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https://www.readbyqxmd.com/read/28634471/a-chitin-binding-protein-purified-from-moringa-oleifera-seeds-presents-anticandidal-activity-by-increasing-cell-membrane-permeability-and-reactive-oxygen-species-production
#1
João X S Neto, Mirella L Pereira, Jose T A Oliveira, Lady C B Rocha-Bezerra, Tiago D P Lopes, Helen P S Costa, Daniele O B Sousa, Bruno A M Rocha, Thalles B Grangeiro, José E C Freire, Ana Cristina O Monteiro-Moreira, Marina D P Lobo, Raimunda S N Brilhante, Ilka M Vasconcelos
Candida species are opportunistic pathogens that infect immunocompromised and/or immunosuppressed patients, particularly in hospital facilities, that besides representing a significant threat to health increase the risk of mortality. Apart from echinocandins and triazoles, which are well tolerated, most of the antifungal drugs used for candidiasis treatment can cause side effects and lead to the development of resistant strains. A promising alternative to the conventional treatments is the use of plant proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28630186/loss-of-c-5-sterol-desaturase-activity-results-in-increased-resistance-to-azole-and-echinocandin-antifungals-in-a-clinical-isolate-of-candida-parapsilosis
#2
Jeffrey M Rybak, C Michael Dickens, Josie E Parker, Kelly Caudle, Kayihura Manigaba, Sarah G Whaley, Andrew Nishimoto, Arturo Luna-Tapia, Sujoy Roy, Qing Zhang, Katherine S Barker, Glen E Palmer, Thomas R Sutter, Ramin Homayouni, Nathan P Wiederhold, Steven L Kelly, P David Rogers
Among emerging non-albicans Candida species, C. parapsilosis is of particular concern as a cause of nosocomial bloodstream infections in neonatal and intensive care unit patients. While fluconazole and echinocandins are considered effective treatment of such infections, recent reports of fluconazole and echinocandin resistance in C. parapsilosis indicate a growing problem. The present study describes a novel mechanism of antifungal resistance in this organism affecting the susceptibility of azole and echinocandin antifungals in a clinical isolate obtained from a patient with prosthetic valve endocarditis...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630180/de-novo-acquisition-of-resistance-to-scy-078-in-candida-glabrata-involves-fks-mutations-that-both-overlap-and-are-distinct-from-those-conferring-echinocandin-resistance
#3
Cristina Jiménez-Ortigosa, Winder B Perez, David Angulo, Katyna Borroto-Esoda, David S Perlin
SCY-078 is an orally active antifungal whose target is the β-(1,3)-D-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078 resistant Candida glabrata isolates following drug exposure in vitro Resistant isolates were analyzed using broth microdilution methodology and FKS sequencing. The kinetic inhibition parameter IC50 was also determined from GS complexes. The spectrum of resistance mutations found suggested a partially overlapping but independent binding site for SCY-078 relative to echinocandins on GS...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28625801/clinical-features-antifungal-susceptibility-and-outcome-of-candida-guilliermondii-fungemia-an-experience-in-a-tertiary-hospital-in-mid-taiwan
#4
Ting-Yu Tseng, Tsung-Chia Chen, Cheng-Mao Ho, Po-Chang Lin, Chia-Huei Chou, Chia-Ta Tsai, Jen-Hsien Wang, Chih-Yu Chi, Mao-Wang Ho
BACKGROUNDS: Candida guilliermondii is rarely isolated from clinical specimen. C. guilliermondii fungemia is seldom reported in the literature. The aims of this study were to report the clinical features, antifungal susceptibility, and outcomes of patients with C. guilliermondii fungemia. METHODS: From 2003 to 2015, we retrospectively analyzed the clinical and laboratory data of patients with C. guilliermondii fungemia in a tertiary hospital in mid-Taiwan. We performed a multivariable logistic regression analysis to identify the risk factors of mortality...
May 17, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28611248/the-aspergillus-fumigatus-crza-transcription-factor-activates-chitin-synthase-gene-expression-during-the-caspofungin-paradoxical-effect
#5
Laure Nicolas Annick Ries, Marina Campos Rocha, Patrícia Alves de Castro, Rafael Silva-Rocha, Roberto Nascimento Silva, Fernanda Zanolli Freitas, Leandro José de Assis, Maria Célia Bertolini, Iran Malavazi, Gustavo H Goldman
Aspergillus fumigatus is an opportunistic fungal pathogen that causes invasive aspergillosis (IA), a life-threatening disease in immunocompromised humans. The echinocandin caspofungin, adopted as a second-line therapy in combating IA, is a β-1,3-glucan synthase inhibitor, which, when used in high concentrations, reverts the anticipated A. fumigatus growth inhibition, a phenomenon called the "caspofungin paradoxical effect" (CPE). The CPE has been widely associated with increased chitin content in the cell wall due to a compensatory upregulation of chitin synthase-encoding genes...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28597967/anidulafungin-for-the-treatment-of-candidaemia-caused-by-candida-parapsilosis-analysis-of-pooled-data-from-six-prospective-clinical-studies
#6
Dimitrios P Kontoyiannis, Matteo Bassetti, Marcio Nucci, Maria Rita Capparella, Jean L Yan, Jalal Aram, Patricia A Hogan
Concerns with echinocandin use for infections caused by Candida parapsilosis complex species have driven the need for data to support echinocandin clinical efficacy in such patients. Data from six prospective studies were pooled to assess efficacy and safety of anidulafungin in patients with candidaemia caused by C. parapsilosis. Patient-level data were pooled from patients with microbiologically confirmed candidaemia due to C. parapsilosis treated with anidulafungin. Patients received a 200 mg intravenous (IV) loading dose of anidulafungin (day 1) and 100 mg daily thereafter...
June 9, 2017: Mycoses
https://www.readbyqxmd.com/read/28597394/invasive-candidiasis-in-brescia-italy-analysis-of-species-distribution-and-antifungal-susceptibilities-during-seven-years
#7
M A De Francesco, G Piccinelli, M Gelmi, F Gargiulo, G Ravizzola, G Pinsi, L Peroni, C Bonfanti, A Caruso
The aims of this study were to evaluate the epidemiology of nosocomial candidemia in a large teaching hospital in Brescia, Italy, and the in vitro antifungal susceptibility of isolates. We analyzed 196 isolates causing fungemia in patients admitted in our hospital, between January 2009 and December 2015. Strains were identified by VITEK 2 and MALDI-TOF MS. MICs were determined by Sensititre Yeast OneTM. The resistance was defined by using the revised CLSI breakpoints/epidemiological cutoff values to assign susceptibility or wild type to systemic antifungal agents...
June 8, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28588560/molecular-epidemiology-and-antifungal-susceptibility-of-candida-glabrata-in-china-august-2009-to-july-2014-a-multi-center-study
#8
Xin Hou, Meng Xiao, Sharon C-A Chen, Fanrong Kong, He Wang, Yun-Zhuo Chu, Mei Kang, Zi-Yong Sun, Zhi-Dong Hu, Ruo-Yu Li, Juan Lu, Kang Liao, Tie-Shi Hu, Yu-Xing Ni, Gui-Ling Zou, Ge Zhang, Xin Fan, Yu-Pei Zhao, Ying-Chun Xu
Candida glabrata is an increasingly important cause of invasive candidiasis. In China, relatively little is known of the molecular epidemiology of C. glabrata and of its antifungal susceptibility patterns. Here we studied 411 non-duplicate C. glabrata isolates from 411 patients at 11 hospitals participating in the National China Hospital Invasive Fungal Surveillance Net program (CHIF-NET; 2010-2014). Genotyping was performed using multilocus sequence typing (MLST) employing six genetic loci and by microsatellite analysis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28584138/initial-treatment-of-cancer-patients-with-fluconazole-susceptible-dose-dependent-candida-glabrata-fungemia-better-outcome-with-an-echinocandin-or-polyene-compared-to-an-azole
#9
Audrey Le, Dimitrios Farmakiotis, Jeffrey J Tarrand, Dimitrios P Kontoyiannis
28-day crude mortality in 68 cancer patients with fluconazole susceptible dose-dependent Candida glabrata fungemia started on treatment (within 48 hours after blood culture collection) with an echinocandin or liposomal amphotericin-B was better (30%), compared to those treated with azole monotherapy (52%, p=0.07). After adjusting for confounders, azole monotherapy was associated with worse 28-day survival (hazard ratio 3.8, p=0.003).
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28574735/fatal-course-of-saprochaete-capitata-fungemia-in-children-with-acute-lymphoblastic-leukemia
#10
Zeynep Canan Özdemir, Ayşe Bozkurt Turhan, Yeter Düzenli Kar, Çağrı Ener Dinleyici, Özcan Bör
Saprochaete capitata (S. capitata) is a very rare fungal pathogen that causes disseminated opportunistic infections in patients with hematologic malignancies. Fever resistant to broad-spectrum antibiotic and antifungal treatment is common in the presence of fungemia during the period of profound neutropenia. We describe three cases of leukemic children who died from S. capitata fungemia following a first febrile neutropenic episode after the induction of chemotherapy. S. capitata fungemia is an emergent infection associated with high mortality and low susceptibility to fluconazole and echinocandins...
June 2, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/28566368/caspofungin-increases-fungal-chitin-and-eosinophil-and-%C3%AE-%C3%AE-t-cell-dependent-pathology-in-invasive-aspergillosis
#11
Nansalmaa Amarsaikhan, Ethan M Sands, Anand Shah, Ali Abdolrasouli, Anna Reed, James E Slaven, Darius Armstrong-James, Steven P Templeton
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A...
May 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28560585/creation-characterization-and-utilization-of-cryptococcus-neoformans-mutants-sensitive-to-micafungin
#12
Akio Toh-E, Misako Ohkusu, Kiminori Shimizu, Masashi Yamaguchi, Naruhiko Ishiwada, Akira Watanabe, Katsuhiko Kamei
We constructed deletion mutants of Cryptococcus neoformans var neoformans (serotype D) genes encoding late ergosterol biosynthetic pathway enzymes and found that the mutations enhanced susceptibility to various drugs including micafungin, one of the echinocandins, to which wild-type Cryptococcus strains show no susceptibility. Furthermore, through isolation of a mutant resistant to micafungin from a micafungin-sensitive erg mutant and genetic analysis of it, we found that the responsible mutation occurred in the hotspot 2 of FKS1 encoding β-1, 3-glucan synthase, indicating that micafungin inhibited the growth of the erg mutant via inhibiting Fks1 activity...
May 30, 2017: Current Genetics
https://www.readbyqxmd.com/read/28559257/susceptibility-testing-of-the-echinocandins-against-candida-species-in-the-daily-routine-etest%C3%A2-versus-sensititre-yeastone%C3%A2-data-from-a-single-center-in-austria
#13
Maria Aigner, Thomas Erbeznik, Martin Gschwentner, Cornelia Lass-Flörl
Antifungal susceptibility testing of caspofungin, anidulafungin and micafungin against Candida species was performed to evaluate the role of ETest® and Sensititre YeastOne® for antifungal susceptibility testing for daily routine and to survey resistance. 104 Candida species isolates detected from blood cultures were investigated. Determining EUCAST broth microdilution as reference method essential agreement (EA), categorical agreement (CA), very major errors (VME), major (ME) and minor errors (MIN) were assessed reading MICs at 18, 24 and 48 hours...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28548995/invasive-fungal-infections-following-liver-transplantation
#14
Rachel Hogen, Kiran Dhanireddy
PURPOSE OF REVIEW: The review outlines the microbiology, presentation, prophylactic strategies, resistance patterns, and consequences of invasive fungal infections (IFIs) in orthotopic liver transplantation (OLT) recipients. RECENT FINDINGS: There has been an increase in the proportion of non-albicans Candida causing IFIs. The biomarkers galactomannan and β-D-glucan should not be routinely used in the diagnosis of IFIs in OLT recipients due to their limited accuracy...
May 25, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28533234/differential-activity-of-the-oral-glucan-synthase-inhibitor-scy-078-against-wild-type-and-echinocandin-resistant-strains-of-candida-spp
#15
Michael A Pfaller, Shawn A Messer, Paul R Rhomberg, Mariana Castanheira
SCY-078 (formerly MK-3118) is a novel orally active inhibitor of fungal β- (1, 3)-glucan synthase (GS). SCY-078 is a derivative of enfumafungin and is structurally distinct from the echinocandin class of antifungal agents. We evaluated the in vitro activity of this compound against wild-type (WT) and echinocandin-resistant isolates containing mutations in the FKS genes of Candida spp. Against 36 Candida spp. FKS mutants tested, 30 (83.3%) were non-WT to 1 or more echinocandins and only 9 (25.0%) were non-WT (MIC, >WT-upper limit) to SCY-078...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28513771/species-distribution-and-antifungal-susceptibility-patterns-of-candida-isolates-from-a-public-tertiary-teaching-hospital-in-the-eastern-cape-province-south-africa
#16
P Mnge, B I Okeleye, S D Vasaikar, T Apalata
Candida species are the leading cause of invasive fungal infections, and over the past decade there has been an increased isolation of drug resistant Candida species. This study aimed to identify the species distribution of Candida isolates and to determine their unique antifungal susceptibility and resistance patterns. During a cross-sectional study, 209 Candida isolates (recovered from 206 clinical samples) were collected and their species distribution was determined using ChromAgar Candida. The Vitek-2 system (Biomerieux, South Africa) was used to determine minimum inhibitory concentrations (MICs) to azoles (fluconazole, voriconazole), echinocandins (caspofungin, micafungin), polyenes (amphotericin B) and flucytosine...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28510690/trichosporonosis-in-pediatric-patients-with-a-hematologic-disorder
#17
Catherine E Foster, Morven S Edwards, Julienne Brackett, Deborah A Schady, C Mary Healy, Carol J Baker
Background.: Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking. Methods.: We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder...
May 16, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28501465/candiduria-evidence-based-approach-to-management-are-we-there-yet
#18
REVIEW
W A Alfouzan, R Dhar
Candiduria is considered one of the most controversial issues in patient management. Neither the diagnosis nor the optimal treatment options are standardized. This is further complicated by lack of defined laboratory criteria for diagnosis as most of the studies were set for bacterial rather than fungal urinary tract infection (UTI). Furthermore, since Candida species is a known commensal of the genitourinary tract its presence in the urine sample adds ambiguity to making a definitive diagnosis of candidal UTI...
May 10, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28499959/impact-of-initial-empirical-antifungal-agents-on-the-outcome-of-critically-ill-patients-with-invasive-candidiasis-analysis-of-the-china-scan-study
#19
Na Cui, Hao Wang, Haibo Qiu, Ruoyu Li, Dawei Liu
The effect of different empirical antifungal agents on the clinical outcome of critically ill patients with invasive candidiasis (IC) has not been fully elucidated. In this study, 136 patients with proven IC who received empirical therapy in the China-SCAN multicentre study were retrospectively analysed. Initial empirical antifungal monotherapy consisted of a triazole [fluconazole (n = 61), voriconazole (n = 20) or itraconazole (n = 12)] or an echinocandin (n = 43). Hospital mortality as the primary outcome and global responses (clinical and microbiological) were assessed...
May 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28496146/the-antifungal-pipeline-a-reality-check
#20
REVIEW
John R Perfect
Invasive fungal infections continue to appear in record numbers as the immunocompromised population of the world increases, owing partially to the increased number of individuals who are infected with HIV and partially to the successful treatment of serious underlying diseases. The effectiveness of current antifungal therapies - polyenes, flucytosine, azoles and echinocandins (as monotherapies or in combinations for prophylaxis, or as empiric, pre-emptive or specific therapies) - in the management of these infections has plateaued...
May 12, 2017: Nature Reviews. Drug Discovery
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