scholarly journals Rare fungal infectious agents: a lurking enemy

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1917 ◽  
Author(s):  
Anna Skiada ◽  
Ioannis Pavleas ◽  
Maria Drogari-Apiranthitou
Keyword(s):  
De Novo ◽  
Direct Detection ◽  
Fungal Infections ◽  
Molecular Techniques ◽  
Antifungal Drugs ◽  
Diagnostic Methods ◽  
High Morbidity ◽  
Infectious Agents ◽  
Dimorphic Fungi ◽  
Invasive Infections

In the expanding population of immunocompromised patients and those treated in intensive care units, rare fungal infectious agents have emerged as important pathogens, causing invasive infections associated with high morbidity and mortality. These infections may present either asde novoor as breakthrough invasive infections in high-risk patients with hematologic malignancies receiving prophylactic or empirical antifungal therapy or in patients with central venous catheters. Diagnosis and treatment are challenging. Physicians should have a high index of suspicion because early diagnosis is of paramount importance. Conventional diagnostic methods such as cultures and histopathology are still essential, but rapid and more specific molecular techniques for both detection and identification of the infecting pathogens are being developed and hopefully will lead to early targeted treatment. The management of invasive fungal infections is multimodal. Reversal of risk factors, if feasible, should be attempted. Surgical debridement is recommended in localized mold infections. The efficacy of various antifungal drugs is not uniform. Amphotericin B is active against most yeasts, exceptTrichosporon, as well as againstMucorales,Fusarium, and some species ofPaecilomycesand dimorphic fungi. The use of voriconazole is suggested for the treatment of trichosporonosis and scedosporiosis. Combination treatment, though recommended as salvage therapy in some infections, is controversial in most cases. Despite the use of available antifungals, mortality remains high. The optimization of molecular-based techniques, with expansion of reference libraries and the possibility for direct detection of resistance mechanisms, is awaited with great interest in the near future. Further research is necessary, however, in order to find the best ways to confront and destroy these lurking enemies.

scholarly journals Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 445 ◽  
Author(s):  
Gina Wall ◽  
Jose L. Lopez-Ribot
Keyword(s):  
Drug Development ◽  
Drug Interactions ◽  
Fungal Infections ◽  
Mortality Rates ◽  
Clinical Development ◽  
Antifungal Drugs ◽  
High Morbidity ◽  
Eukaryotic Organisms ◽  
Emergence Of Resistance ◽  
Compromised Patients

Fungal infections represent an increasing threat to a growing number of immune- and medically compromised patients. Fungi are eukaryotic organisms and, as such, there is a limited number of selective targets that can be exploited for antifungal drug development. This has also resulted in a very restricted number of antifungal drugs that are clinically available for the treatment of invasive fungal infections at the present time—polyenes, azoles, echinocandins, and flucytosine. Moreover, the utility of available antifungals is limited by toxicity, drug interactions and the emergence of resistance, which contribute to high morbidity and mortality rates. This review will present a brief summary on the landscape of current antifungals and those at different stages of clinical development. We will also briefly touch upon potential new targets and opportunities for novel antifungal strategies to combat the threat of fungal infections.

scholarly journals COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?

2020 ◽  
Vol 6 (4) ◽  
pp. 211 ◽  
Author(s):  
Amir Arastehfar ◽  
Agostinho Carvalho ◽  
M. Hong Nguyen ◽  
Mohammad Taghi Hedayati ◽  
Mihai G. Netea ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Molecular Techniques ◽  
Antifungal Drugs ◽  
Diagnostic Tools ◽  
Candida Spp ◽  
Comparative Performance ◽  
Number Of Patients ◽  
Clinical Awareness

The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. Candida species are major constituents of the human mycobiome and the main cause of invasive fungal infections, with a high mortality rate. Invasive yeast infections (IYIs) are increasingly recognized as s complication of severe COVID-19. Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to Candida. This suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVID-19 patients to develop IYIs. Although data on the comparative performance of diagnostic tools are often lacking in COVID-19 patients, a combination of serological and molecular techniques may present a promising option for the identification of IYIs. Clinical awareness and screening are needed, as IYIs are difficult to diagnose, particularly in the setting of severe COVID-19. Echinocandins and azoles are the primary antifungal used to treat IYIs, yet the therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata call for the development of new antifungal drugs with novel mechanisms of action.

scholarly journals Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Juliana Alves Parente-Rocha ◽  
Alexandre Melo Bailão ◽  
André Correa Amaral ◽  
Carlos Pelleschi Taborda ◽  
Juliano Domiraci Paccez ◽  
...  
Keyword(s):  
Drug Targets ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Public Health Problem ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Immunocompromised Patients ◽  
Dimorphic Fungi ◽  
Novel Drug ◽  
Novel Drug Targets

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs.

scholarly journals CandidaInfections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Spampinato ◽  
Darío Leonardi
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Diagnostic Methods ◽  
Opportunistic Pathogens ◽  
Yeast Infection ◽  
Life Threatening ◽  
Therapeutic Alternatives

The genusCandidaincludes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised.Candidainfections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genusCandidaand yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment ofCandidainfections is also provided.

scholarly journals Raman Imaging of Pathogenic Candida auris: Visualization of Structural Characteristics and Machine-Learning Identification

2021 ◽  
Vol 12 ◽  
Author(s):  
Giuseppe Pezzotti ◽  
Miyuki Kobara ◽  
Tenma Asai ◽  
Tamaki Nakaya ◽  
Nao Miyamoto ◽  
...  
Keyword(s):  
Machine Learning ◽  
Raman Spectroscopy ◽  
Fungal Infections ◽  
Structural Characteristics ◽  
Drug Efficacy ◽  
Antifungal Drugs ◽  
High Morbidity ◽  
Clinical Environment ◽  
Candida Auris ◽  
Immunosuppressed Patients

Invasive fungal infections caused by yeasts of the genus Candida carry high morbidity and cause systemic infections with high mortality rate in both immunocompetent and immunosuppressed patients. Resistance rates against antifungal drugs vary among Candida species, the most concerning specie being Candida auris, which exhibits resistance to all major classes of available antifungal drugs. The presently available identification methods for Candida species face a severe trade-off between testing speed and accuracy. Here, we propose and validate a machine-learning approach adapted to Raman spectroscopy as a rapid, precise, and labor-efficient method of clinical microbiology for C. auris identification and drug efficacy assessments. This paper demonstrates that the combination of Raman spectroscopy and machine learning analyses can provide an insightful and flexible mycology diagnostic tool, easily applicable on-site in the clinical environment.

scholarly journals Equine endometritis: a review of challenges and new approaches

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. R95-R110
Author(s):  
Lee H A Morris ◽  
P M McCue ◽  
Christine Aurich
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Fungal Infections ◽  
Immunological Response ◽  
Diagnostic Methods ◽  
Infectious Agents ◽  
Latent Infections ◽  
New Approaches ◽  
Targeted Treatments ◽  
Successful Resolution

Endometritis in the mare begins as a normal physiological inflammatory response to breeding that involves both a mechanical and immunological response pathway activated to rid the uterus of semen and bacteria. With successful resolution of this inflammation, the mare‘s uterus will provide a hospitable environment for the development of the semi-allogenic conceptus. If the mare fails to resolve this inflammatory response within 48 h of breeding, she will become susceptible to persistent breeding-induced endometritis (PBIE) which will have detrimental effects on her fertility. This condition can then predispose the mare to bacterial or fungal endometritis leading to further degeneration of the endometrium. Optimisation of the mare’s fertility requires a fine balance between allowing the natural immune response of the endometrium to its exposure to allogenic semen to run its course, and yet preventing its progression to PBIE or the involvement of infectious agents. This review discusses the challenges presented by PBIE, latent infections, biofilms, fungal infections and the need to utilise diagnostic methods available and implement targeted treatments to optimise fertility in the mare.

scholarly journals The Use of Galleria mellonella Larvae to Identify Novel Antimicrobial Agents against Fungal Species of Medical Interest

2018 ◽  
Vol 4 (3) ◽  
pp. 113 ◽  
Author(s):  
Kevin Kavanagh ◽  
Gerard Sheehan
Keyword(s):  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Fungal Infections ◽  
Fungal Species ◽  
Molecular Techniques ◽  
Antifungal Drugs ◽  
Immune Priming ◽  
Greater Wax Moth

The immune system of insects and the innate immune response of mammals share many similarities and, as a result, insects may be used to assess the virulence of fungal pathogens and give results similar to those from mammals. Larvae of the greater wax moth Galleria mellonella are widely used in this capacity and also for assessing the toxicity and in vivo efficacy of antifungal drugs. G. mellonella larvae are easy to use, inexpensive to purchase and house, and have none of the legal/ethical restrictions that are associated with use of mammals. Larvae may be inoculated by intra-hemocoel injection or by force-feeding. Larvae can be used to assess the in vivo toxicity of antifungal drugs using a variety of cellular, proteomic, and molecular techniques. Larvae have also been used to identify the optimum combinations of antifungal drugs for use in the treatment of recalcitrant fungal infections in mammals. The introduction of foreign material into the hemocoel of larvae can induce an immune priming effect which may operate independently with the activity of the antifungal drug. Procedures to identify this effect and limit its action are required.

scholarly journals Striking Back against Fungal Infections: The Utilization of Nanosystems for Antifungal Strategies

2021 ◽  
Vol 22 (18) ◽  
pp. 10104
Author(s):  
Wei Du ◽  
Yiru Gao ◽  
Li Liu ◽  
Sixiang Sai ◽  
Chen Ding
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Water Solubility ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Aspergillus Species ◽  
Health Concern ◽  
Tissue Penetration ◽  
Major Health ◽  
Invasive Infections

Fungal infections have become a major health concern, given that invasive infections by Candida, Cryptococcus, and Aspergillus species have led to millions of mortalities. Conventional antifungal drugs including polyenes, echinocandins, azoles, allylamins, and antimetabolites have been used for decades, but their limitations include off-target toxicity, drug-resistance, poor water solubility, low bioavailability, and weak tissue penetration, which cannot be ignored. These drawbacks have led to the emergence of novel antifungal therapies. In this review, we discuss the nanosystems that are currently utilized for drug delivery and the application of antifungal therapies.

scholarly journals The role of chest ultrasound in diagnosing invasive fungal infections in acute leukemia patients

2016 ◽  
Vol 11 (2) ◽  
pp. 132-137
Author(s):  
Ana-Maria NEAGU ◽  
◽  
Ana-Maria VLĂDĂREANU ◽  
Horia BUMBEA ◽  
Diana CÎŞLEANU ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Fungal Infections ◽  
Low Cost ◽  
Empirical Therapy ◽  
Invasive Fungal Infections ◽  
Diagnostic Methods ◽  
High Morbidity ◽  
Non Invasive ◽  
Chest Ultrasound

Acute leukemia patients are the category of highest risk to develop invasive fungal infections, have high morbidity and mortality rates related to these complications. The diagnosis of these infections must be accurate and early. That is the main reason for searching non-invasive, fast, available and low cost diagnostic methods. Imagistic diagnosis is essential, computer tomography is the gold standard. Chest ultrasound has most of these characteristics, offers valuable informations and they are accurate when compared to the chest tomography results. The decision to initiate antifungal therapy is significantly better than the empirical therapy, having lower mortality rate among these patients.

The antifungal activities and biological consequences of BMVC-12C-P, a carbazole derivative against Candida species

2019 ◽  
Vol 58 (4) ◽  
pp. 521-529
Author(s):  
Mandy Shen ◽  
Pei-Tzu Li ◽  
Yan-Jia Wu ◽  
Ching-Hsuan Lin ◽  
Eric Chai ◽  
...  
Keyword(s):  
Candida Species ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
New Drugs ◽  
High Morbidity ◽  
Carbazole Derivative ◽  
Antifungal Activities ◽  
Development Of Resistance ◽  
Fluconazole Resistant ◽  
Candida Infections

Abstract Fungal infections, particularly Candida species, have increased worldwide and caused high morbidity and mortality rates. The toxicity and development of resistance in present antifungal drugs justify the need of new drugs with different mechanism of action. BMVC-12C-P, a carbazole-type compound, has been found to dysfunction mitochondria. BMVC-12C-P displayed the strongest antifungal activities among all of the BMVC derivatives. The minimal inhibitory concentration (MIC) of BMVC-12C-P against Candida species ranged from 1 to 2 μg/ml. Fluconazole-resistant clinical isolates of Candida species were highly susceptible to BMVC-12C-P. The potent fungicidal activity of BMVC-12C-P relates to its impairing mitochondrial function. Furthermore, we found that the hyphae growth and biofilm formation were suppressed in C. albicans survived from BMVC-12C-P treatment. This study demonstrates the potential of BMVC-12C-P as an antifungal agent for treating Candida infections.

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