scholarly journals The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

2020 ◽  
Vol 6 (3) ◽  
pp. 138 ◽  
Author(s):  
Amir Arastehfar ◽  
Cornelia Lass-Flörl ◽  
Rocio Garcia-Rubio ◽  
Farnaz Daneshnia ◽  
Macit Ilkit ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Fungal Species ◽  
Antifungal Resistance ◽  
Candida Auris ◽  
Recent Emergence ◽  
Invasive Infections

Human fungal pathogens are attributable to a significant economic burden and mortality worldwide. Antifungal treatments, although limited in number, play a pivotal role in decreasing mortality and morbidities posed by invasive fungal infections (IFIs). However, the recent emergence of multidrug-resistant Candida auris and Candida glabrata and acquiring invasive infections due to azole-resistant C. parapsilosis, C. tropicalis, and Aspergillus spp. in azole-naïve patients pose a serious health threat considering the limited number of systemic antifungals available to treat IFIs. Although advancing for major fungal pathogens, the understanding of fungal attributes contributing to antifungal resistance is just emerging for several clinically important MDR fungal pathogens. Further complicating the matter are the distinct differences in antifungal resistance mechanisms among various fungal species in which one or more mechanisms may contribute to the resistance phenotype. In this review, we attempt to summarize the burden of antifungal resistance for selected non-albicansCandida and clinically important Aspergillus species together with their phylogenetic placement on the tree of life. Moreover, we highlight the different molecular mechanisms between antifungal tolerance and resistance, and comprehensively discuss the molecular mechanisms of antifungal resistance in a species level.

scholarly journals Antifungal Resistance: Specific Focus on Multidrug Resistance in Candida auris and Secondary Azole Resistance in Aspergillus fumigatus

2018 ◽  
Vol 4 (4) ◽  
pp. 129 ◽  
Author(s):  
Sevtap Arikan-Akdagli ◽  
Mahmoud Ghannoum ◽  
Jacques Meis
Keyword(s):  
Aspergillus Fumigatus ◽  
Molecular Mechanisms ◽  
Multidrug Resistant ◽  
Fungal Species ◽  
Antifungal Resistance ◽  
Current Status ◽  
Clinical Implications ◽  
Azole Resistance ◽  
Candida Auris

Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for the clinical implications and the extent of correlation of in vitro resistance to clinical outcomes. This review article summarizes the epidemiology of C. auris infections, animal models focusing on the activity of novel antifungal compounds in C. auris infections, virulence factors, and the mechanisms of antifungal resistance for this multi-resistant Candida species. Regarding A. fumigatus, the significance of azoles in the treatment of A. fumigatus infections, reference methods available for the detection of resistance in vitro, molecular mechanisms of secondary azole resistance, routes of acquisition, and clinical implications of in vitro resistance are covered to provide guidance for the current status of azole resistance in A. fumigatus.

Resistance to antifungal therapies

2017 ◽  
Vol 61 (1) ◽  
pp. 157-166 ◽  
Author(s):  
Rajendra Prasad ◽  
Atanu Banerjee ◽  
Abdul Haseeb Shah
Keyword(s):  
Fungal Pathogens ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Therapeutic Strategies ◽  
Antifungal Resistance ◽  
Antifungal Drugs ◽  
Therapeutic Interventions ◽  
Medical Professionals ◽  
Comprehensive Understanding ◽  
Novel Targets

The evolution of antifungal resistance among fungal pathogens has rendered the limited arsenal of antifungal drugs futile. Considering the recent rise in the number of nosocomial fungal infections in immunocompromised patients, the emerging clinical multidrug resistance (MDR) has become a matter of grave concern for medical professionals. Despite advances in therapeutic interventions, it has not yet been possible to devise convincing strategies to combat antifungal resistance. Comprehensive understanding of the molecular mechanisms of antifungal resistance is essential for identification of novel targets that do not promote or delay emergence of drug resistance. The present study discusses features and limitations of the currently available antifungals, mechanisms of antifungal resistance and highlights the emerging therapeutic strategies that could be deployed to combat MDR.

scholarly journals Prevalence and Therapeutic Challenges of Fungal Drug Resistance: Role for Plants in Drug Discovery

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 150 ◽  
Author(s):  
Lewis Marquez ◽  
Cassandra L. Quave
Keyword(s):  
United States ◽  
Drug Resistance ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Modern Medicine ◽  
Candida Auris ◽  
Medical Ethnobotany ◽  
Global Issue

Antimicrobial resistance is a global issue that threatens the effective practice of modern medicine and global health. The emergence of multidrug-resistant (MDR) fungal strains of Candida auris and azole-resistant Aspergillus fumigatus were highlighted in the Centers for Disease Control and Prevention’s (CDC) 2019 report, Antibiotic Resistance Threats in the United States. Conventional antifungals used to treat fungal infections are no longer as effective, leading to increased mortality. Compounding this issue, there are very few new antifungals currently in development. Plants from traditional medicine represent one possible research path to addressing the issue of MDR fungal pathogens. In this commentary piece, we discuss how medical ethnobotany—the study of how people use plants in medicine—can be used as a guide to identify plant species for the discovery and development of novel antifungal therapies.

scholarly journals Drug Repurposing in Medical Mycology: Identification of Compounds as Potential Antifungals to Overcome the Emergence of Multidrug-Resistant Fungi

2021 ◽  
Vol 14 (5) ◽  
pp. 488
Author(s):  
Lucie Peyclit ◽  
Hanane Yousfi ◽  
Jean-Marc Rolain ◽  
Fadi Bittar
Keyword(s):  
Opportunistic Infections ◽  
Fungal Infections ◽  
Drug Repurposing ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Medical Community ◽  
Medical Mycology ◽  
Candida Auris

Immunodepression, whether due to HIV infection or organ transplantation, has increased human vulnerability to fungal infections. These conditions have created an optimal environment for the emergence of opportunistic infections, which is concomitant to the increase in antifungal resistance. The use of conventional antifungal drugs as azoles and polyenes can lead to clinical failure, particularly in immunocompromised individuals. Difficulties related to treating fungal infections combined with the time required to develop new drugs, require urgent consideration of other therapeutic alternatives. Drug repurposing is one of the most promising and rapid solutions that the scientific and medical community can turn to, with low costs and safety advantages. To treat life-threatening resistant fungal infections, drug repurposing has led to the consideration of well-known and potential molecules as a last-line therapy. The aim of this review is to provide a summary of current antifungal compounds and their main resistance mechanisms, following by an overview of the antifungal activity of non-traditional antimicrobial drugs. We provide their eventual mechanisms of action and the synergistic combinations that improve the activity of current antifungal treatments. Finally, we discuss drug repurposing for the main emerging multidrug resistant (MDR) fungus, including the Candida auris, Aspergillus or Cryptococcus species.

scholarly journals On the emergence, spread and resistance of Candida auris: host, pathogen and environmental tipping points

2021 ◽  
Vol 70 (3) ◽  
Author(s):  
Arunaloke Chakrabarti ◽  
Prashant Sood
Keyword(s):  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Effective Management ◽  
Genetic Determinants ◽  
Candida Auris ◽  
Global Spread ◽  
Host Pathogen ◽  
Invasive Infections ◽  
High Level ◽  
Level Resistance

Over a decade ago, a multidrug-resistant nosocomial fungus Candida auris emerged worldwide and has since become a significant challenge for clinicians and microbiologists across the globe. A resilient pathogen, C. auris survives harsh disinfectants, desiccation and high-saline environments. It readily colonizes the inanimate environment, susceptible patients and causes invasive infections that exact a high toll. Prone to misidentification by conventional microbiology techniques, C. auris rapidly acquires multiple genetic determinants that confer multidrug resistance. Whole-genome sequencing has identified four distinct clades of C. auris, and possibly a fifth one, in circulation. Even as our understanding of this formidable pathogen grows, the nearly simultaneous emergence of its distinct clades in different parts of the world, followed by their rapid global spread, remains largely unexplained. We contend that certain host–pathogen–environmental factors have been evolving along adverse trajectories for the last few decades, especially in regions where C. auris originally appeared, until these factors possibly reached a tipping point to compel the evolution, emergence and spread of C. auris. Comparative genomics has helped identify several resistance mechanisms in C. auris that are analogous to those seen in other Candida species, but they fail to fully explain how high-level resistance rapidly develops in this yeast. A better understanding of these unresolved aspects is essential not only for the effective management of C. auris patients, hospital outbreaks and its global spread but also for forecasting and tackling novel resistant pathogens that might emerge in the future. In this review, we discuss the emergence, spread and resistance of C. auris, and propose future investigations to tackle this resilient pathogen.

scholarly journals Invasive Infections with Multidrug-Resistant Yeast Candida auris, Colombia

2017 ◽  
Vol 23 (1) ◽  
pp. 162-164 ◽  
Author(s):  
Soraya E. Morales-López ◽  
Claudia M. Parra-Giraldo ◽  
Andrés Ceballos-Garzón ◽  
Heidys P. Martínez ◽  
Gerson J. Rodríguez ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Candida Auris ◽  
Invasive Infections

scholarly journals The importance of rapid diagnosis for multidrug-resistant Candida: an interview with Maurizio Sanguinetti

2019 ◽  
Vol 14 (12) ◽  
pp. 1011-1012
Author(s):  
Maurizio Sanguinetti
Keyword(s):  
Infectious Diseases ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Resistance Mechanisms ◽  
Rapid Diagnosis ◽  
Antifungal Drugs ◽  
Full Professor ◽  
Research Activity ◽  
Diagnostic Strategies ◽  
Personalized Care

In this exclusive interview, Maurizio Sanguinetti discusses current issues with Candida fungal infection diagnoses, in light of its rising resistance to antifungal drugs. This interview was conducted by Ellen Colvin, Editor of Future Microbiology. Maurizio Sanguinetti, MD, is full Professor of Microbiology at the Università Cattolica del Sacro Cuore of Rome, Italy, and Director of the Institute of Microbiology and Chief of the Department of Laboratory Sciences and Infectious Diseases Sciences at the Fondazione Policlinico Agostino Gemelli IRCCS of Rome, Italy. For several years, the research activity of Maurizio Sanguinetti has mainly focused on the development of molecular methods for the rapid diagnosis of bacterial, mycobacterial and fungal infections; the elucidation of virulence and antimicrobial resistance mechanisms in clinically relevant bacterial and fungal pathogens; the characterization of the human microbiota in relationship to infectious and noninfectious diseases and implementation of new diagnostic strategies for the personalized care of patients with infectious diseases.

scholarly journals 2267. Epidemiology of Candida auris Candidemia in a Teaching Hospital in North of Oman: One-Year Survival

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S776-S776
Author(s):  
Arash Eatemadi ◽  
Aiman Al Wahibi ◽  
Hilal Al shibli ◽  
Ali Al reesi
Keyword(s):  
Public Health ◽  
Teaching Hospital ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Fungal Treatment ◽  
Candida Auris ◽  
Coagulase Negative Staphylococci ◽  
Central Public Health ◽  
Antibiotic Susceptibility Test ◽  
Recent Emergence

Abstract Background Recent emergence of Candida auris as a multidrug resistant fungal pathogen, is a serious concerns for public health. However, there is a paucity of reported cases from Oman. Literature search resulted in finding only 7 cases from Oman, reporting C. auris infections in the articles first published in 2017. However, the rate of isolatin is increasing. Methods In this study, we included the results of all positive blood cultures of C. auris in Suhar teaching hospital from May 2018 (date of first detection) till end of April 2019. Further confirmation of the species was performed by MALDI-TOF and antibiotic susceptibility test (AST) by Vitek 2 in central public health laboratory (CPHL) of Oman. Results We detected 13 patients (9 females, 4 males). The mean age was 58.61% years (28–76 years). All candidemic patients had serious underlying conditions, including prolonged hospital stay or extensive and prolonged antimicrobial exposure or medical comorbidities (8 of 13). The time from hospital admission to onset of C. auris candidemia was 8–49 days, with a median of approximately 27 days. The most common isolated co- pathogen from blood culture was K. pneumonia (without regard to Coagulase-negative staphylococci). As average, every patient received 4.8 kind of different antibiotics in mean 88 doses before candidemia developed and piperacillin–tazobactam was the most common used antibiotics. AST was done just for 5 patients and revealed high-level resistance to fluconazole and Amphotricin B while, Echinocandins (anidulafungin, caspofungin) were fully sensitive and voricunazole had intermediate sensitivity. Mean duration of anti-fungal treatment was 12.5 days (5 – 26 days). 8 patients treated by Echinocandins (4/8 died), 4 by Fluconazole (3/4 died) and one without treatment discharged. 30-day all-cause mortality was 61.5%. Conclusion In Oman, C. auris has been reported from many hospitals. Resistance to several antifungal agents and persistence in the hospital environment make this organism a potential menace for the treating physician and the infection control personnel. In our hospital, every candidemic patient should be treated with Echinocandins and assumed to be resistant to Fluconazole until proven otherwise according to results of AST. Disclosures All authors: No reported disclosures.

scholarly journals Emerging Fungal Infections: New Patients, New Patterns, and New Pathogens

2019 ◽  
Vol 5 (3) ◽  
pp. 67 ◽  
Author(s):  
Friedman ◽  
Schwartz
Keyword(s):  
North America ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Trichophyton Mentagrophytes ◽  
Invasive Fungal Disease ◽  
Multidrug Resistant ◽  
Antifungal Prophylaxis ◽  
Candida Spp ◽  
Sporothrix Brasiliensis ◽  
Emerging Fungal Infections

: The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans Candida spp., including C. auris, a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus Aspergillus species, Mucorales, and Scedosporium/Lomentospora spp. The agricultural application of triazole pesticides has driven an emergence of azole-resistant A. fumigatus in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in Trichophyton mentagrophytes causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including Emergomyces, which cause disseminated mycoses globally, primarily in HIV infected patients, and Blastomyces helicus and B. percursus, causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by Sporothrix brasiliensis has emerged as an important disease of felines and people.

scholarly journals Candida auris: a fungus with identity crisis

2020 ◽  
Vol 78 (4) ◽  
Author(s):  
Taissa Vila ◽  
Ahmed S Sultan ◽  
Daniel Montelongo-Jauregui ◽  
Mary Ann Jabra-Rizk
Keyword(s):  
Fungal Species ◽  
Antifungal Drugs ◽  
Multiple Drug ◽  
Rapid Diagnostics ◽  
Contributing Factors ◽  
Candida Auris ◽  
Healthcare Facilities ◽  
Drug Classes ◽  
Recent Emergence ◽  
Robust Response

ABSTRACT Candida auris is a new fungal species that has puzzlingly and simultaneously emerged on five continents. Since its identification in 2009, the scientific community has witnessed an exponential emergence of infection episodes and outbreaks in healthcare facilities world-wide. Candida auris exhibits several concerning features compared to other related Candida species, including persistent colonization of skin and nosocomial surfaces, ability to resist common disinfectants and to spread rapidly among patients. Resistance to multiple drug classes and misidentification by available laboratory identification systems has complicated clinical management, and outcomes of infection have generally been poor with mortality rates approaching 68%. Currently, the origins of C. auris are unclear, and therefore, it is impossible to determine whether environmental and climactic changes were contributing factors in its recent emergence as a pathogen. Nevertheless, a robust response involving rapid diagnostics, prompt interventions and implementation of precautions, are paramount in curtailing the spread of  infections by this fungal species. Importantly, there is a pressing need for the development of new antifungal drugs. In this article, we present a brief overview highlighting some of the important aspects of C. auris epidemiology, pathogenesis and its puzzling global emergence.

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