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Katarzyna Góralska, Joanna Blaszkowska, Magdalena Dzikowiec
BACKGROUND: Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. METHODS: One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections"...
May 21, 2018: Infection
Julian Hösl, André Gessner, Nahed El-Najjar
A simple and precise ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous analysis of five anti-infective agents used to treat severe infections [three antibiotics (daptomycin, moxifloxacin, ciprofloxacin) and two antifungals (isavuconazole, caspofungin)] in human plasma. Sample preparation was based on protein precipitation with ice cold methanol. All five agents were analyzed with the corresponding isotopically labeled internal standards. All analytes were detected in multiple reactions monitoring (MRM) using API 4000 triple-quadrupole mass spectrometer with electrospray (ESI) source operating in positive mode...
May 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
Caitlin R Rausch, Adam J DiPippo, Prithviraj Bose, Dimitrios P Kontoyiannis
Isavuconazole (ISA) is increasingly used in leukemia patients. We retrospectively assessed breakthrough invasive fungal infections (b-IFIs) in 100 consecutive leukemia patients receiving ISA as single agent; 13 developed documented b-IFIs. (6 candidiasis, 6 mold infections, 4 mucormycosis). All b-IFIs were observed in patients with prolonged neutropenia and active leukemia.
May 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Xiaowei Zheng, Gaoqi Xu, Liqin Zhu, Luo Fang, Yiwen Zhang, Haiying Ding, Yinghui Tong, Jiao Sun, Ping Huang
The aim of this pharmacokinetic/pharmacodynamic (PK/PD) study is to evaluate the efficacy of various isavuconazole dosing regimens for healthy individuals and patients with hepatic or renal impairment against Aspergillus spp. and Candida spp. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamics (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (AUC/MIC) targets of isavuconazole...
May 15, 2018: Journal of Clinical Pharmacology
Roopam Jariwal, Arash Heidari, Ahana Sandhu, Janushe Patel, Kamelia Shoaepour, Piruthiviraj Natarajan, Everardo Cobos
Invasive fungal infections are commonly associated with some form of immunosuppression. On the nasal epithelial surface, Aspergillus flavus , under favorable conditions, can aggressively breach multiple cell lines invading the local tissues. We present the case of a 35-year-old woman with granulomatous invasive Aspergillus flavus infection involving the nasal sinuses and the brain. Antifungal agents administered in the previous episodes contained the infection; however, the infected site evolved over time surrounded with calcified tissues in the left maxillary sinus...
January 2018: Journal of Investigative Medicine High Impact Case Reports
Valeria Cozzi, Sara Baldelli, Simone Castoldi, Emilio Clementi, Dario Cattaneo
No abstract text is available yet for this article.
April 30, 2018: Therapeutic Drug Monitoring
Jeffrey D Jenks, Helmut Jf Salzer, Juergen Prattes, Robert Krause, Dieter Buchheidt, Martin Hoenigl
In recent decades, important advances have been made in the diagnosis and treatment of invasive aspergillosis (IA) and mucormycosis. One of these advances has been the introduction of isavuconazole, a second-generation broad spectrum triazole with a favorable pharmacokinetic and safety profile and few drug-drug interactions. Phase III trials in patients with IA and mucormycosis demonstrated that isavuconazole has similar efficacy to voriconazole for the treatment of IA (SECURE trial) and liposomal amphotericin B for the treatment of mucormycosis (VITAL trial with subsequent case-control analysis) and a favorable safety profile with significantly fewer ocular, hepatobiliary, and skin and soft tissue adverse events compared to voriconazole...
2018: Drug Design, Development and Therapy
Kiran Gajurel, Reshika Dhakal, Stan Deresinski
PURPOSE OF REVIEW: Unlike immunocompetent hosts, solid organ transplant (SOT) recipients with posttransplant histoplasmosis (PTH) often present with disseminated disease and have an attributable mortality of approximately 10%. In this review, we discuss currently available diagnostic tests and treatment strategies in PTH. RECENT FINDINGS: None of the available tests have a 100% diagnostic accuracy. Histoplasma antigen assays are the most sensitive commercially available tests...
May 5, 2018: Current Opinion in Infectious Diseases
David Andes, Laura Kovanda, A Desai, Theresa Kitt, M Zhao, Thomas J Walsh
Clinical use of voriconazole, posaconazole, and itraconazole revealed the need for therapeutic drug monitoring (TDM) of plasma concentrations of these antifungal agents. This need for TDM was not evident from clinical trials of these drugs. In order to establish if this requirement also applies to isavuconazole, we examined the plasma concentrations of 283 samples receiving isavuconazole in clinical practice and compared the values to those from clinical trials. The concentration distributions from real-world use and clinical trials were nearly identical (>1 μg/mL in 90% of patients)...
May 7, 2018: Antimicrobial Agents and Chemotherapy
Michael A Pfaller, Paul R Rhomberg, Mariana Castanheira
Isavuconazonium sulfate is a prodrug of isavuconazole, a broad-spectrum mould-active triazole antifungal drug. We provide a direct comparison of the in vitro activity of the prodrug versus the active metabolite against clinical isolates of Aspergillus spp., Sarocladium kiliense, and Scedosporium apiospermum using CLSI broth microdilution methods. The MIC values obtained for the prodrug were one 2-fold dilution higher than those of isavuconazole for all isolates tested. Using previously defined epidemiological cutoff values for isavuconazole and Aspergillus spp...
April 13, 2018: Diagnostic Microbiology and Infectious Disease
Matthew W McCarthy, Brad Moriyama, Ruta Petraitiene, Thomas J Walsh, Vidmantas Petraitis
In March 2015, the extended-spectrum triazole antifungal isavuconazole was granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. Isavuconaozle has activity against a broad range of yeasts, dimorphic fungi, and molds and is associated with fewer toxicities than voriconazole. It also has predictable pharmacokinetics in adults, fewer drug-drug interactions than many existing antifungal agents, and is available in both oral and β-cyclodextrin-free intravenous formulations...
May 4, 2018: Clinical Pharmacokinetics
Andrej Spec, Patricia Connolly, Rocio Montejano, L Joseph Wheat
No abstract text is available yet for this article.
April 12, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Monica Fung, Brian S Schwartz, Sarah B Doernberg, Charles Langelier, Mimi Lo, Larissa Graff, Marisela Tan, Aaron C Logan, Peter Chin-Hong, Jennifer M Babik
No abstract text is available yet for this article.
March 31, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Oliver A Cornely, Kathleen M Mullane, Luis Ostrosky-Zeichner, Rochelle M Maher, Rodney Croos-Dabrera, Qiaoyang Lu, Christopher Lademacher, John R Perfect, Ilana Oren, Anne-Hortense Schmitt-Hoffmann, Michael Giladi, Francisco M Marty, Galia Rahav
BACKGROUND: Data regarding treatment of rare invasive fungal diseases (IFDs) are scarce. OBJECTIVES: To document the efficacy and safety of isavuconazole for treatment of uncommonly diagnosed IFDs. PATIENTS/METHODS: VITAL was a single-arm, international, open-label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily). The primary outcome was overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety...
April 3, 2018: Mycoses
Francisco M Marty, Oliver A Cornely, Kathleen M Mullane, Luis Ostrosky-Zeichner, Rochelle M Maher, Rodney Croos-Dabrera, Qiaoyang Lu, Christopher Lademacher, Ilana Oren, Anne-Hortense Schmitt-Hoffmann, Michael Giladi, Galia Rahav, John R Perfect
BACKGROUND: The optimal approach to treat invasive fungal disease (IFD) caused by more than one fungal species is unknown. OBJECTIVES: To document the efficacy and safety of isavuconazole for treatment of IFDs caused by more than one fungal species. PATIENTS/METHODS: VITAL was a single-arm, international, open-label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily) for treatment of rare IFDs...
April 3, 2018: Mycoses
M Ghannoum, L Long, E L Larkin, N Isham, R Sherif, K Borroto-Esoda, S Barat, D Angulo
Invasive aspergillosis remains a major cause of death among the immunocompromised population and those receiving long-term immunosuppressive therapy. In light of increased azole resistance, variable outcomes with existing echinocandin mono and combination therapy, and persistent high mortality rates, new antifungal agents for the treatment of invasive aspergillosis are clearly needed.SCY-078 is the first in class triterpenoid antifungal, a novel class of glucan synthase inhibitors, with broad in vitro and in vivo activity against a broad spectrum of Candida and Aspergillus In vitro testing of clinical strains of Aspergillus fumigatus and non- fumigatus strains showed potent fungistatic activity of SCY-078 (minimum effective concentration, MEC90 = 0...
April 2, 2018: Antimicrobial Agents and Chemotherapy
J Król, U Nawrot, M Bartoszewicz
BACKGROUND: The antifungal activity of some popular analgesic drugs was postulated by several authors. OBJECTIVES: The aim of this study was to verify the antifungal effectiveness of acetylsalicylic acid, ibuprofen, metamizole, meloxicam and paracetamol against triazole-susceptible and triazole-resistant Candida spp isolates. METHODS: The minimal inhibitory concentration as well as fractional inhibitory concentration of selected analgesics and triazole on eighteen Candida spp isolates were determined by the standard microdilution method according to EUCAST...
March 28, 2018: Journal de Mycologie Médicale
Jingjing Yu, Zhu Zhou, Jessica Tay-Sontheimer, Rene H Levy, Isabelle Ragueneau-Majlessi
A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions...
March 23, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
John R Perfect, Oliver A Cornely, Markus Heep, Luis Ostrosky-Zeichner, Kathleen M Mullane, Rochelle Maher, Rodney Croos-Dabrera, Christopher Lademacher, Marc Engelhardt, Caroline Chen, Francisco M Marty
Invasive fungal disease (IFD) confers a substantial risk for morbidity and mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most common IFD caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for IA, but evidence to support efficacy and safety of antifungal agents for rare IFDs, or for IFDs in special patient populations, is limited or lacking. The VITAL trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with IA and renal impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi...
March 23, 2018: Mycoses
Eris Tollkuci
Midostaurin is the first approved FMS-related tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 mutated acute myeloid leukemia. Midostaurin is a major cytochrome P450 3A4 (CYP3A4) substrate. Coadministration with a strong CYP3A4 inhibitor or inducer can lead to a potential increase or decrease in midostaurin exposure. This report describes a 43-year-old patient with FLT3-internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia who initially presented with leukocytosis and concern for acute leukemia...
January 1, 2018: Journal of Oncology Pharmacy Practice
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