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Isavuconazol

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https://www.readbyqxmd.com/read/28742650/reliable-and-easy-to-use-liquid-chromatography-tandem-mass-spectrometry-method-for-simultaneous-analysis-of-fluconazole-isavuconazole-itraconazole-hydroxy-itraconazole-posaconazole-and-voriconazole-in-human-plasma-and-serum
#1
Carsten Müller, David Gehlen, Cornelia Blaich, Domenik Prozeller, Blasius Liss, Thomas Streichert, Martin H J Wiesen
BACKGROUND: A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of six triazoles (fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), voriconazole (VRZ)) in human plasma and serum was developed and validated for therapeutic drug monitoring (TDM). METHODS: Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation...
July 24, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28722255/drug-drug-interactions-between-triazole-antifungal-agents-used-to-treat-invasive-aspergillosis-and-immunosuppressants-metabolized-by-cytochrome-p450-3a4
#2
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Robert J Brüggemann
Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus...
July 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28702763/pharmacokinetics-of-antifungal-drugs-practical-implications-for-optimized-treatment-of-patients
#3
REVIEW
Romuald Bellmann, Piotr Smuszkiewicz
INTRODUCTION: Because of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety. MATERIALS AND METHODS: This review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy. CONCLUSIONS AND DISCUSSION: Amphotericin B is eliminated unchanged via urine and faeces...
July 12, 2017: Infection
https://www.readbyqxmd.com/read/28696236/combination-therapy-with-isavuconazole-and-micafungin-for-treatment-of-experimental-invasive-pulmonary-aspergillosis
#4
Vidmantas Petraitis, Ruta Petraitiene, Matthew W McCarthy, Laura L Kovanda, Myo H Zaw, Kaiser Hussain, Naima Shaikh, Bo Bo W Maung, Navjot K Sekhon, William W Hope, Thomas J Walsh
Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in immunocompromised patients. We hypothesized that simultaneous inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1→3)-β-D-glucan in the cell wall, respectively, by the antifungal triazole isavuconazole and the echinocandin micafungin, may result in improved outcome in experimental IPA in persistently neutropenic rabbits. Treatment groups included isavuconazole (ISA) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg/kg/day, micafungin at 2 mg/kg/day (MFG2), or combinations of (ISA20+MFG2), (ISA40+MFG2), (ISA60+MFG2), and untreated rabbits (UC)...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28674051/effects-of-isavuconazole-on-the-plasma-concentrations-of-tacrolimus-among-solid-organ-transplant-patients
#5
Ryan M Rivosecchi, Cornelius J Clancy, Ryan K Shields, Christopher R Ensor, Michael A Shullo, Bonnie A Falcione, Raman Venkataramanan, M Hong Nguyen
We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, tacrolimus concentration/dose normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable inter-patient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly, but rather guided by therapeutic drug monitoring...
July 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#6
REVIEW
Ali S Omrani, Reem S Almaghrabi
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28605488/in-vitro-activity-of-the-novel-antifungal-compound-f901318-against-difficult-to-treat-aspergillus-isolates
#7
J B Buil, A J M M Rijs, J F Meis, M Birch, D Law, W J G Melchers, P E Verweij
Background: F901318 is a new antifungal agent with a novel mechanism of action with activity against Aspergillus species. We investigated the in vitro activity of F901318 against a collection of Aspergillus isolates. Methods: A total of 213 Aspergillus isolates were used in this study. A total of 143 Aspergillus fumigatus sensu stricto isolates were used, of which 133 were azole resistant [25 TR 34 /L98H; 25 TR 46 /Y121F/T289A; 33 A. fumigatus with cyp51A -associated point mutations (25 G54, 1 G432 and 7 M220); and 50 azole-resistant A...
June 10, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28595486/special-considerations-for-the-diagnosis-and-treatment-of-invasive-pulmonary-aspergillosis
#8
Matthew William McCarthy, Thomas J Walsh
The diagnosis and treatment of invasive pulmonary aspergillosis (IPA) are ongoing challenges in clinical practice. While important advances have recently been made, including enhanced diagnostic modalities as well as novel therapeutic and prophylactic options, more effective options are urgently needed as the population of immunocompromised patients continues to expand. Areas covered: In this paper, we review novel approaches to diagnosis of IPA, including multiplex PCR, Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry and provide a detailed review of the extended-spectrum triazole isavuconazole, which was approved in 2015 to treat IPA...
June 21, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28497121/implementation-of-isavuconazole-in-a-fluorescence-based-high-performance-liquid-chromatography-kit-allowing-simultaneous-detection-of-all-four-currently-licensed-mold-active-triazoles
#9
René Jørgensen, Siri Rytcher Andersen, Karen Marie Thyssen Astvad, Maiken Cavling Arendrup
Isavuconazole (ISZ) is a newly available broad-spectrum triazole agent recently approved for the treatment of both invasive aspergillosis and mucormycosis. The aim of this study was to develop a simple and reliable method for therapeutic drug monitoring (TDM) of ISZ in human plasma samples. The method involves using a kit from ChromSystems intended for TDM of itraconazole (ITZ), posaconazole (PSZ), and voriconazole (VRZ) in serum/plasma for sample preparation and high-performance liquid chromatography, using fluorescence detection with emission and excitation wavelengths set to 261 and 366 nm, respectively...
May 2017: MSphere
https://www.readbyqxmd.com/read/28491888/successful-treatment-of-allergic-bronchopulmonary-aspergillosis-with-isavuconazole-case-report-and-review-of-the-literature
#10
Samantha E Jacobs, Deborah Saez-Lacy, Walter Wynkoop, Thomas J Walsh
Isavuconazole is a new triazole that is approved for primary therapy of invasive aspergillosis. We provide the first report of a patient with allergic bronchopulmonary aspergillosis (ABPA) who was successfully treated with isavuconazole with marked improvement and minimal adverse effects. We further review the literature on antifungal management of ABPA.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28472247/pharmacodynamics-of-isavuconazole-for-invasive-mold-disease-role-of-galactomannan-for-real-time-monitoring-of-therapeutic-response
#11
Laura L Kovanda, Ruwanthi Kolamunnage-Dona, Michael Neely, Johan Maertens, Misun Lee, William W Hope
Background.: The ability to make early therapeutic decisions when treating invasive aspergillosis using changes in biomarkers as a surrogate for therapeutic response could significantly improve patient outcome. Methods.: Cox proportional hazards model and logistic regression were used to correlate early changes in galactomannan index (GMI) to mortality and overall response, respectively, from patients with positive baseline GMI (≥0.5) and serial GMI during treatment from a phase 3 clinical trial for the treatment of invasive mold disease...
June 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28434195/use-of-isavuconazole-in-a-patient-with-voriconazole-induced-qtc-prolongation
#12
Tracy P Trang, Alexandra M Hanretty, Charles Langelier, Katherine Yang
A 22-year-old woman with cystic fibrosis developed QTc-interval prolongation following lung transplantation in the setting of voriconazole therapy. After the discontinuation of voriconazole and initiation of isavuconazole, her QTc interval normalized. This case highlights the unique property of QTc interval shortening by isavuconazole among the triazole antifungals. This article is protected by copyright. All rights reserved.
April 23, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28416539/comparison-of-eucast-and-clsi-reference-microdilution-mics-of-eight-antifungal-compounds-for-candida-auris-and-associated-tentative-epidemiological-cutoff-values
#13
M C Arendrup, Anupam Prakash, Joseph Meletiadis, Cheshta Sharma, Anuradha Chowdhary
Candida auris is an emerging multidrug-resistant yeast. So far, all but two susceptibility testing studies have examined ≤50 isolates, mostly with the CLSI method. We investigated CLSI and EUCAST MICs for 123 C. auris isolates and eight antifungals and evaluated various methods for epidemiological cutoff (ECOFF) determinations. MICs (in milligrams per liter) were determined using CLSI method M27-A3, and the EUCAST E.Def 7.3. ANOVA analysis of variance with Bonferroni's multiple-comparison test and Pearson analysis were used on log2 MICs (significance at P values of <0...
June 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28373148/evaluation-of-the-in-vitro-activity-of-isavuconazole-and-comparator-voriconazole-against-2635-contemporary-clinical-candida-and-aspergillus-isolates
#14
K M T Astvad, R K Hare, M C Arendrup
OBJECTIVE: The in vitro activity of isavuconazole was determined for 1677 Candida and 958 Aspergillus isolates from 2012-2014 with voriconazole as comparator. METHODS: Aspergillus isolates were screened for resistance using azole-agar. Screening positive Aspergillus and all Candida isolates underwent EUCAST broth-microdilution testing. Isolates were categorised as wild-type (wt) or non-wt, adopting EUCAST ECOFFs (where available) or wt upper limits (wtULs; two 2-fold dilutions above the MIC50)...
March 31, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28372907/design-synthesis-and-in-vitro-evaluation-of-novel-antifungal-triazoles
#15
Fei Xie, Tingjunhong Ni, Jing Zhao, Lei Pang, Ran Li, Zhan Cai, Zichao Ding, Ting Wang, Shichong Yu, Yongsheng Jin, Dazhi Zhang, Yuanying Jiang
Twenty-nine novel triazole analogues of ravuconazole and isavuconazole were designed and synthesized. Most of the compounds exhibited potent in vitro antifungal activities against 8 fungal isolates. Especially, compounds a10, a13, and a14 exhibited superior or comparable antifungal activity to ravuconazole against all the tested fungi. Structure-activity relationship study indicated that replacing 4-cyanophenylthioazole moiety of ravuconazole with fluorophenylisoxazole resulted in novel antifungal triazoles with more effectiveness and a broader-spectrum...
March 23, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28355467/new-pharmacological-opportunities-for-the-treatment-of-invasive-mould-diseases
#16
Marie-Pierre Ledoux, Elise Toussaint, Julie Denis, Raoul Herbrecht
Recently, several randomized studies have been published that will shape treatment decisions in the prevention and management of invasive mould infections. Liposomal amphotericin B is an option for empirical or targeted treatment of invasive aspergillosis or mucormycosis, but for prophylaxis therapy, the triazole class now predominates. The triazole voriconazole is currently regarded as a drug of choice for the treatment of proven or probable invasive aspergillosis, and has shown significantly higher response rates than amphotericin B deoxycholate in this setting, with fewer severe drug-related adverse events...
March 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28355466/invasive-mould-infections-in-the-icu-setting-complexities-and-solutions
#17
REVIEW
Matteo Bassetti, Emilio Bouza
Infections caused by filamentous fungi represent a major burden in the ICU. Invasive aspergillosis is emerging in non-neutropenic individuals with predisposing conditions, e.g. corticosteroid treatment, chronic obstructive pulmonary disease, liver cirrhosis, solid organ cancer, HIV infection and transplantation. Diagnosis is challenging because the signs and symptoms are non-specific, and initiation of additional diagnostic examinations is often delayed because clinical suspicion is low. Isolation of an Aspergillus species from the respiratory tract in critically ill patients, and tests such as serum galactomannan, bronchoalveolar lavage 1-3-β-d-glucan and specific PCR should be interpreted with caution...
March 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28355463/therapeutic-drug-monitoring-for-invasive-mould-infections-and-disease-pharmacokinetic-and-pharmacodynamic-considerations
#18
REVIEW
Katharine E Stott, William W Hope
Therapeutic drug monitoring (TDM) may be required to achieve optimal clinical outcomes in the setting of significant pharmacokinetic variability, a situation that applies to a number of anti-mould therapies. The majority of patients receiving itraconazole should routinely be managed with TDM. Voriconazole exhibits highly variable inter-individual pharmacokinetics, and a trough concentration of 1.0-5.5 mg/L is widely accepted although it is derived from relatively low-quality evidence. The case for TDM of posaconazole is currently in a state of flux following the introduction of a newer tablet formulation with improved oral bioavailability, but it may be indicated when used for either prophylaxis or treatment of established disease...
March 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28355461/isavuconazole-is-there-a-need-for-a-new-antifungal
#19
Oliver A Cornely
No abstract text is available yet for this article.
March 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28289034/impact-of-mucositis-on-absorption-and-systemic-drug-exposure-of-isavuconazole
#20
Laura L Kovanda, Francisco M Marty, Johan Maertens, Amit V Desai, Christopher Lademacher, Marc Engelhardt, Qiaoyang Lu, William W Hope
Isavuconazonium sulfate is the water-soluble prodrug of isavuconazole. Population analyses have demonstrated relatively predictable pharmacokinetic (PK) behavior in diverse patient populations. We evaluated the impact of mucositis on the oral isavuconazole exposure using population PK modeling. This study included patients treated in two phase 3 trials of isavuconazole, SECURE for treatment of invasive aspergillosis (IA) and other filamentous fungi and VITAL for patients with mucormycosis, invasive fungal disease (IFD) caused by other rare fungi, or IA and renal impairment...
June 2017: Antimicrobial Agents and Chemotherapy
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