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Antifungal Medications

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1. Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi Full Text available with Trip Pro

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

2017 Mediators of inflammation

2. Genome-wide elucidation of drug resistance mechanisms for systemically used antifungal drugs amphotericin B, caspofungin and voriconazole in the budding yeast. Full Text available with Trip Pro

Genome-wide elucidation of drug resistance mechanisms for systemically used antifungal drugs amphotericin B, caspofungin and voriconazole in the budding yeast. There are only a few systemically used antifungal drugs in the treatment, and invasive fungal infections that are resistant to these drugs are an emerging problem in healthcare. In this study, we performed a high copy genomic DNA (gDNA) library screening to find and characterize genes that reduce susceptibility to amphotericin B (...) expression patterns of the cells after treatment with the antifungals and determined the genes and paths that are up or down-regulated. We also cloned Candida albicans homologs of PDR16, PMP3, MRS3 and TRI1 genes and expressed them in S. cerevisiae. Heterologous expression of Candida homologs also provided reduced drug susceptibility to the budding yeast cells. Our analyses suggest the involvement of new genes in the antifungal drug resistance.Copyright © 2019 American Society for Microbiology.

2019 Antimicrobial Agents and Chemotherapy

3. Antifungal therapy: drug-drug interactions at your fingertips. Full Text available with Trip Pro

clinical significance. Specifically, successful treatment with antifungal agents is complicated by the high potential to interact with other concomitant medications. We describe here the development of a real-time knowledge base of DDIs with antifungal agents, providing expert recommendations to HCPs on how to handle DDIs with these drugs. This new resource will facilitate rapid identification, quantification and classification of these DDIs by clinicians with varying levels of experience and resources (...) Antifungal therapy: drug-drug interactions at your fingertips. The Information Age has revolutionized the ability of healthcare professionals (HCPs) to oversee a substantial body of clinically relevant information literally at one's fingertips. In the field of clinical pharmacology, this may be particularly useful for managing drug-drug interactions (DDIs). A thorough understanding of the underlying mechanisms of DDIs allows the HCP to predict such interactions and avoid those of greatest

2015 Journal of Antimicrobial Chemotherapy

4. D-Index-Guided Early Antifungal Therapy Versus Empiric Antifungal Therapy for Persistent Febrile Neutropenia: A Randomized Controlled Noninferiority Trial

of Medicine, Sapporo, Japan. 16 Department of Hematology, Tokyo Medical University, Tokyo, Japan. 17 Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. 18 General Medical Research Center, Fukuoka University, Fukuoka, Japan. PMID: 31977270 DOI: Item in Clipboard Full-text links Cite Abstract Purpose: Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN), but in most patients (...) , decreased the use and cost of antifungal agents without increasing invasive fungal infections and can be a reasonable alternative to empiric or preemptive antifungal therapy. Similar articles Moen MD, Lyseng-Williamson KA, Scott LJ. Moen MD, et al. Drugs. 2009;69(3):361-92. doi: 10.2165/00003495-200969030-00010. Drugs. 2009. PMID: 19275278 Review. Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, Dhédin N, Isnard F, Ades L, Kuhnowski F, Foulet F, Kuentz M, Maison P, Bretagne S

2020 EvidenceUpdates

5. Fabrication of a drug delivery system that enhances antifungal drug corneal penetration Full Text available with Trip Pro

Fabrication of a drug delivery system that enhances antifungal drug corneal penetration Fungal keratitis (FK) remains a severe eye disease, and effective therapies are limited by drug shortages and critical ocular barriers. Despite the high antifungal potency and broad spectrum of econazole, its strong irritant and insolubility in water hinder its ocular application. We designed and fabricated a new drug delivery system based on a polymeric vector for the ocular antifungal application (...) of econazole. This novel system integrates the advantages of its constituent units and exhibits superior comprehensive performance. Using the new system, drug content was significantly increased more than 600 folds. The results of in vivo and in vitro experiments demonstrated that the econazole-loaded formulation exhibited significantly enhanced corneal penetration after a single topical ocular administration, excellent antifungal activity, and good tolerance in rabbits. Drug concentrations and ocular

2018 Drug delivery

6. Screening a Repurposing Library for Inhibitors of Multi-Drug Resistant <i>Candida auris</i> Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development. Full Text available with Trip Pro

Screening a Repurposing Library for Inhibitors of Multi-Drug Resistant Candida auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development. Since its original isolation in 2009, Candida auris has spread across the globe as a causative agent of invasive candidiasis. C. auris is typically intrinsically resistant to fluconazole and can also be resistant to echinocandins and even amphotericin B. Thus, there is an urgent need to find new treatment options against (...) . auris Confirmation and follow-up studies identified ebselen as the drug displaying the most potent activity, with 100% inhibition of growth detected at concentrations as low as 2.5 μM. We further evaluated the ability of ebselen to inhibit C. auris biofilm formation and examined the effects of combination therapies of ebselen with clinically used antifungals. We extended our studies to different C. auris strains with various susceptibility patterns and also confirmed its antifungal activity against

2018 Antimicrobial Agents and Chemotherapy

7. Increasing prevalence, molecular characterization and antifungal drug susceptibility of serial Candida auris isolates in Kuwait. Full Text available with Trip Pro

Increasing prevalence, molecular characterization and antifungal drug susceptibility of serial Candida auris isolates in Kuwait. Candida auris is an emerging yeast pathogen of global significance. Its multidrug-resistant nature and inadequacies of conventional identification systems pose diagnostic and therapeutic challenges. This study investigated occurrence of C. auris in clinical specimens in Kuwait and its susceptibility to antifungal agents. Clinical yeast strains isolated during 3.5-year (...) period and forming pink-colored colonies on CHROMagar Candida were studied by wet mount examination for microscopic morphology and Vitek 2 yeast identification system. A simple species-specific PCR assay was developed for molecular identification and results were confirmed by PCR-sequencing of rDNA. Antifungal susceptibility testing of one isolate from each patient was determined by Etest. The 280 isolates forming pink-colored colonies on CHROMagar Candida, were identified by Vitek 2 as Candida

2018 PLoS ONE

8. Editorial: Antifungal Drug Discovery: New Theories and New Therapies Full Text available with Trip Pro

Editorial: Antifungal Drug Discovery: New Theories and New Therapies 27242745 2016 05 31 2018 11 13 1664-302X 7 2016 Frontiers in microbiology Front Microbiol Editorial: Antifungal Drug Discovery: New Theories and New Therapies. 728 10.3389/fmicb.2016.00728 Seneviratne Chaminda J CJ Faculty of Dentistry, National University of Singapore Singapore, Singapore. Rosa Edvaldo A R EA The Pontifical Catholic University of Paraná Curitiba, Brazil. eng Journal Article 2016 05 23 Switzerland Front (...) Microbiol 101548977 1664-302X Candida albicans Candida biofilms antifungals new drug discovery oral candidiasis 2016 03 16 2016 05 02 2016 6 1 6 0 2016 6 1 6 0 2016 6 1 6 1 epublish 27242745 10.3389/fmicb.2016.00728 PMC4876608 N Engl J Med. 2015 Oct 8;373(15):1445-56 26444731 Drugs. 2009;69 Suppl 1:5-14 19877728 Crit Rev Microbiol. 2011 Nov;37(4):328-36 21777047 Drug Discov Today. 2014 Nov;19(11):1721-30 24952336 J Antimicrob Chemother. 2011 Mar;66(3):457-65 21172787 Cold Spring Harb Perspect Med. 2014

2016 Frontiers in microbiology

9. <i>Candida auris</i>: a comparison between planktonic and biofilm susceptibility to antifungal drugs. (Abstract)

Candida auris: a comparison between planktonic and biofilm susceptibility to antifungal drugs. Introduction.Candida auris is a pathogenic yeast that mainly affects immunosuppressed patients and those with implanted medical devices. This pathogen also displays elevated resistance to common antifungals and high survival and spreading capacities. Since no antifungal breakpoints have yet been defined for this pathogen, the data obtained here can be useful for further research concerning (...) , and the results were compared with those obtained for Candida albicans and Candida parapsilosis, two species strongly linked to bloodstream infections and infections associated with biomaterials. We found that the clinical isolates of C. auris were resistant to fluconazole and sensitive to echinocandins and polyenes. The C. auris biofilms did not show susceptibility to any antifungal agent, showing MBECs that were up to 512-fold higher than the MICs. These findings highlight the importance of biofilm

2019 Journal of Medical Microbiology

10. Multicentre study to determine the Etest epidemiological cut-off values of antifungal drugs in Candida spp. and Aspergillus fumigatus species complex. Full Text available with Trip Pro

Multicentre study to determine the Etest epidemiological cut-off values of antifungal drugs in Candida spp. and Aspergillus fumigatus species complex. To determine the Etest-based epidemiological cut-off values (ECVs) for antifungal agents against the most frequent yeast and Aspergillus fumigatus species isolated in 12 French hospitals.For each antifungal agent, the Etest MICs in yeast and A. fumigatus isolates from 12 French laboratories were retrospectively collected from 2004 to 2018 (...) instead of breakpoints, but may be useful to identify non-wild-type isolates with potential resistance to antifungal agents, and to indicate that an isolate may not respond as expected to the standard treatment.Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

2019 Clinical Microbiology and Infection

11. A First-in-Human Phase 1 Study to Assess Safety, Tolerability and Pharmacokinetics of a Novel Antifungal Drug VL-2397 in Healthy Adults. (Abstract)

A First-in-Human Phase 1 Study to Assess Safety, Tolerability and Pharmacokinetics of a Novel Antifungal Drug VL-2397 in Healthy Adults. VL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal in vitro activity, and potent in vivo activity against Aspergillus fumigatus, including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study was conducted in healthy adults to determine the safety (...) , tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous (IV) doses of VL-2397. All dosing cohorts were fully enrolled; all subjects completed the safety follow-up. A safety committee reviewed the safety data for each dosing cohort prior to recommending the initiation of each subsequent cohort. No serious adverse events (SAEs) occurred; the majority of treatment-emergent adverse events (TEAEs) were mild and self-limited. The most common drug-related TEAEs were infusion site

2019 Antimicrobial Agents and Chemotherapy Controlled trial quality: uncertain

12. Detection of <i>Candida auris</i> antifungal drug resistance markers directly from clinical skin swabs. (Abstract)

Detection of Candida auris antifungal drug resistance markers directly from clinical skin swabs. Accurate and rapid assessment of Candida auris antifungal drug resistance is crucial for effective infection prevention and control actions, and patient management. Here, performance of a molecular diagnostic platform, enabling rapid identification of FKS1 and ERG11 mutations conferring echinocandin and azole resistance, respectively, was evaluated on a panel of clinical skin swabs. Gene (...) sequencing and antifungal susceptibility testing were used as "gold standard". All swabs were correctly categorized as harboring wild-type or mutant C. auris.Copyright © 2019 American Society for Microbiology.

2019 Antimicrobial Agents and Chemotherapy

13. ANTIFUNGAL DRUGS INFLUENCE NEUTROPHIL EFFECTOR FUNCTIONS. Full Text available with Trip Pro

ANTIFUNGAL DRUGS INFLUENCE NEUTROPHIL EFFECTOR FUNCTIONS. Introduction: There is a growing body of evidence for immunomodulatory side effects of antifungal agents on different immune cells e.g. in T cells. Therefore, the aim of our study is to clarify these interactions with regard to the effector functions of polymorphonuclear neutrophils (PMN).Methods: Human PMN were preincubated with fluconazole (FLC), voriconazole (VRC), posaconazole (POS), isavuconazole (ISA), caspofungin (CAS), micafungin (...) decreased activation signaling, impaired degranulation, and lower generation of ROS. MFG caused enhanced expression of activation marker but impaired degranulation, phagocytosis, generation of ROS, and IL-8 release. CAS showed an increased phagocytosis, whereas degranulation and generation of ROS were reduced by trend. AMB led to activation of almost all effector functions besides impaired phagocytosis, whereas LAMB did not alter any effector functions.Conclusions: Independent from class, antifungal

2019 Antimicrobial Agents and Chemotherapy

14. Improved Methods for Assessing Therapeutic Potential of Antifungal Agents Against Dermatophytes and their Application in the Development of NP213, a Novel Onychomycosis Therapy Candidate. Full Text available with Trip Pro

Improved Methods for Assessing Therapeutic Potential of Antifungal Agents Against Dermatophytes and their Application in the Development of NP213, a Novel Onychomycosis Therapy Candidate. Onychomycosis is a common, difficult to treat nail infection, mainly caused by dermatophytes. Current therapies are not wholly effective and are associated with manifold side effects. The development of treatments for onychomycosis is challenging because standard in vitro tests are not predictive of antifungal (...) within the nail. To address that, we present a more physiologically relevant modified AST method. This method, alongside other standard in vitro assessments of activity (including mechanism of action and time of kill studies) better reflected the activity of NP213 and other antifungal agents within the nail than standard in vitro AST methods. NP213 is a rapidly acting, fungicidal peptide, superior to existing antifungal agents in vitro It penetrated the nail more effectively than other antifungals

2019 Antimicrobial Agents and Chemotherapy

15. Antifungal prophylaxis in pediatric patients undergoing therapy for cancer: drugs and dosing. (Abstract)

Antifungal prophylaxis in pediatric patients undergoing therapy for cancer: drugs and dosing. Invasive fungal disease (IFD) is an important cause of morbidity and mortality in immunocompromised patients. In contrast to adults, detailed information of pharmacokinetics and pharmacodynamics of many antifungal compounds is lacking in pediatric patients, and antifungal agents that have been proven to be effective in adults have not been licensed for children. We therefore review the current (...) literature on drugs and dosing for antifungal prophylaxis in the pediatric age group.Although there are only few compounds approved for antifungal prophylaxis in children, an increasing number of reports describe safety and suggest efficacy of agents given to prevent IFD in the pediatric population. Owing to the small number of children included in most studies, however, evidence for efficacy has to be extrapolated from studies in adults. In addition, most studies do not address the optimal dosage

2015 Current Opinion in Infectious Diseases

16. Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent Full Text available with Trip Pro

Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified.This investigation compares bee venom in its whole and partial forms to evaluate the possible component (...) responsible for the antifungal effect.Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies.The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM

2018 Annals of dermatology

17. Topical and systemic antifungal therapy for chronic rhinosinusitis. Full Text available with Trip Pro

Topical and systemic antifungal therapy for chronic rhinosinusitis. This review adds to a series of reviews looking at primary medical management options for patients with chronic rhinosinusitis.Chronic rhinosinusitis is common and characterised by inflammation of the lining of the nose and paranasal sinuses leading to nasal blockage, nasal discharge, facial pressure/pain and loss of sense of smell. The condition can occur with or without nasal polyps. Antifungals have been suggested (...) as a treatment for chronic rhinosinusitis.To assess the effects of systemic and topical antifungal agents in patients with chronic rhinosinusitis, including those with allergic fungal rhinosinusitis (AFRS) and, if possible, AFRS exclusively.The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished

2018 Cochrane

18. <i>In vitro</i> and <i>in vivo</i> assessment of FK506 analogs as novel antifungal drug candidates. Full Text available with Trip Pro

In vitro and in vivo assessment of FK506 analogs as novel antifungal drug candidates. FK506 (tacrolimus) is an FDA-approved immunosuppressant indicated for the prevention of allograft rejections in patients undergoing organ transplants. In mammals, FK506 inhibits the calcineurin-nuclear factor of activated T cells (NFAT) pathway to prevent T-cell proliferation by forming a ternary complex with its binding protein, FKBP12, and calcineurin. FK506 also exerts antifungal activity (...) by inhibiting calcineurin, which is essential for the virulence of human-pathogenic fungi. Nevertheless, FK506 cannot be used directly as an antifungal drug due to its immunosuppressive action. In this study, we analyzed the cytotoxicity, immunosuppressive activity, and antifungal activity of four FK506 analogs, 31-O-demethyl-FK506, 9-deoxo-FK506, 9-deoxo-31-O-demethyl-FK506, and 9-deoxo-prolyl-FK506, in comparison with that of FK506. The four FK506 analogs generally possessed lower cytotoxicity

2018 Antimicrobial Agents and Chemotherapy

19. Dysfunction of Prohibitin 2 Results in Reduced Susceptibility to Multiple Antifungal Drugs via Activating the Oxidative Stress Responsive Transcription Factor Pap1 in Fission Yeast. Full Text available with Trip Pro

Dysfunction of Prohibitin 2 Results in Reduced Susceptibility to Multiple Antifungal Drugs via Activating the Oxidative Stress Responsive Transcription Factor Pap1 in Fission Yeast. The fight against resistance to antifungal drugs requires a better understanding of the underlying cellular mechanisms. In order to gain insight into the mechanisms leading to antifungal drug resistance, we performed a genetic screen on a model organism, Schizosaccharomyces pombe, to identify genes whose (...) overexpression caused resistance to antifungal drugs, including clotrimazole and terbinafine. We identified the phb2+ gene, encoding a highly conserved mitochondrial protein, prohibitin (Phb2), as a novel determinant of reduced susceptibility to multiple antifungal drugs. Unexpectedly, deletion of the phb2+ gene also exhibited antifungal drug resistance. Overexpression of the phb2+ gene failed to cause drug resistance when the pap1+ gene, encoding an oxidative stress-responsive transcription factor

2018 Antimicrobial Agents and Chemotherapy

20. Reliable and easy-to-use Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) assay for quantification of Olorofim (F901318) - a novel antifungal drug - in human plasma and serum. Full Text available with Trip Pro

Reliable and easy-to-use Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) assay for quantification of Olorofim (F901318) - a novel antifungal drug - in human plasma and serum. A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, olorofim (F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated. Sample preparation was based on protein (...) electrospray ionization (HESI+) within a single runtime of 2.00 min. The present LC-MS/MS method was validated according to the international guidelines of the International Conference on Harmonisation (ICH) and the U.S. Food and Drug Administration (FDA). Linearity of F901318 concentration ranges was verified by the Mandel test. The calibration curve was tested linear across the range and fitted using least-squares regression with a weighting factor of the reciprocal concentration. The limit of detection

2018 Antimicrobial Agents and Chemotherapy

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