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H-L Lei, L-H Li, W-S Chen, W-N Song, Y He, F-Y Hu, X-J Chen, W-P Cai, X-P Tang
Talaromyces marneffei (T. marneffei) can cause talaromycosis, a fatal systemic mycosis, in patients with AIDS. With the increasing number of talaromycosis cases in Guangdong, China, we aimed to investigate the susceptibility of 189 T. marneffei clinical strains to eight antifungal agents, including three echinocandins (anidulafungin, micafungin, and caspofungin), four azoles (posaconazole, itraconazole, voriconazole, and fluconazole), and amphotericin B, with determining minimal inhibition concentrations (MIC) by Sensititre YeastOne™ YO10 assay in the yeast phase...
March 13, 2018: European Journal of Clinical Microbiology & Infectious Diseases
Qun Yue, Yan Li, Li Chen, Xiaoling Zhang, Xingzhong Liu, Zhiqiang An, Gerald F Bills
The echinocandins are antifungal lipopeptides targeting fungi via noncompetitive inhibition of the β-1,3-D-glucan synthase FKS1 subunit. A novel echinocandin resistance mechanism involving an auxiliary copy of FKS1 in echinocandin-producing fungus Pezicula radicicola NRRL 12192 was discovered. We sequenced the genome of NRRL 12192 and predicted two FKS1-encoding genes (prfks1n and prfks1a), rather than a single FKS1 gene typical of filamentous ascomycetes. The prfks1a gene sits immediately adjacent to an echinocandin (sporiofungin) gene cluster which was confirmed by disruption of prnrps4 and abolishment of sporiofungin production...
March 12, 2018: Environmental Microbiology
Kaitlin Benedict, Monika Roy, Sarah Kabbani, Evan J Anderson, Monica M Farley, Sasha Harb, Lee H Harrison, Lindsay Bonner, Vijitha Lahanda Wadu, Kaytlyn Marceaux, Rosemary Hollick, Zintar G Beldavs, Alexia Y Zhang, William Schaffner, Caroline R Graber, Gordana Derado, Tom M Chiller, Shawn R Lockhart, Snigdha Vallabhaneni
Introduction: Candida is a leading cause of healthcare-associated bloodstream infections in the United States. Infants and children have unique risk factors for candidemia, and the Candida species distribution in this group is different that among adults; however, candidemia epidemiology in this population has not been described recently. Methods: We conducted active population-based candidemia surveillance in 4 US metropolitan areas between 2009 and 2015. We calculated incidences among neonates (0-30 days old), infants (0-364 days old), and noninfant children (1-19 years old), documented their clinical features and antifungal drug resistance...
March 7, 2018: Journal of the Pediatric Infectious Diseases Society
Sarah G Whaley, Kelly E Caudle, Lucia Simonicova, Qing Zhang, W Scott Moye-Rowley, P David Rogers
The high prevalence of fluconazole resistance among clinical isolates of Candida glabrata has greatly hampered the utility of fluconazole for the treatment of invasive candidiasis. Fluconazole resistance in this yeast is almost exclusively due to activating mutations in the transcription factor Pdr1, which result in upregulation of the ABC transporter genes CDR1 , PDH1 , and SNQ2 and therefore increased fluconazole efflux. However, the regulation of Pdr1 is poorly understood. In order to identify genes that interact with the Pdr1 transcriptional pathway and influence the susceptibility of C...
January 2018: MSphere
Todd P McCarty, Shawn R Lockhart, Stephen A Moser, Jennifer Whiddon, Joanna Zurko, Cau D Pham, Peter G Pappas
Objectives: To identify the frequency of micafungin resistance among clinically significant isolates of Candida stored at our institution from 2005 to 2015. Chart review of patients with resistant isolates then informed the clinical setting and outcomes associated with these infections. Methods: Clinical Candida isolates had been stored at -80°C in Brucella broth with 20% glycerol from 2005. Isolates were tested using broth microdilution to determine micafungin MICs...
February 28, 2018: Journal of Antimicrobial Chemotherapy
Maiken Cavling Arendrup, Joseph Meletiadis, Oscar Zaragoza, Karin Meinike Jørgensen, Laura Judith Marcos-Zambrano, Lamprini Kanioura, Manuel Cuenca-Estrella, Johan W Mouton, Jesus Guinea
OBJECTIVES: Rezafungin (CD101) is a new long-acting echinocandin allowing weekly dosing, currently undergoing phase-II clinical trials for invasive candidiasis. The aim of this study was to assess rezafungin's in vitro activity against the most frequent Candida species following the EUCAST methodology. METHODS: The susceptibility of 2,018 clinical Candida isolates was determined at four European laboratories. In parallel, six control strains were repeatedly tested...
March 2, 2018: Clinical Microbiology and Infection
Mobaswar Hossain Chowdhury, Lisa Kathleen Ryan, Kartikeya Cherabuddi, Katie B Freeman, Damian G Weaver, Jeffry C Pelletier, Richard W Scott, Gill Diamond
Invasive candidiasis caused by Candida albicans and non- albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C...
February 27, 2018: Journal of Fungi (Basel, Switzerland)
Mariana Elizondo-Zertuche, Rogelio de J Treviño-Rangel, Efrén Robledo-Leal, Carolina E Luna-Rodríguez, Margarita L Martínez-Fierro, Iram P Rodríguez-Sánchez, Gloria M González
The genus Scedosporium is a complex of ubiquitous moulds associated with a wide spectrum of clinical entities, with high mortality principally in immunocompromised hosts. Ecology of these microorganisms has been studied performing isolations from environmental sources, showing a preference for human-impacted environments. This study aimed to evaluate the presence and antifungal susceptibility of Scedosporium complex species in soil samples collected in high-human-activity sites of Mexico. A total of 97 soil samples from 25 Mexican states were collected...
December 13, 2017: Mycologia
Iris Nora Tiraboschi, Natalia Cintia Pozzi, Luciana Farías, Susana García, Norma Beatriz Fernández
BACKGROUND: The epidemiology of candidemia vary by region. AIM: To determine the epidemiology of candidemia in a hospital for 16 years. MATERIAL AND METHODS: Episodes of candidemia occurred in the Hospital de Clinicas of Buenos Aires were reviewed, from 01/01/98 to 31/12/13. RESULTS: 374 episodes of candidemia were identified. The incidence was 2.21/1,000 discharges and increased from 1.96 (1998-2005) to 2.25 (2006-2013) (p = 0...
October 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Rogelio de J Treviño-Rangel, José F Espinosa-Pérez, Hiram Villanueva-Lozano, Alexandra M Montoya, Angel Andrade, Alexandro Bonifaz, Gloria M González
Candida bracarensis is an emerging cryptic species within the Candida glabrata clade. To date, little is known about its epidemiology, virulence, and antifungal susceptibility. This study documents the occurrence of C. bracarensis for the first time in Mexico and focuses on its in vitro production of hydrolytic enzymes, as well as antifungal susceptibility to echinocandins. This strain was isolated from a vaginal swab of a female with vulvovaginal candidosis; exhibited a very strong activity of aspartyl proteinase, phospholipase, and hemolysin; and was susceptible to caspofungin, anidulafungin, and micafungin (MIC = 0...
February 27, 2018: Folia Microbiologica
Amelia K Sofjan, Ardath Mitchell, Dhara N Shah, Tam Nguyen, Mui Sim, Ashley Trojcak, Nicholas D Beyda, Kevin W Garey
BACKGROUND: Rezafungin (CD101) is a novel echinocandin currently under development. The purpose of this study was to perform a systematic literature review of published evidence on CD101 and an antimicrobial stewardship audit of real-world use of echinocandins to determine areas of unmet medical need and potential places in therapy for rezafungin. METHODS: A systematic literature review on rezafungin identified eight peer-reviewed manuscripts and 19 separate abstracts...
February 24, 2018: Journal of Global Antimicrobial Resistance
José Pedro Guirao-Abad, Ruth Sánchez-Fresneda, Francisco Machado, Juan Carlos Argüelles, María Martínez-Esparza
Micafungin belongs to the antifungal family of echinocandins, which act as non-competitive inhibitors of the fungal cell-wall β-1,3-D-glucan synthase. Since C. albicans is the most prevalent pathogenic fungus in humans, we study the involvement of Micafungin in the modulation of the inflammatory response developed by human tissue macrophages against C. albicans The MIC for Micafungin was 0.016 μg/ml on the C. albicans SC5314 standard strain. Micafungin induced a drastic reduction in the number of exponential SC5314 viable cells, the fungicidal effect being dependent on the cellular metabolic activity...
February 26, 2018: Antimicrobial Agents and Chemotherapy
Melanie T Cushion, Alan Ashbaugh, Keeley Hendrix, Michael J Linke, Nikeya Tisdale, Steven G Sayson, Aleksey Porollo
The echinocandins are a class of anti-fungal agents that target β-1,3-D-glucan (BG) biosynthesis. In the ascigerous Pneumocystis species, treatment with these drugs deplete the asci life cycle stage which contain BG, but large numbers of forms which do not express BG remain in the infected lungs. In the present study, the gene expression profiles of Pneumocystis murina were compared between infected untreated mice and those treated with anidulafungin for 2 weeks to understand the metabolism of the persisting forms...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Joseph Meletiadis, Maria Siopi, Athanassios Tsakris, Johan W Mouton, Spyros Pournaras
The lack of a quantifiable marker for echinocandins activity hinders in vitro PK/PD studies for Aspergillus spp. We developed an in vitro PK/PD model simulating anidulafungin pharmacokinetics and assessing its pharmacodynamics against A. fumigatus with a new easily quantifiable, sensitive and reproducible marker. Two clinical A. fumigatus isolates previously used in animals (AZN8196,V52-35) with identical anidulafungin EUCAST (0.03 μg/ml) and CLSI (0.015 μg/ml) MEC and one (AFU79728) with MEC>16 μg/ml were tested in a two-compartment PK/PD dialysis/diffusion closed model containing a dialysis membrane tube (DM) inoculated with 103 cfu/mL...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Giovanni L Breda, Felipe F Tuon, Jacques F Meis, Patricia F Herkert, Ferry Hagen, Letícia Z de Oliveira, Viviane de Carvalho Dias, Clóvis Arns da Cunha, Flávio Queiroz-Telles
Candidemia is the main invasive fungal disease among hospitalized patients. Several breakthrough candidemia (BrC) cases have been reported, but few studies evaluate the epidemiology, risk factors, molecular characterization, antifungal susceptibility profile and outcome of those patients, especially in developing countries and including patients using broad spectrum antifungals. We conducted a retrospective study from 2011 to 2016, including patients aged 12 years or older with candidemia. Epidemiological characteristics and risk factors for candidemia were evaluated and compared with patients with BrC using univariate and multivariate analysis...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
João P Z Siqueira, Deanna A Sutton, Josepa Gené, Dania García, Nathan Wiederhold, Josep Guarro
The diversity of Aspergillus species in clinical samples is continuously increasing. Species under the former name Eurotium, currently accommodated in section Aspergillus of the genus Aspergillus, are xerophilic fungi widely found in the human environment and able to grow on substrates with low water activity. However, their prevalence in the clinical setting is poorly known. We have studied the presence of these species in a set of clinical samples from the United States using a multilocus sequence analysis based on the internal transcribed spacer (ITS) region of the rRNA, and fragments of the genes β-tubulin (BenA), calmodulin (CaM), and polymerase II second largest subunit (RPB2)...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Ashraf A Kadry, Amira M El-Ganiny, Rasha A Mosbah, Susan G W Kaminskyj
Systemic human fungal infections are increasingly common. Aspergillus species cause most of the airborne fungal infections. Life-threatening invasive aspergillosis was formerly found only in immune-suppressed patients, but recently some strains of A. fumigatus have become primary pathogens. Many fungal cell wall components are absent from mammalian systems, so they are potential drug targets. Cell-wall-targeting drugs such as echinocandins are used clinically, although echinocandin-resistant strains were discovered shortly after their introduction...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Meng Xiao, Xin Fan, Xin Hou, Sharon Ca Chen, He Wang, Fanrong Kong, Zi-Yong Sun, Yun-Zhuo Chu, Ying-Chun Xu
Echinocandin antifungal agents have become the first-line therapy for invasive candidiasis (IC) in many countries. Despite their increasing use, resistance to this class of drug is, overall, still uncommon. Here, we report two patients from the People's Republic of China with IC, one with infection caused by pan-echinocandin-resistant Candida tropicalis and the other by pan-echinocandin-resistant Candida glabrata. We also describe the mechanisms of drug resistance of these isolates. The echinocandin-resistant C...
2018: Infection and Drug Resistance
Ilan S Schwartz, Thomas F Patterson
PURPOSE OF REVIEW: The global emergence of antifungal resistance among Candida spp. and Aspergillus spp. will disproportionately affect transplantation recipients, who are prone to invasive fungal disease. RECENT FINDINGS: Invasive candidiasis is increasingly caused by non-albicans Candida species with reduced susceptibility to first-line antifungals. Echinocandin resistance in Candida glabrata is increasing in some settings. Candida auris has rapidly emerged as a global concern due to multidrug resistance and efficient nosocomial spread in healthcare settings...
February 5, 2018: Current Infectious Disease Reports
Maria N Gamaletsou, Thomas J Walsh, Nikolaos V Sipsas
Invasive fungal infections caused by drug-resistant organisms, are an emerging threat to heavily immunosuppressed patients with haematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis, empirical and pre-emptive therapy result in long term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the non-linear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors...
February 2, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
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