycosis following a severe bullous pemphigoid (BP) flare. He received amphotericin B for 4 weeks and was continued on posaconazole with resolution of his mucormycosis infection...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29756722/-use-of-posaconazole-in-children-experience-in-a-tertiary-pediatric-hospital
#9
María T Rosanova, Carla Voto, María S Mussini, Claudia Sarkis, Sandra Gómez, Norma Sberna, Susana Carnovale, Beatriz Caracciolo, Roberto Lede
There is limited information on the use of posaconazole in children. This retrospective and descriptive study was conducted to evaluate the clinical, microbiological characteristics and evolution of patients treated with posaconazole between August 2010 and March 2017. We included 16 children. Median age: 161 months (interquartile range -IQR- 69-173 m). All had underlying disease and a proven invasive fungal infection. The most frequent isolated were Mucor spp. and Aspergillus spp. The mean posaconazole dose was 600 mg/day (400-800 mg/day) and the median duration of treatment was 223 days (IQR 48-632)...
June 1, 2018: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/29754839/-retrospective-study-of-25-cases-of-pulmonary-mucormycosis-in-acute-leukaemia
#10
REVIEW
D Caillot, C Legouge, I Lafon, E Ferrant, P B Pagès, A Plocque, L Estivalet, S Valot, F Dalle, H Abou Hanna, M-L Chretien
INTRODUCTION: In acute leukaemia (AL), the occurrence of pulmonary mucormycosis (PM), the incidence of which is increasing, as a result of chemotherapy induced marrow aplasia, remains a life threatening complication. METHODS: Analysis of clinical, biological and thoracic CT characteristics of patients with PM developing during the treatment of AL between 2000 and 2015. Day 0 (D0) was defined as the day with first CT evidence of PM. RESULTS: Among 1193 patients, 25 cases of PM were recorded during 2099 episodes of bone marrow aplasia...
May 10, 2018: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/29749631/persistence-of-a-posaconazole-mediated-drug-drug-interaction-with-ranolazine-after-cessation-of-posaconazole-administration-impact-of-obesity-and-implications-for-patient-safety
#11
Christina R Chow, Jerold S Harmatz, Michael J Ryan, David J Greenblatt
The antianginal agent ranolazine (Ranexa®) is metabolized primarily by cytochrome P450-3A (CYP3A) enzymes. Coadministration with strong CYP3A inhibitors, such as ketoconazole and posaconazole, is contraindicated due to risk of QT prolongation from high levels of ranolazine. This study evaluated the time course of recovery from the posaconazole drug interaction in normal-weight and otherwise healthy obese subjects. Subjects received single doses of ranolazine in the baseline control condition, again during coadministration of posaconazole, and at 4 additional time points during the 2 weeks after posaconazole discontinuation...
May 11, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29746955/micafungin-versus-posaconazole-prophylaxis-in-acute-leukemia-or-myelodysplastic-syndrome-a-randomized-study
#12
David J Epstein, Susan K Seo, Yao-Ting Huang, Jay H Park, Virginia M Klimek, Ellin Berman, Martin S Tallman, Mark G Frattini, Genovefa A Papanicolaou
OBJECTIVES: To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS). METHODS: Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death)...
May 7, 2018: Journal of Infection
https://www.readbyqxmd.com/read/29735569/isavuconazole-concentration-in-real-world-practice-consistency-with-results-from-clinical-trials
#13
David Andes, Laura Kovanda, A Desai, Theresa Kitt, M Zhao, Thomas J Walsh
Clinical use of voriconazole, posaconazole, and itraconazole revealed the need for therapeutic drug monitoring (TDM) of plasma concentrations of these antifungal agents. This need for TDM was not evident from clinical trials of these drugs. In order to establish if this requirement also applies to isavuconazole, we examined the plasma concentrations of 283 samples receiving isavuconazole in clinical practice and compared the values to those from clinical trials. The concentration distributions from real-world use and clinical trials were nearly identical (>1 μg/mL in 90% of patients)...
May 7, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29725811/genetic-diversity-and-antifungal-susceptibility-of-candida-parapsilosis-sensu-stricto-isolated-from-bloodstream-infections-in-turkish-patients
#14
Süleyha Hilmioğlu-Polat, Somayeh Sharifynia, Yasemin Öz, Müge Aslan, Nuray Gündoğdu, Ayşe Serin, Haleh Rafati, Faezeh Mohammadi, Dilek Yeşim-Metin, Aylin Döğen, Macit Ilkit, Seyedmojtaba Seyedmousavi
Candida parapsilosis sensu stricto is an emerging cause of hospital-acquired Candida infections, predominantly in southern Europe, South America, and Asia. We investigated the genetic diversity and antifungal susceptibility profile of 170 independent C. parapsilosis sensu stricto strains obtained from patients with candidemia who were treated at the Ege University Hospital in Izmir, Turkey, between 2006 and 2014. The identity of each strain was confirmed via PCR amplification and digestion of the secondary alcohol dehydrogenase-encoding gene...
May 3, 2018: Mycopathologia
https://www.readbyqxmd.com/read/29712993/development-of-a-quantitative-pcr-detecting-cunninghamella-bertholletiae-to-help-in-diagnosing-this-rare-and-aggressive-mucormycosis
#15
Anne-Pauline Bellanger, Ana Berceanu, Steffi Rocchi, Benoit Valot, Jean Fontan, Adrien Chauchet, Nicolas Belin, Emeline Scherer, Eric Deconinck, Jean-Christophe Navellou, Laurence Millon
Mucormycosis is an invasive mold infection, frequently fatal in immunocompromised patients. We report the case of a patient with chronic lymphocytic leukemia admitted to the hematology unit for febrile aplasia. Pulmonary lesions suggesting a fungal infection expanded/increased despite a combination of posaconazole and liposomal amphotericin B. The fungal biomarkers performed repeatedly were negative. At D65 after chemotherapy a bronchial biopsy was positive for Cunninghamella bertholletiae. The patient died despite appropriate antifungal management...
April 30, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29712663/a-population-pharmacokinetic-model-for-a-solid-oral-tablet-formulation-of-posaconazole
#16
Marlou L P S van Iersel, Stefaan Rossenu, Rik de Greef, Hetty Waskin
A delayed-release solid tablet formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid tablet formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients...
April 30, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29702751/airway-persistence-by-the-emerging-multi-azole-resistant-rasamsonia-argillacea-complex-in-cystic-fibrosis
#17
Alireza Abdolrasouli, Amelia C Bercusson, Johanna L Rhodes, Ferry Hagen, Jochem B Buil, Alison Y Y Tang, Leonard L de Boer, Anand Shah, Andrew J Milburn, J Stuart Elborn, Andrew L Jones, Jacques F Meis, Matthew C Fisher, Silke Schelenz, Nicholas J Simmonds, Darius Armstrong-James
Infections caused by Rasamsonia argillacea complex have been reported in various clinical settings. Cystic fibrosis (CF) is one of the main underlying conditions. An observational cohort study of CF patients with Rasamsonia in respiratory samples was conducted. Eight isolates from six patients were identified as R. argillacea complex and tested for antifungal susceptibility. All isolates had high MICs to voriconazole and posaconazole and low MECs to echinocandins. Four patients experienced lung function decline in the year preceding first Rasamsonia isolation...
April 27, 2018: Mycoses
https://www.readbyqxmd.com/read/29679707/enhanced-delivery-of-fixed-dose-combination-of-synergistic-antichagasic-agents-posaconazole-benznidazole-based-on-amorphous-solid-dispersions
#18
Camila Bezerra Melo Figueirêdo, Daniela Nadvorny, Amanda Carla Quintas de Medeiros Vieira, Giovanna Christinne Rocha de Medeiros Schver, José Lamartine Soares Sobrinho, Pedro José Rolim Neto, Ping I Lee, Monica Felts de La Roca Soares
Posaconazole (PCZ) and benznidazole (BNZ) are known to show synergetic effect in treating the acute and chronic phases of Chagas disease, a neglected parasitic disease. However, as both compounds are poorly water soluble, the development of amorphous solid dispersions (ASDs) of a PCZ/BNZ fixed-dose combination in a water-soluble polymer becomes an attractive option to increase their apparent solubility and dissolution rate, potentially improving their oral bioavailability. The initial approach was to explore solvent evaporated solid dispertion (SD) systems for a PCZ/BNZ 50:50 (wt%) combination at several total drug loading levels (from SD with 10% to 50% drug loading) in water-soluble carriers, including polyvinylpyrrolidone (PVP K-30) and vinylpyrrolidone-vinyl acetate copolymer (PVPVA 64)...
April 18, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29679234/clinical-pharmacokinetics-and-dose-recommendations-for-posaconazole-in-infants-and-children
#19
Sophida Boonsathorn, Iek Cheng, Frank Kloprogge, Carlos Alonso, Charmion Lee, Bilyana Doncheva, John Booth, Robert Chiesa, Adam Irwin, Joseph F Standing
OBJECTIVES: The objectives of this study were to investigate the population pharmacokinetics of posaconazole in immunocompromised children, evaluate the influence of patient characteristics on posaconazole exposure and perform simulations to recommend optimal starting doses. METHODS: Posaconazole plasma concentrations from paediatric patients undergoing therapeutic drug monitoring were extracted from a tertiary paediatric hospital database. These were merged with covariates collected from electronic sources and case-note reviews...
April 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29676953/overinduction-of-the-cyp51a-gene-after-exposure-to-azole-antifungals-provides-a-first-clue-to-the-resistance-mechanism-in-the-fusarium-solani-species-complex
#20
Maurine D'Agostino, Thomas Lemmet, Claire Dufay, Amandine Luc, Jean Pol Frippiat, Marie Machouart, Anne Debourgogne
The genus Fusarium is largely represented in fungal infections, not only mostly in plants but also in humans. Fungi belonging to the Fusarium solani species complex (FSSC) are those that are most frequently isolated in invasive fusariosis and present elevated minimum inhibitory concentrations for the main antifungal drugs used in medicine. This study is the first to investigate the resistance mechanism in FSSC by monitoring CYP51A expression in the presence of azole antifungals. After exposure to voriconazole, an overinduction of CYP51A was observed irrespective of the concentration of antifungal used and the generation studied...
April 20, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
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