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Posaconazole

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https://www.readbyqxmd.com/read/28923874/agar-based-screening-for-azole-resistance-in-aspergillus-fumigatus-using-vipcheck%C3%A2-a-single-centre-evaluation
#1
J B Buil, H A L van der Lee, A J M M Rijs, J Zoll, J A M F Hovestadt, W J G Melchers, P E Verweij
Introduction Antifungal susceptibility testing is an essential tool for guiding therapy, although EUCAST and CLSI reference methods are often only available in specialized centres. We studied the performance of an agar-based screening method for the detection of azole resistance in Aspergillus fumigatus cultures.Methods The VIPcheck™ consists of four wells containing voriconazole, itraconazole, posaconazole or a growth control. Ninety-six A. fumigatus isolates were used. Thirty-three isolates harboured a known resistance mechanism: TR34/L98H (11 isolates); TR46/Y121F/T289A (6 isolates); TR53 (2 isolates) and fourteen isolates with other cyp51A-gene point mutations...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923863/synergistic-effects-of-tacrolimus-and-azoles-against-exophiala-dermatitidis
#2
Lujuan Gao, Yi Sun, Chengyan He, Tongxiang Zeng, Ming Li
In vitro interactions of tacrolimus, a calcineurin inhibitor, and azoles including itraconazole, voriconazole, and posaconazole against planktonic cells and biofilms of Exophiala dermatitidis were assessed via broth microdilution checkerboard technique. A total of 16 clinical isolates were studied. The results revealed favorable synergistic inhibitory activity between tacrolimus and itraconazole, voriconazole, or posaconazole against planktonic cells of E. dermatitidis However, limited synergism was observed against biofilms of E...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28922604/a-comparative-study-on-the-performance-of-inert-and-functionalized-spheres-coated-with-solid-dispersions-made-of-two-structurally-related-antifungal-drugs
#3
Naila A Mugheirbi, Peter O'Connell, Dolores R Serrano, Anne Marie Healy, Lynne S Taylor, Lidia Tajber
Fluid bed coating offers potential advantages as a formulation platform for amorphous solid dispersions (ASDs) of poorly soluble drugs, being a one-step manufacturing process which could reduce the risk of phase separation associated with multiple step manufacturing approaches. However, the impact of the physicochemical nature of carrier spheres on the properties and drug release from the ASDs has not been studied in detail. In this work, tartaric acid (TAP) and microcrystalline cellulose (CEL) spheres were chosen as examples of functional and inert beads, respectively...
September 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28903522/retrospective-analysis-of-posaconazole-suspension-dosing-strategies-in-a-pediatric-oncology-population-single-center-experience
#4
Sherry Mathew, Michelle L Kussin, Dazhi Liu, Melissa Pozotrigo, Brian Seyboth, Jennifer Thackray, Shirley Qiong Yan, Meier Hsu, Nina Cohen, Susan K Seo
Limited data on optimal posaconazole dosing strategies for pediatric patients exist. In this study, we found that the median initial dose in patients who achieved a posaconazole plasma concentration of 0.7 μg/mL was 22.8 mg/kg per day whereas the median initial dose in those who did not reach the target concentration was 15.8 mg/kg per day; this result suggests that higher initial doses might be warranted.
September 1, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28893246/voriconazole-and-posaconazole-therapeutic-drug-monitoring-a-retrospective-study
#5
Whitley M Yi, Kelly E Schoeppler, Jaclyn Jaeger, Scott W Mueller, Robert MacLaren, Douglas N Fish, Tyree H Kiser
BACKGROUND: Therapeutic drug monitoring (TDM) aims to minimize the clinical impact of posaconazole and voriconazole pharmacokinetic variability. However, its benefits on clinical outcomes are still being defined. Additionally, TDM data are limited for posaconazole IV and delayed-release tablet formulations among specific patient populations, including critically ill. The aim of this study was to determine the percentage of therapeutic posaconazole and voriconazole drug levels across all formulations in a real-world clinical setting and elucidate factors affecting attainment of target concentrations...
September 11, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28880124/efficacy-and-safety-of-posaconazole-in-hematopoietic-stem-cell-transplantation-patients-with-invasive-fungal-disease
#6
Sudong Zhang, Yi He, Erlie Jiang, Jialin Wei, Donglin Yang, Rongli Zhang, Weihua Zhai, Guixin Zhang, Zhao Wang, Lining Zhang, Li Liu, Mingzhe Han, Sizhou Feng
AIM: Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. This study reports real-world efficacy and safety of posaconazole (POS) in HSCT recipients with IFD. PATIENTS & METHODS: We performed a retrospective study to investigate the efficacy and safety of POS oral suspension in 45 HSCT patients with IFD from December 2013 to December 2016. RESULTS: The success rate at 12 weeks after POS treatment was 57...
September 7, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28872724/successful-treatment-of-bilateral-endogenous-fusarium-solani-endophthalmitis-in-a-patient-with-acute-lymphocytic-leukemia
#7
Ilaria Rizzello, Fausto Castagnetti, Pier Giorgio Toschi, Patrizia Bertaccini, Laura Primavera, Michela Paolucci, Luca Faccioli, Luca Spinardi, Russell E Lewis, Michele Cavo, Marta Stanzani
Fusarium spp. are an uncommon cause of fungemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy...
September 5, 2017: Mycoses
https://www.readbyqxmd.com/read/28872517/favorable-outcome-in-coccidioides-endophthalmitis-a-combined-medical-and-surgical-treatment-approach
#8
Jennifer J Ling, Derek J Bays, George R Thompson, Ala Moshiri, Mark J Mannis
PURPOSE: To describe a case of Coccidioides endophthalmitis that resulted in a favorable visual outcome after a combined medical and surgical approach. METHODS: A 33-year-old previously healthy woman was referred for evaluation of dyspnea and left-sided vision loss, which began 3 months before, after a trip to Nevada. She was found to have a pulmonary cavitary lesion and fluffy white material in the anterior chamber. An aqueous and vitreous paracentesis grew Coccidioides species...
August 31, 2017: Cornea
https://www.readbyqxmd.com/read/28867258/risk-factors-for-suboptimal-drug-concentration-of-posaconazole-oral-suspension-in-patients-with-hematologic-malignancy
#9
E J Kim, K-S Yu, S H Na, E Y Nam, H S Oh, M Kim, S H Yoon, J-O Lee, Y Koh, K-H Song, P G Choe, J-Y Cho, S H Song, E S Kim, H B Kim, S-M Bang, N J Kim, M-D Oh, I Kim, W B Park
Absorption of posaconazole oral suspension is influenced by several factors including diet, medications, and mucosal integrity. However, there are few prospective data about which is the most important modifiable factor in routine clinical practice. We prospectively analyzed clinical risk factors associated with low posaconazole trough concentrations in 114 patients receiving anticancer chemotherapy due to acute myeloid leukemia or myelodysplastic syndrome who received posaconazole oral suspension. In multivariate analyses, risk factors for drug level<500ng/mL included low calorie intake, mucositis≥grade 2, H2 blocker famotidine and proton-pump inhibitor...
August 31, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28864232/development-and-validation-of-a-liquid-chromatography-tandem-mass-spectrometry-assay-for-the-simultaneous-quantitation-of-5-azole-antifungals-and-1-active-metabolite
#10
Adam J McShane, Sihe Wang
BACKGROUND: Azole antifungal medications are often administered to prevent or treat invasive fungal infections. These infections are deadly in the immunocompromised population. Therapeutic drug monitoring of the azole antifungal medications may potentially decrease morbidity and mortality in patients undergoing azole treatment. METHODS: To assist with azole therapeutic drug monitoring, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for 6 azole analytes: fluconazole, voriconazole, posaconazole, isavuconazole, itraconazole, and its active metabolite hydroxyitraconazole...
August 31, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28836110/effects-of-photodynamic-therapy-on-the-growth-and-antifungal-susceptibility-of-scedosporium-and-lomentospora-spp
#11
Qiaoyun Lu, Yi Sun, Dingdan Tian, Shoubao Xiang, Lujuan Gao
Scedosporium and Lomentospora species are the second most frequent colonizing, allergenic, or invasive fungal pathogens in patients with cystic fibrosis, and are responsible for infections varying from cutaneous and subcutaneous tissue infections caused by traumatic inoculation to severe systemic diseases in immunocompromised patients. The clinical relevance of fungal airway colonization for individual patients harboring Scedosporium and Lomentospora species is still an underestimated issue. The high resistance of Scedosporium and Lomentospora species to antifungal drugs has highlighted the need for alternative treatment modalities, and antimicrobial photodynamic therapy may be one such alternative...
August 23, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28830945/pharmacodynamics-of-the-orotomides-against-aspergillus-fumigatus-new-opportunities-for-treatment-of-multidrug-resistant-fungal-disease
#12
William W Hope, Laura McEntee, Joanne Livermore, Sarah Whalley, Adam Johnson, Nicola Farrington, Ruwanthi Kolamunnage-Dona, Julie Schwartz, Anthony Kennedy, Derek Law, Michael Birch, John H Rex
F901318 is an antifungal agent with a novel mechanism of action and potent activity against Aspergillus spp. An understanding of the pharmacodynamics (PD) of F901318 is required for selection of effective regimens for study in phase II and III clinical trials. Neutropenic murine and rabbit models of invasive pulmonary aspergillosis were used. The primary PD endpoint was serum galactomannan. The relationships between drug exposure and the impacts of dose fractionation on galactomannan, survival, and histopathology were determined...
August 22, 2017: MBio
https://www.readbyqxmd.com/read/28817288/in-silico-modeling-approach-for-the-evaluation-of-gastrointestinal-dissolution-supersaturation-and-precipitation-of-posaconazole
#13
Bart Hens, Shriram M Pathak, Amitava Mitra, Nikunjkumar Patel, Bo Liu, Sanjaykumar Patel, Masoud Jamei, Joachim Brouwers, Patrick Augustijns, David B Turner
The aim of this study was to evaluate gastrointestinal (GI) dissolution, supersaturation, and precipitation of posaconazole, formulated as an acidified (pH 1.6) and neutral (pH 7.1) suspension. A physiologically-based pharmacokinetic (PBPK) modeling and simulation tool was applied to simulate GI and systemic concentration-time profiles of posaconazole which were directly compared with intraluminal and systemic data measured in humans. The Advanced Dissolution Absorption and Metabolism (ADAM) model of the Simcyp® Simulator correctly simulated incomplete gastric dissolution and saturated duodenal concentrations of posaconazole in the duodenal fluids following administration of the neutral suspension...
August 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28808915/cost-effectiveness-of-posaconazole-tablets-for-invasive-fungal-infections-prevention-in-acute-myelogenous-leukemia-or-myelodysplastic-syndrome-patients-in-spain
#14
Rafael Cámara, Irmina Gozalbo, Manuel Jurado, Jaime Sanz, Belén Aragón, Santiago Grau
INTRODUCTION: Posaconazole is superior to fluconazole (FLU) and itraconazole (ITRA) in the prevention of invasive fungal diseases (IFDs) in neutropenic patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). A new tablet formulation of posaconazole with improved pharmacokinetic and pharmacodynamic properties compared to posaconazole oral solution has recently been approved. The objective of this study is to estimate the cost-effectiveness of the newly developed posaconazole tablets versus FLU oral suspension or ITRA oral solution for preventing IFDs in high-risk neutropenic patients with AML or MDS and from the perspective of the Spanish National Health System (NHS)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28806568/a-simple-high-performance-liquid-chromatography-mass-spectrometry-method-for-therapeutic-drug-monitoring-of-isavuconazole-and-four-other-antifungal-drugs-in-human-plasma-samples
#15
Giovanna Fatiguso, Fabio Favata, Ilaria Zedda, Amedeo De Nicolò, Jessica Cusato, Valeria Avataneo, Giovanni Di Perri, Antonio D'Avolio
Triazoles chanced the prevention and treatment of invasive fungal infections, but their pharmacokinetic properties are still unclear. In particular, isavuconazole (ISC) is a new broad-spectrum antifungal triazole approved in 2015 as first-line treatment for intravenous and oral use against invasive aspergillosis and for mucormycosis. Nowadays, the optimal management of the treatments with triazoles requires the use of Therapeutic Drug Monitoring (TDM), in order to prevent sub-therapeutic or toxic concentrations...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28802855/antifungal-resistance-in-mucorales
#16
E Dannaoui
The order Mucorales, which includes the agents of mucormycosis, comprises a large number of species. These fungi are characterized by high-level resistance to most currently available antifungal drugs. Standardized antifungal susceptibility testing methods are now available, allowing a better understanding of the in vitro activity of antifungal drugs against members of Mucorales. Such tests have made apparent that antifungal susceptibility within this group may be species-specific. Experimental animal models of mucormycosis have also been developed and are of great importance in bridging the gap between in vitro results and clinical trials...
August 9, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28776447/analysis-of-imidazoles-and-triazoles-in-biological-samples-after-microextraction-by-packed-sorbent
#17
Cristina Campestre, Marcello Locatelli, Paolo Guglielmi, Elisa De Luca, Giuseppe Bellagamba, Sergio Menta, Gokhan Zengin, Christian Celia, Luisa Di Marzio, Simone Carradori
This paper reports the MEPS-HPLC-DAD method for the simultaneous determination of 12 azole drugs (bifonazole, butoconazole, clotrimazole, econazole, itraconazole, ketoconazole, miconazole, posaconazole, ravuconazole, terconazole, tioconazole and voriconazole) administered to treat different systemic and topical fungal infections, in biological samples. Azole drugs separation was performed in 36 min. The analytical method was validated in the ranges as follows: 0.02-5 μg mL(-1) for ravuconazole; 0.2-5 μg mL(-1) for terconazole; 0...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28768441/retrospective-analysis-of-goal-drug-level-attainment-of-posaconazole-for-invasive-fungal-infection-prophylaxis-in-patients-with-acute-myeloid-leukemia-pre-and-post-switch-to-tablet-formulation
#18
Tyler K Liebenstein, Kristin M Widmer, Michael J Fallon
Background Posaconazole is approved for invasive fungal infection prophylaxis in patients with hematologic malignancies. Posaconazole suspension is plagued by poor oral absorption and dietary requirements that are difficult for patients to meet. The delayed-release tablet formulation of posaconazole may be taken without regards to meals and has significantly better oral absorption than posaconazole suspension. Objectives We sought to determine if a switch to posaconazole tablets improved steady-state drug level attainment for invasive fungal infection prophylaxis in patients with acute myeloid leukemia...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28762740/in-situ-characterization-of-pharmaceutical-formulations-by-dynamic-nuclear-polarization-enhanced-mas-nmr
#19
Qing Zhe Ni, Fengyuan Yang, Thach V Can, Ivan V Sergeyev, Suzanne M D'Addio, Sudheer K Jawla, Yongjun Li, Maya P Lipert, Wei Xu, R Thomas Williamson, Anthony Leone, Robert G Griffin, Yongchao Su
A principal advantage of magic angle spinning (MAS) NMR spectroscopy lies in its ability to determine molecular structure in a noninvasive and quantitative manner. Accordingly, MAS should be widely applicable to studies of the structure of active pharmaceutical ingredients (API) and formulations. However, the low sensitivity encountered in spectroscopy of natural abundance APIs present at low concentration has limited the success of MAS experiments. Dynamic nuclear polarization (DNP) enhances NMR sensitivity and can be used to circumvent this problem provided that suitable paramagnetic polarizing agent can be incorporated into the system without altering the integrity of solid dosages...
August 31, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28760896/evaluation-of-posaconazole-serum-concentrations-from-delayed-release-tablets-in-patients-at-high-risk-for-fungal-infections
#20
Alan Chin, Steven A Pergam, David N Fredricks, Andrew N Hoofnagle, Kelsey K Baker, Rupali Jain
Purpose: To determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs), and to examine the effect of demographic traits and treatment characteristics on PCZ serum levelsMethods: A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that obtained PCZ for either treatment or prophylaxis from August 1(st) 2014 and August 31(st), 2015...
July 31, 2017: Antimicrobial Agents and Chemotherapy
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