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https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28271239/phase-i-trial-to-investigate-the-effect-of-renal-impairment-on-isavuconazole-pharmacokinetics
#16
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)...
June 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
#17
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 subtropical 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 European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method...
May 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28264840/prophylaxis-with-isavuconazole-or-posaconazole-protects-immunosuppressed-mice-from-pulmonary-mucormycosis
#18
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 compared to placebo-treated mice...
May 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28204571/in-vitro-combination-therapy-with-isavuconazole-against-candida-spp
#19
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
#20
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
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