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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
Peter G Pappas, Michail S Lionakis, Maiken Cavling Arendrup, Luis Ostrosky-Zeichner, Bart Jan Kullberg
Invasive candidiasis is an important health-care-associated fungal infection that can be caused by several Candida spp.; the most common species is Candida albicans, but the prevalence of these organisms varies considerably depending on geographical location. The spectrum of disease of invasive candidiasis ranges from minimally symptomatic candidaemia to fulminant sepsis with an associated mortality exceeding 70%. Candida spp. are common commensal organisms in the skin and gut microbiota, and disruptions in the cutaneous and gastrointestinal barriers (for example, owing to gastrointestinal perforation) promote invasive disease...
May 11, 2018: Nature Reviews. Disease Primers
Subramanian Swaminathan, Shweta Kamat, Nalini Adele Pinto
The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting. However, apart from bacterial infections rising in hospitals, the incidences of fungal infections are growing with the development of resistance to conventional antifungal agents. Newer antifungal agents such as echinocandins (ECs) have been extensively studied over the past decade and are recognised as a superior treatment compared with prior antifungals as a first line of therapy in tertiary institutions...
January 2018: Indian Journal of Medical Microbiology
Süleyha Hilmioğlu-Polat, Somayeh Sharifynia, Yasemin Öz, Müge Aslan, Nuray Gündoğdu, Ayşe Serin, Haleh Rafati, Faezeh Mohammadi, Dilek Yeşim-Metin, Aylin Döğen, Macit Ilkit, Seyedmojtaba Seyedmousavi
Candida parapsilosis sensu stricto is an emerging cause of hospital-acquired Candida infections, predominantly in southern Europe, South America, and Asia. We investigated the genetic diversity and antifungal susceptibility profile of 170 independent C. parapsilosis sensu stricto strains obtained from patients with candidemia who were treated at the Ege University Hospital in Izmir, Turkey, between 2006 and 2014. The identity of each strain was confirmed via PCR amplification and digestion of the secondary alcohol dehydrogenase-encoding gene...
May 3, 2018: Mycopathologia
María Ángeles Bordallo-Cardona, Laura Judith Marcos-Zambrano, Carlos Sánchez-Carrillo, Emilio Bouza, Patricia Muñoz, Pilar Escribano, Jesús Guinea
Background: We examined the rapid evaluation of susceptibility to echinocandins in Candida spp. using the Etest performed directly on positive blood cultures and anidulafungin-containing agar plates. Methods: We prospectively collected 80 positive blood cultures (Bactec™-FX system, Becton-Dickinson, Cockeysville, Maryland, USA) with echinocandin-susceptible Candida spp (n=60) and echinocandin-intermediate C. parapsilosis (n=20) from patients with candidemia. Additionally, blood culture bottles of nonfungemic/bacteremic patients were spiked with 35 echinocandin-resistant Candida spp...
April 30, 2018: Antimicrobial Agents and Chemotherapy
Alireza Abdolrasouli, Amelia C Bercusson, Johanna L Rhodes, Ferry Hagen, Jochem B Buil, Alison Y Y Tang, Leonard L de Boer, Anand Shah, Andrew J Milburn, J Stuart Elborn, Andrew L Jones, Jacques F Meis, Matthew C Fisher, Silke Schelenz, Nicholas J Simmonds, Darius Armstrong-James
Infections caused by Rasamsonia argillacea complex have been reported in various clinical settings. Cystic fibrosis (CF) is one of the main underlying conditions. An observational cohort study of CF patients with Rasamsonia in respiratory samples was conducted. Eight isolates from six patients were identified as R. argillacea complex and tested for antifungal susceptibility. All isolates had high MICs to voriconazole and posaconazole and low MECs to echinocandins. Four patients experienced lung function decline in the year preceding first Rasamsonia isolation...
April 27, 2018: Mycoses
Ruben Ramos, Diego H Caceres, Marilyn Perez, Nicole Garcia, Wendy Castillo, Erika Santiago, Jovanna Borace, Shawn R Lockhart, Elizabeth L Berkow, Lizbeth Hayer, Andres Espinosa-Bode, Jose Moreno, Brendan R Jackson, Jackeline Moran, Tom Chiller, Gloriela de Villarreal, Nestor Sosa, Snigdha Vallabhaneni
Candida duobushaemulonii , a yeast closely related to Candida auris, is thought to rarely cause infections, and is often misidentified. In October 2016, the Panamanian Ministry of Health implemented laboratory surveillance for C. auris Suspected C. auris isolates were forwarded to the national reference laboratory for identification by Matrix Assisted Laser Desorption Ionization-Time of Flight mass spectrometry and antifungal susceptibility testing. During November 2016-May 2017, 17 of 36 (47%) isolates suspected to be C...
April 25, 2018: Journal of Clinical Microbiology
Amy Carr, Peter Colley, Mezgebe Berhe, Hoa L Nguyen
Numerous risk factors have been linked to invasive candidiasis; however, they are nonspecific and often trigger empiric antifungal therapy in a large number of patients. Identification of more precise predictors could promote judicious use of empiric echinocandins. In this retrospective review, 127 patients with blood cultures positive for Candida spp. were compared to a randomly selected cohort of 134 patients on empiric micafungin for ≥3 days and with blood cultures negative for Candida spp. Factors associated with candidemia included total parenteral nutrition (TPN; 26...
January 2018: Proceedings of the Baylor University Medical Center
Jeffrey B Locke, Amanda L Almaguer, Joanna L Donatelli, Ken F Bartizal
Background: While echinocandins demonstrate excellent efficacy against Candida species in disseminated infections and demonstrate potent minimal inhibitory concentration (MIC) values under standard susceptibility testing conditions, investigation under conditions relevant to the vaginal environment was needed. We assessed the antifungal activity and time-kill kinetics of the novel echinocandin rezafungin (formerly CD101) under such conditions, against Candida species relevant to vulvovaginal candidiasis (VVC)...
2018: Infectious Diseases in Obstetrics and Gynecology
Cagla Bozkurt-Guzel, Mayram Hacioglu, Paul B Savage
Cationic steroid antimicrobials (CSA-ceragenin) are a new class of antimicrobial agent. In vitro activities of CSA-8, CSA-13, CSA-44, CSA-131, and CSA-138 and amphotericin B (AMP-B) were assessed against 50 nonrepeat Candida spp. isolates MICs, MFCs and combination studies were determined. Antibiofilm activities of CSAs, AMP-B, 2 azoles, and 2 echinocandins against Candida albicans were performed. Also, effects of coating the wells of plate with selected CSAs and antifungals were measured. The MIC50 (μg/mL) values of CSA-8, CSA-13, CSA-44, CSA-131, CSA-138, and AMP-B were 16, 1, 2, 1, 1, and 1, respectively...
March 28, 2018: Diagnostic Microbiology and Infectious Disease
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
Ashutosh Singh, Kelley R Healey, Priyanka Yadav, Gargi Upadhyaya, Neelam Sachdeva, Smita Sarma, Anil Kumar, Bansidhar Tarai, David S Perlin, Anuradha Chowdhary
Candida glabrata infections are increasing world-wide and exhibit greater rates of antifungal resistance than other species. DNA mismatch repair (MMR) gene deletions, such as msh2Δ , in C. glabrata resulting in a mutator phenotype has recently been reported to facilitate rapid acquisition of antifungal resistance. This study determined the antifungal susceptibility profile of 210 C. glabrata isolates, in 10 hospitals in India and investigated the impact of novel MSH 2 polymorphisms on mutation potential. No echinocandin or azole resistant strains were detected among C...
April 2, 2018: Antimicrobial Agents and Chemotherapy
Magdalini Tsekoura, Maria Ioannidou, Zoi-Dorothea Pana, Anna-Bettina Haidich, Charalampos Antachopoulos, Elias Iosifidis, George Kolios, Emmanuel Roilides
BACKGROUND: Echinocandins are recommended for the treatment of suspected or confirmed invasive candidiasis (IC) in adults. Less is known about the use of echinocandins for the management of IC in children. The aim of this study was to investigate the overall efficacy and safety of echinocandin class in neonatal and pediatric patients with IC. METHODS: PubMed, Cochrane Central, Scopus and Clinical trial registries were searched up to July 27, 2017. Eligible studies were randomized trials (RCTs) that evaluated the efficacy and safety of any echinocandin versus agents of other antifungal classes for the treatment of IC in pediatric patients...
March 24, 2018: Pediatric Infectious Disease Journal
Johanna Rhodes, Alireza Abdolrasouli, Rhys A Farrer, Christina A Cuomo, David M Aanensen, Darius Armstrong-James, Matthew C Fisher, Silke Schelenz
Candida auris was first described in 2009, and it has since caused nosocomial outbreaks, invasive infections, and fungaemia across at least 19 countries on five continents. An outbreak of C. auris occurred in a specialized cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak in the UK, involving a total of 72 patients. To understand the genetic epidemiology of C. auris infection both within this hospital and within a global context, we sequenced the outbreak isolate genomes using Oxford Nanopore Technologies and Illumina platforms to detect antifungal resistance alleles and reannotate the C...
March 29, 2018: Emerging Microbes & Infections
Tatsuro Hirayama, Taiga Miyazaki, Yuka Yamagishi, Hiroshige Mikamo, Takashi Ueda, Kazuhiko Nakajima, Yoshio Takesue, Yoshitsugu Higashi, Yoshihiro Yamamoto, Muneyoshi Kimura, Hideki Araoka, Shuichi Taniguchi, Yuichi Fukuda, Yumi Matsuo, Akiko Furutani, Kohei Yamashita, Takahiro Takazono, Tomomi Saijo, Shintaro Shimamura, Kazuko Yamamoto, Yoshifumi Imamura, Koichi Izumikawa, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae
The 46 clinical isolates of Candida guilliermondii and Candida famata were re-identified genetically, resulting in 27 C. guilliermondii and 12 Candida fermentati strains. The majority of C. guilliermondii , but no C. fermentati , were isolated from blood cultures. C. fermentati was more sensitive to antifungals, hydrogen peroxide and killing by murine macrophages than C. guilliermondii The C. guilliermondii isolates were echinocandin susceptible in vitro but resistant to micafungin in a murine model of invasive candidiasis...
March 26, 2018: Antimicrobial Agents and Chemotherapy
Xin Hou, Meng Xiao, He Wang, Shu-Ying Yu, Ge Zhang, Yanan Zhao, Ying-Chun Xu
Among 158 Candida glabrata bloodstream isolates collected from multicenter in China, resistance to fluconazole were seen in 8.9% of isolates. Three isolates (1.9%) were resistant to all echinocandins. MLST ST7 (65.8%) was the most common type and followed by ST3 (7.6%). PDR1 polymorphisms were associated with acquisition of fluconazole resistance in C. glabrata isolates, while MSH2 polymorphisms were associated with the STs and microsatellite genotypes, irrespective of fluconazole resistance.
March 26, 2018: Antimicrobial Agents and Chemotherapy
Ricardo Andreotti Siqueira, Andre Mario Doi, Paulo Petrus de Petrus Crossara, Paula Celia Mariko Koga, Alexandre Gimenes Marques, Fabiane Gomes Nunes, Jacyr Pasternak, Marines Dalla Valle Martino
BACKGROUND: An increased incidence of fungal infections caused by Candida species, especially Candida glabrata and Candida krusei, which are less susceptible to azoles, has been observed. Standardized susceptibility testing is essential for clinical management and for monitoring the epidemiology of resistance. AIMS: We evaluated the performance of two different susceptibility testing commercial methods, Vitek 2® and Sensititre YeastOne® , and compared them with the standard broth microdilution method (CLSI)...
March 23, 2018: Revista Iberoamericana de Micología
Greetje Vande Velde, Soňa Kucharíková, Patrick Van Dijck, Uwe Himmelreich
Fungal infections are a major problem for a growing number of mostly immune-compromised patients. Candida albicans is an important human fungal pathogen causing mucosal and deep tissue infections of which the majority is associated with biofilm formation on medical implants. The animal models that are currently in use to test antifungal drugs are limited to ex vivo analyses, requiring host sacrifice that excludes longitudinal monitoring of dynamic processes during biofilm formation in the live host. As a solution, we introduce non-invasive, dynamic imaging and quantification of C...
March 20, 2018: International Journal of Antimicrobial Agents
Eric H Jung, David J Meyers, Jürgen Bosch, Arturo Casadevall
Similarities in fungal and animal cells make antifungal discovery efforts more difficult than those for other classes of antimicrobial drugs. Currently, there are only three major classes of antifungal drugs used for the treatment of systemic fungal diseases: polyenes, azoles, and echinocandins. Even in situations where the offending fungal organism is susceptible to the available drugs, treatment courses can be lengthy and unsatisfactory, since eradication of infection is often very difficult, especially in individuals with impaired immunity...
March 2018: MSphere
J C Bader, E A Lakota, Shawn Flanagan, V Ong, Taylor Sandison, C M Rubino, S M Bhavnani, P G Ambrose
Rezafungin (CD101) is a novel echinocandin antifungal agent with activity against Aspergillus and Candida species, including azole- and echinocandin-resistant isolates. The objective of these analyses was to conduct pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses to evaluate single and once-weekly rezafungin dosing to provide dose selection support for future clinical studies. Using a previously developed rezafungin population PK model, Monte Carlo simulations were conducted utilizing the following three IV rezafungin dosing regimens: (i) single 400-mg dose, (ii) 400 mg for Week 1 followed by 200 mg weekly for 5 weeks, and (iii) 400 mg weekly for 6 weeks...
March 19, 2018: Antimicrobial Agents and Chemotherapy
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