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Isavuconazole

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https://www.readbyqxmd.com/read/28434195/use-of-isavuconazole-in-a-patient-with-voriconazole-induced-qtc-prolongation
#1
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/candida-auris-comparison-of-the-eucast-and-clsi-reference-microdilution-mics-for-eight-antifungal-compounds-and-associated-tentative-ecoffs
#2
M C Arendrup, Anupam Prakash, Joseph Meletiadis, Cheshta Sharma, Anuradha Chowdhary
C. auris is an emerging multidrug-resistant yeast. So far, all but two susceptibility testing studies have examined ≤50 isolates and mostly with the CLSI method. We investigated CLSI and EUCAST MICs for 123 C. auris isolates and eight antifungals and evaluated various methods for ECOFF determination.MICs (mg/L) were determined using CLSI M27-A3 and EUCAST E.Def 7.3. ANOVA analysis with Bonferroni's multiple comparison test and Pearson analysis were used on log2MICs (significant, p<0.05). The percent agreement (±0->2 two-fold dilutions) between the methods was calculated...
April 17, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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/the-impact-of-mucositis-on-absorption-and-systemic-drug-exposure-of-isavuconazole
#9
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. METHODS: We evaluated 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...
March 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28271239/phase-i-trial-to-investigate-the-effect-of-renal-impairment-on-isavuconazole-pharmacokinetics
#10
Robert W Townsend, Shahzad Akhtar, Harry Alcorn, Jolene K Berg, Donna L Kowalski, Salim Mujais, Amit V Desai
PURPOSE: The purpose of the study is to evaluate the effect of renal impairment (RI) and end-stage renal disease (ESRD) on the pharmacokinetics (PK) of isavuconazole and the inactive cleavage product, BAL8728. METHODS: A single intravenous dose of the prodrug isavuconazonium sulfate (372 mg, equivalent to 200 mg isavuconazole and 75 mg of BAL8728 cleavage product) was administered to healthy controls (parts 1 and 2) and participants with mild, moderate, or severe RI (part 2) or ESRD (part 1); ESRD participants received two doses of 200 mg isavuconazole, 1 h post-dialysis (day 1) and prior to dialysis (day 15)...
March 7, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28264849/genetic-diversity-and-in-vitro-antifungal-susceptibility-of-200-clinical-and-environmental-aspergillus-flavus-isolates
#11
Mojtaba Taghizadeh-Armaki, Mohammad Taghi Hedayati, Saham Ansari, Saeed Mahdavi Omran, Sasan Saber, Haleh Rafati, Jan Zoll, Henrich A van der Lee, Willem J G Melchers, Paul E Verweij, Seyedmojtaba Seyedmousavi
Aspergillus flavus has been frequently reported as the leading cause of invasive aspergillosis in certain tropical and sub-tropical countries.Two hundred A. flavus strains originating from clinical and environmental sources and collected between 2008 and 2015 were phylogenetically identified at the species level by analyzing partial β-tubulin and calmodulin genes. In vitro antifungal susceptibility testing was performed against antifungals using the EUCAST (European Committee on Antimicrobial Susceptibility Testing) broth microdilution method...
March 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28264840/prophylaxis-with-isavuconazole-or-posaconazole-protect-immunosuppressed-mice-from-pulmonary-mucormycosis
#12
Teclegiorgis Gebremariam, Sondus Alkhazraji, Clara Baldin, Laura Kovanda, Nathan P Wiederhold, Ashraf S Ibrahim
We assessed prophylactic or continuous therapy of isavuconazole, posaconazole or voriconazole in treating pulmonary murine mucormycosis. In the prophylaxis studies, only isavuconazole treatment resulted in significantly improved survival and lowered tissue fungal burden of immunosuppressed mice infected with Rhizopus delemar. In the continuous treatment studies, isavuconazole and posaconazole, but not voriconazole, equally prolonged survival time and lowered tissue fungal burden versus placebo-treated mice...
March 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28204571/in-vitro-combination-therapy-with-isavuconazole-against-candida-spp
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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 hematologic 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...
March 2017: Haematologica
https://www.readbyqxmd.com/read/28004589/an-update-on-the-safety-and-interactions-of-antifungal-drugs-in-stem-cell-transplant-recipients
#20
REVIEW
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...
March 2017: Expert Opinion on Drug Safety
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