Identification of off-patent drugs that show synergism with Amphotericin B or that present antifungal action against Cryptococcus neoformans and Candida spp.

Identification of off-patent drugs that show synergism with Amphotericin B or that present antifungal action against Cryptococcus neoformans and Candida spp. Antimicrob Agents Chemother. 2020 Jan 27;: Authors: Rossi SA, de Oliveira HC, Agreda-Mellon D, Lucio J, Mendes Giannini MJS, García-Cambero JP, Zaragoza O Abstract Amphotericin B (AmB) is the antifungal with the strongest fungicidal activity, but its use has several limitations, mainly associated to its toxicity. Although some lipidic and liposomal formulations that present reduced toxicity are available, their price limits their application in developing countries. Flucytosine (FC) has shown synergistic effect with AmB for treatment of some fungal infections, such as cryptococcosis, but again, its price is a limitation for its use in many regions. In the present work, we aimed to identify new drugs that having a minor effect on C. neoformans, reduced its growth in the presence of sub-inhibitory concentrations of AmB. In the initial screening, we found fourteen drugs that had this pattern. Later, checkerboard assays of selected compounds such as erythromycin, riluzole, nortriptyline, chenodiol, nisoldipine, promazine, chlorcyclizine, cloperastine and glimepiride, were performed and all of them confirmed for their synergistic effect (FICI
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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We investigated the characteristics and associated factors of invasive fungal disease in patients with type  2 diabetes mellitus from Southern China for the first time. We found thatCandida albicans,Cryptococcus neoformans andAspergillus fumigatus were the leading agents. Prolonged hyperglycemia results in unfavorable outcomes. Correction of anemia and hypoalbuminemia might improve prognosis. AbstractAims/IntroductionA retrospective study was carried out to investigate the clinical characteristics and associated factors for invasive fungal disease in patients with type  2 diabetes mellitus.Materials and MethodsDe...
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Original Article Source Type: research
AbstractObjectivesA retrospective study was performed to investigate the clinical characteristics and associated factors for invasive fungal disease (IFD) in patients with type 2 diabetes mellitus (T2DM).MethodsDemographic and clinical data were recorded. Associated factors were analyzed by logistic regression analysis.ResultsIFD was diagnosed in 120 patients with T2DM (prevalence, 0.4%). Yeast infection (56/120, 46.7%), including candidiasis (31/56, 55.4%) and cryptococcosis (25/56, 44.6%) was the most common. Urinary tract was mainly involved in candidiasis (12/31, 38.7%). More than half of the cryptococcosis (16/25, 64....
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: ORIGINAL ARTICLE Source Type: research
CONCLUSIONS: In this single-center series of liver transplant recipients, the incidence of invasive fungal infections was relatively low, probably due to the universal prophylaxis with fluconazole and limited use of the broad-spectrum antibiotics. Early diagnosis and treatment of invasive fungal infections could lead to a better prognosis for liver transplant recipients with invasive fungal infections. PMID: 31724926 [PubMed - as supplied by publisher]
Source: Experimental and Clinical Transplantation : official journal of the Middle East Society for Organ Transplantation - Category: Transplant Surgery Authors: Tags: Exp Clin Transplant Source Type: research
Abstract Fungal infections are an important cause of morbidity and mortality in renal transplant recipients. These infections account for 5% of all infections in renal transplant recipients. The symptoms of systemic fungal infections are nonspecific, particularly in their early stages, and this can lead to delay in diagnosis. Retrospective analysis was conducted on all renal transplants that were performed at our center over a 20-year period from 1996-2016. Cases of invasive fungal infections (IFIs) that occurred among renal transplant recipients were identified to describe the epidmeiology of these infections. A ...
Source: Saudi Journal of Kidney Diseases and Transplantation - Category: Urology & Nephrology Authors: Tags: Saudi J Kidney Dis Transpl Source Type: research
Conclusion and Perspectives CYP51 plays a crucial role in fungal invasive growth, hyphae formation and virulence, and inhibitors targeting CYP51 have always been an important component of antifungal agents. Further researches on fungal CYP51s might set about from the following aspects: First, while the detailed crystal structures of several susceptible pathogenic fungi CYP51 have been elaborated, those of drug-resistant variants are still in hypothesis. If those structures were elucidated, targeting at common drug-resistant CYP51 protein variants could probably be promising. Second, it deserves more in-depth researches to...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study they also showed PTX3 localized in NETs formed after neutrophil activation (5). Proteomics analysis revealed that PTX3 forms complexes with two anti-microbial proteins [azurocidin (AZU1) and myeloperoxidase (MPO)] associated to NETs (30). More recently, PTX3 localization in NETs has been confirmed, and the colocalization with AZU1 and MPO has been defined more accurately (31). Further investigation will be needed to understand the involvement of PTX3 interaction with AZU1 and MPO in their antibacterial role during NET formation. Regulation of Complement Activation PTX3 interaction with microorganisms is not...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion In conclusion, F. keratoplasticum and F. petroliphilum were the most frequent species in this study. Amphotericin B showed lower MICs against Fusarium species whereas the antifungal azoles and the fungicide difenoconazole exhibited higher MICs against FSSC. Ethics Statement Samples were collected during routine patient care and the study was retrospective, therefore it was determined by the local Institutional Review Board of the Hospital de Clínicas, Federal University of Paraná and CAPES that ethical clearance was not indicated. Author Contributions PH, AA-H, FQ-T, and JM designed the study....
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Abstract Pulmonary fungal infections, which can be opportunistic or endemic, lead to considerable morbidity and mortality. Such infections have multiple clinical presentations and imaging patterns, overlapping with those of various other diseases, complicating the diagnostic approach. Given the immensity of Brazil, knowledge of the epidemiological context of pulmonary fungal infections in the various regions of the country is paramount when considering their differential diagnoses. In addition, defining the patient immunological status will facilitate the identification of opportunistic infections, such as those occurring ...
Source: Radiologia Brasileira - Category: Radiology Source Type: research
ABSTRACT Candida spp. is associated with almost 80% of all nosocomial fungal infections and is considered a major cause of blood stream infections. In humans, Cryptococcosis is a disease of the lungs caused by the fungi Cryptococcus gattii and Cryptococcus neoformans. It can be potentially fatal, especially in immune-compromised patients. In a search for antifungal drugs, Deguelia duckeana extracts were assayed against these two fungi and also against Candida albicans, which causes candidiasis. Hexane branches and CH2Cl2 root extracts as well as the substances 4-hydroxylonchocarpine, 3,5,4 ′ -trimethoxy-4-prenylstilb...
Source: Revista Brasileira de Farmacognosia - Category: Drugs & Pharmacology Source Type: research
Conclusion: Patterns of invasive fungal infections are changing in many ways. In the midst of these evolving trends, IFI of the respiratory tractcontinue to remain important causes of morbidity and mortality. Diagnostic tools can be adequately used only if the treating physician is aware of the propensity of patients to acquire a fungal infection. Thus, continuous awareness and education is crucial for successful management of patients. Judicious use of antifungal medications as prophylactic measures must be employed, particularly in the critically ill and patients of HIV.
Source: Indian Journal of Medical Microbiology - Category: Microbiology Authors: Source Type: research
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