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https://www.readbyqxmd.com/read/28705674/molecular-bases-of-antifungal-resistance-in-filamentous-fungi
#1
Cheshta Sharma, Anuradha Chowdhary
Invasive mould infections due to Aspergillus species, Fusarium spp., Scedosporium spp. and other filamentous fungi remain a significant cause of morbidity and mortality in immunocompromised patients. Antifungal therapy is required for successful patient management; however, limited antifungal drugs and emergence of drug resistance pose a challenge to the clinicians for the effective management of the disease. The evolution of multidrug resistant strains due to selective pressure and the intrinsically resistant pathogenic species are a major concern...
July 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28702763/pharmacokinetics-of-antifungal-drugs-practical-implications-for-optimized-treatment-of-patients
#2
REVIEW
Romuald Bellmann, Piotr Smuszkiewicz
INTRODUCTION: Because of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety. MATERIALS AND METHODS: This review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy. CONCLUSIONS AND DISCUSSION: Amphotericin B is eliminated unchanged via urine and faeces...
July 12, 2017: Infection
https://www.readbyqxmd.com/read/28699797/candidemia-and-invasive-candidiasis-among-hospitalized-neonates-and-pediatric-patients
#3
Rachel Harrington, Sylvia L Kindermann, Qingjiang Hou, Robert J Taylor, Nkechi Azie, David L Horn
OBJECTIVE: To investigate the epidemiology, treatment, length of stay (LOS) and costs for neonatal and pediatric inpatients with invasive candidiasis (IC). METHODS: The Cerner Health Facts Database was used to assess inpatients (2005-2014) identified by positive blood or cerebrospinal fluid (CSF) Candida cultures. Log-transformed LOS and cost were examined in candidemia-only patients (n= 191) using multivariable linear regression. RESULTS: 202 patients had a positive culture (blood: n = 192; CSF: n = 10; both: n = 2)...
July 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28696236/combination-therapy-with-isavuconazole-and-micafungin-for-treatment-of-experimental-invasive-pulmonary-aspergillosis
#4
Vidmantas Petraitis, Ruta Petraitiene, Matthew W McCarthy, Laura L Kovanda, Myo H Zaw, Kaiser Hussain, Naima Shaikh, Bo Bo W Maung, Navjot K Sekhon, William W Hope, Thomas J Walsh
Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in immunocompromised patients. We hypothesized that simultaneous inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1→3)-β-D-glucan in the cell wall, respectively, by the antifungal triazole isavuconazole and the echinocandin micafungin, may result in improved outcome in experimental IPA in persistently neutropenic rabbits. Treatment groups included isavuconazole (ISA) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg/kg/day, micafungin at 2 mg/kg/day (MFG2), or combinations of (ISA20+MFG2), (ISA40+MFG2), (ISA60+MFG2), and untreated rabbits (UC)...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28693479/pharmacoeconomic-analysis-of-antifungal-therapy-for-primary-treatment-of-invasive-candidiasis-caused-by-candida-albicans-and-non-albicans-candida-species
#5
Huang-Tz Ou, Tsung-Ying Lee, Yee-Chun Chen, Claudie Charbonneau
BACKGROUND: Cost-effectiveness studies of echinocandins for the treatment of invasive candidiasis, including candidemia, are rare in Asia. No study has determined whether echinocandins are cost-effective for both Candida albicans and non-albicans Candida species. There have been no economic evaluations that compare non-echinocandins with the three available echinocandins. This study was aimed to assess the cost-effectiveness of individual echinocandins, namely caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C...
July 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28689871/cd101-a-long-acting-echinocandin-and-comparator-antifungal-agents-tested-against-a-global-collection-of-invasive-fungal-isolates-in-the-sentry-2015-antifungal-surveillance-program
#6
Michael A Pfaller, Shawn A Messer, Paul R Rhomberg, Mariana Castanheira
CD101 is a novel echinocandin with exceptional chemical stability and long-acting pharmacokinetics. The activity of CD101 and comparators was evaluated using CLSI broth microdilution methods against 713 invasive fungal isolates, including 589 Candida spp. (6 species), 14 C. neoformans, 97 A. fumigatus and 13 A. flavus species complex collected worldwide during 2015. All C. tropicalis, C. krusei and C. dubliniensis, 99.7% of C. albicans and 98.3% of C. glabrata were inhibited by ≤0.12 µg/mL of CD101, and these isolates were susceptible/wild type to other echinocandins using CLSI clinical breakpoint and epidemiological cutoff value (ECV) interpretive criteria...
July 6, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28686553/candidaemia-in-a-tertiary-care-academic-hospital-in-italy-the-impact-of-c-parapsilosis-complex-on-the-species-distribution-and-antifungal-susceptibility
#7
Maria Cristina Ghezzi, Grazia Brunetti, Valeria Visconti, Alessandra Giordano, Giammarco Raponi
PURPOSE: To analyse the species distribution and the susceptibility profiles to the major antifungal agents of Candida isolated from bloodstream infections (BSIs) in both intensive care units (ICUs) and non-ICU wards in a tertiary care hospital in Italy from 2010 until 2015. METHODOLOGY: Episodes of Candida BSI were recorded in a retrospective observational cohort study. Yeasts were isolated from both blood and intravascuIar devices (IVDs) and their susceptibility to antifungal drugs was tested using the microdilution method...
July 8, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28681815/identification-of-the-paradoxical-effect-of-caspofungin-and-micafungin-on-candida-albicans-growth-in-vitro-using-a-growth-curve-methodology
#8
Huang Zhouying, Li Chen, Wang Ruiqi, Liao Kang, Zeng Ji
BACKGROUND: The paradoxical effect of fungi, (which is a special phenomenon that certain Candida spp. might exhibit augmented growth in the presence of echinocandin at some concentration higher than the minimum inhibitory concentration) would be better illustrated through growth curves. MATERIALS AND METHODS: We investigated the paradoxical effect of caspofungin and micafungin on the growth and cell viability of 38 clinical isolates of Candida albicans using a microbial sensitivity test and growth curve methodology...
April 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28681316/donor-derived-candida-stellimalicola-in-a-clinical-specimen-preservation-fluid-contamination-during-pancreas-procurement
#9
Damien Dupont, Antoine Huguenin, Elodie Tisserand, Véronique Reiter, Emmanuel Morelon, Lionel Badet, Isabelle Villena, Martine Wallon, Dominique Toubas
We report here a case of possible donor-derived Candida stellimalicola infection after pancreas transplantation. Candida stellimalicola, an environmental non-filamentous yeast, was isolated from both the peritoneal fluid of the graft donor and the preservation fluid of the transplanted pancreas. Interestingly, this strain exhibited high minimum inhibitory concentrations to azoles. These results justified the use of echinocandins as therapy instead of fluconazole. This switch permitted a favorable outcome. To our knowledge, this is the first report of C...
July 5, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28669831/epidemiology-of-antifungal-resistance-in-human-pathogenic-yeasts-current-viewpoint-and-practical-recommendations-for-management
#10
Dimitrios Farmakiotis, Dimitrios P Kontoyiannis
In this review, we describe the epidemiology and clinical significance of resistance in Candida spp. and other non-Cryptococcus yeasts. The rise in echinocandin resistance, azole resistance and cross-resistance to ≥2 antifungal classes (multi-drug resistance: MDR) has been a worrisome trend, mainly in US large tertiary and oncology centers, particularly as it relates to C. glabrata. C. kefyr is also a concern, as it can be resistant to echinocandins and polyenes, especially in patients with hematologic malignancies...
June 29, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28653258/azole-resistance-in-aspergillus-fumigatus-in-patients-with-cystic-fibrosis-a-matter-of-concern
#11
A Hamprecht, F Morio, O Bader, P Le Pape, J Steinmann, E Dannaoui
Aspergillus fumigatus is the most frequent filamentous fungus isolated from respiratory specimens from patients with cystic fibrosis (CF). Triazoles are the most widely used antifungals in the treatment of allergic bronchopulmonary aspergillosis (ABPA) and invasive aspergillosis (IA) in CF patients. Treatment success could be severely compromised by the occurrence of azole-resistant A. fumigatus (ARAf), which is increasingly reported worldwide from both clinical samples and the environment. In previous studies, ARAf has been detected in up to 8% of CF patients...
June 26, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28652784/current-perspective-on-emergence-diagnosis-and-drug-resistance-in-candida-auris
#12
REVIEW
Smita Sarma, Shalini Upadhyay
Candida auris is an emerging fungus that presents a serious threat to global health. The organism is difficult to identify using conventional biochemical methods. C. auris has also attracted attention because of its reduced susceptibility to azoles, polyenes, and echinocandins, with a few strains even resistant to all three classes of antifungals. In this review paper we discuss the trends in emergence of C. auris in different parts of the world, associated risk factors, drug resistance, and diagnostic challenges...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28652216/fungemia-and-necrotic-lymph-node-infection-with-sporopachydermia-cereana-in-a-patient-with-acute-myeloid-leukemia
#13
Craig Kingston, Michael Medinger, Florian Banderet-Uglioni, Stefano Bassetti, Mario Bargetzi, Sebastian Haubitz, Christoph A Fux, Veronika Bättig, Daniel Goldenberger, Jakob Passweg, Marc Heizmann
Sporopachydermia cereana is a rare yeast found in necrotic cactus tissue, predominantly in the Americas. Infection in humans with clinical data has only been reported in four patients so far, all of whom died, either directly from the pathogen or from other complications of immunosuppression. Treatment of the yeast is complicated by difficulties in identification of the pathogen with conventional diagnostic techniques and by intrinsic resistance to echinocandins. The first patient to survive a disseminated infection with S...
June 23, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#14
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/28634471/a-chitin-binding-protein-purified-from-moringa-oleifera-seeds-presents-anticandidal-activity-by-increasing-cell-membrane-permeability-and-reactive-oxygen-species-production
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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