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Isavuconazol

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https://www.readbyqxmd.com/read/28204571/in-vitro-combination-therapy-with-isavuconazole-against-candida-spp
#1
Aspasia Katragkou, Matthew McCarthy, Joseph Meletiadis, Kaiser Hussain, Patriss W Moradi, Gittel E Strauss, Kyaw L Myint, Myo H Zaw, Laura L Kovanda, Ruta Petraitiene, Emmanuel Roilides, Thomas J Walsh, Vidmantas Petraitis
No abstract text is available yet for this article.
February 16, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28197306/potent-antifungal-synergy-of-phthalazinone-and-isoquinolones-with-azoles-against-candida-albicans
#2
Aaron D Mood, Ilandari Dewage Udara Anulal Premachandra, Stanley Hiew, Fuqiang Wang, Kevin A Scott, Nathan J Oldenhuis, Haoping Liu, David L Van Vranken
Four phthalazinones (CIDs 22334057, 22333974, 22334032, 22334012) and one isoquinolone (CID 5224943) were previously shown to be potent enhancers of antifungal activity of fluconazole against Candida albicans. Several even more potent analogues of these compounds were identified, some with EC50 as low as 1 nM, against C. albicans. The compounds exhibited pharmacological synergy (FIC < 0.5) with fluconazole. The compounds were also shown to enhance the antifungal activity of isavuconazole, a recently FDA approved azole antifungal...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28191796/the-cost-of-treating-mucormycosis-with-isavuconazole-compared-with-standard-therapy-in-the-uk
#3
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
https://www.readbyqxmd.com/read/28131025/an-ultra-performance-liquid-chromatography-tandem-mass-spectrometry-method-for-the-therapeutic-drug-monitoring-of-isavuconazole-and-seven-other-antifungal-compounds-in-plasma-samples
#4
Balthazar Toussaint, Fanny Lanternier, Christian Woloch, Denis Fournier, Manon Launay, Eliane Billaud, Eric Dannaoui, Olivier Lortholary, Vincent Jullien
A new analytical method was developed for the routine Therapeutic Drug Monitoring of 8 antifungals compounds in 50μL of plasma: isavuconazole (ISZ), voriconazole (VRZ), posaconazole (PSZ), fluconazole (FCZ), caspofungin (CSF), flucytosine (5FC), itraconazole (ITZ) and its metabolite OH-itraconazole (OH-ITZ). After adding 50μL of the internal standard, which consisted in a mixture of the deuterated isotopes of the quantified compounds, the sample treatment consisted in a simple protein precipitation with 400μL of acetonitrile...
January 23, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28080986/clinical-implications-of-globally-emerging-azole-resistance-in-aspergillus-fumigatus
#5
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/28074556/qt-interval-shortening-with-isavuconazole-in-vitro-and-in-vivo-effects-on-cardiac-repolarization
#6
J Keirns, A Desai, D Kowalski, C Lademacher, S Mujais, B Parker, M J Schneidkraut, R Townsend, T Wojtkowski, T Yamazaki, M Yen, P R Kowey
Effects of isavuconazole (active moiety of isavuconazonium sulfate) on cardiac ion channels in vitro and cardiac repolarization clinically were assessed in a Phase 1, randomized, double-blind study in healthy individuals who received isavuconazole (after 2-day loading dose), at therapeutic or supratherapeutic doses daily for 11 days, moxifloxacin (400 mg QD), or placebo. A post-hoc analysis of the Phase 3 SECURE trial assessed effects on cardiac safety. L-type Ca(2+) channels were most sensitive to inhibition by isavuconazole...
January 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28011902/ecil-6-guidelines-for-the-treatment-of-invasive-candidiasis-aspergillosis-and-mucormycosis-in-leukemia-and-hematopoietic-stem-cell-transplant-patients
#7
Frederic Tissot, Samir Agrawal, Livio Pagano, Georgios Petrikkos, Andreas H Groll, Anna Skiada, Cornelia Lass-Flörl, Thierry Calandra, Claudio Viscoli, Raoul Herbrecht
The European Conference on Infections in Leukemia (ECIL) provides recommendations for diagnostic strategies and prophylactic, pre-emptive or targeted therapy strategies for various types of infection in patients with hematological malignancies or hematopoietic stem cell transplantation recipients. Meetings are held every two years since 2005 and evidence-based recommendations are elaborated after evaluation of the literature and discussion among specialists of nearly all European countries. In this manuscript, the ECIL group presents the 2015-update of the recommendations for the targeted treatment of invasive candidiasis, aspergillosis and mucormycosis...
December 23, 2016: Haematologica
https://www.readbyqxmd.com/read/28004589/an-update-on-the-safety-and-interactions-of-antifungal-drugs-in-stem-cell-transplant-recipients
#8
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/27994475/isavuconazole-for-the-treatment-of-invasive-aspergillosis-and-mucormycosis-current-evidence-safety-efficacy-and-clinical-recommendations
#9
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/27970802/the-cost-of-treating-mucormycosis-with-isavuconazole-compared-with-liposomal-amphotericin-b-followed-by-posaconazole-in-the-united-kingdom-economic-evaluation-of-the-phase-iii-vital-study-and-fungiscope-matched-case-control-analysis
#10
D Kuessner, E Bagshaw, M Blackney, O A Cornely, S M Heimann, J Posthumus
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27913989/cost-effectiveness-analysis-of-isavuconazole-vs-voriconazole-as-first-line-treatment-for-invasive-aspergillosis
#11
Rachel Harrington, Edward Lee, Hongbo Yang, Jin Wei, Andrew Messali, Nkechi Azie, Eric Q Wu, James Spalding
INTRODUCTION: Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective...
January 2017: Advances in Therapy
https://www.readbyqxmd.com/read/27904738/recent-developments-in-the-management-of-invasive-fungal-infections-in-patients-with-oncohematological-diseases
#12
REVIEW
Markus Ruhnke, Stefan Schwartz
Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27821435/what-can-be-learned-from-recent-new-drug-applications-a-systematic-review-of-drug-interaction-data-for-drugs-approved-by-the-us-fda-in-2015
#13
Jingjing Yu, Zhu Zhou, Katie H Owens, Tasha K Ritchie, Isabelle Ragueneau-Majlessi
As a follow up to previous reviews, the aim of the present analysis was to systematically examine all drug metabolism, transport, pharmacokinetics (PK), and drug-drug interaction (DDI) data available in the 33 new drug applications (NDAs) approved by the Food and Drug Administration (FDA) in 2015, using the University of Washington Drug Interaction Database, and to highlight the significant findings. In vitro, a majority of the new molecular entities (NMEs) were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter...
January 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27799223/evaluation-of-mic-strip-isavuconazole-test-for-susceptibility-testing-of-wild-type-and-non-wild-type-aspergillus-fumigatus-isolates
#14
Maiken Cavling Arendrup, Paul Verweij, Henrik Vedel Nielsen
We evaluated the MIC Strip Isavuconazole test against EUCAST E.Def 9.3 by using 40 wild-type and 39 CYP51A mutant Aspergillus fumigatus strains. The strip full inhibition endpoint (FIE) and 80% growth inhibition endpoint were determined by two independent readers, reader 1 (R1) and R2. The essential (within ±0, ±1, and ±2 twofold dilutions) and categorical agreements were best with the FIE (for R1/R2, 42%/41%, 75%/73%, and 90%/89% for essential agreement, and 91.1%/92.4% categorical agreement, with 6.3/8...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27798213/monotherapy-or-combination-therapy-of-isavuconazole-and-micafungin-for-treating-murine-mucormycosis
#15
Teclegiorgis Gebremariam, Nathan P Wiederhold, Abdullah Alqarihi, Priya Uppuluri, Nkechi Azie, John E Edwards, Ashraf S Ibrahim
OBJECTIVES: Previously we demonstrated the benefit of isavuconazole in treating murine mucormycosis due to Rhizopus. We wanted to determine the efficacy of isavuconazole in treating murine mucormycosis caused by Mucor, the second most common cause of the disease. Furthermore, because we previously determined that Rhizopus possesses the target enzyme for echinocandins and micafungin has activity against murine mucormycosis, we compared the activity of combination therapy (isavuconazole + micafungin) with placebo, either drug alone or standard therapy of liposomal amphotericin B (LAmB) in treating pulmonary murine mucormycosis caused by Rhizopus delemar...
October 24, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27793736/spectrophotometric-reading-of-eucast-antifungal-susceptibility-testing-of-aspergillus-fumigatus
#16
J Meletiadis, K Leth Mortensen, P E Verweij, J W Mouton, M C Arendrup
OBJECTIVES: Given the increasing number of antifungal drugs and the emergence of resistant Aspergillus isolates, objective, automated and high-throughput antifungal susceptibility testing is important. The EUCAST E.Def 9.3 reference method for MIC determination of Aspergillus species relies on visual reading. Spectrophotometric reading was not adopted because of concern that non-uniform filamentous growth might lead to unreliable and non-reproducible results. We therefore evaluated spectrophotometric reading for the determination of MICs of antifungal azoles against Aspergillus fumigatus...
February 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27781311/phellinus-species-an-emerging-cause-of-refractory-fungal-infections-in-patients-with-x-linked-chronic-granulomatous-disease
#17
REVIEW
Ghady Haidar, Christa S Zerbe, Michelle Cheng, Adrian M Zelazny, Steven M Holland, Kathleen R Sheridan
Aspergillus spp. are a leading cause of mortality in chronic granulomatous disease (CGD), but other fungi have emerged in the era of mould prophylaxis. Of these, Phellinus spp. are an under-recognised cause of invasive fungal infections (IFIs) in CGD, and data on their presentation and management are scarce. We present a patient with CGD who developed disseminated IFI involving the lungs and brain. Surgical specimens grew a basidiomycete which was disregarded as a contaminant. After three months of progressive disease despite antifungals, he was diagnosed with Phellinus tropicalis by internal transcribed spacer (ITS) sequencing...
October 26, 2016: Mycoses
https://www.readbyqxmd.com/read/27766566/isavuconazole-a-review-in-invasive-aspergillosis-and-mucormycosis
#18
Matt Shirley, Lesley J Scott
Isavuconazole is a second-generation triazole with activity against a broad spectrum of clinically important fungi. Its water-soluble prodrug, isavuconazonium sulfate (Cresemba(®)), available in interchangeable intravenous and oral formulations, is approved in the USA and EU for the treatment of adults with invasive aspergillosis and mucormycosis. In international phase III clinical trials, isavuconazole was efficacious and generally well tolerated in the treatment of these life-threatening diseases. In the phase III SECURE trial, isavuconazole was non-inferior to voriconazole for the primary treatment of invasive mould disease (primarily aspergillosis) and was associated with fewer drug-related treatment-emergent adverse events (TEAEs) than voriconazole...
November 2016: Drugs
https://www.readbyqxmd.com/read/27708619/epidemiological-and-genomic-landscape-of-azole-resistance-mechanisms-in-aspergillus-fungi
#19
Daisuke Hagiwara, Akira Watanabe, Katsuhiko Kamei, Gustavo H Goldman
Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic fungus Aspergillus. The predominant causal species is Aspergillus fumigatus, and azole drugs are the treatment of choice. Azole drugs approved for clinical use include itraconazole, voriconazole, posaconazole, and the recently added isavuconazole. However, epidemiological research has indicated that the prevalence of azole-resistant A. fumigatus isolates has increased significantly over the last decade. What is worse is that azole-resistant strains are likely to have emerged not only in response to long-term drug treatment but also because of exposure to azole fungicides in the environment...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27648202/antifungal-therapy-in-hematopoietic-stem-cell-transplant-recipients
#20
REVIEW
Alessandro Busca, Livio Pagano
Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan...
2016: Mediterranean Journal of Hematology and Infectious Diseases
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