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antifungal drugs

Benjamin Leroy-Freschini, Giorgio Treglia, Xavier Argemi, Caroline Bund, Romain Kessler, Raoul Herbrecht, Alessio Imperiale
Background: Opportunistic invasive fungal infections (IFIs) comprise a heterogeneous spectrum of pathogens, whose early diagnosis remains challenging. Candida spp. and Aspergillus spp, the most frequent pathogens in immunocompromised patients, frequently affect lungs, liver, bone and skin. Aim: To evaluate the impact of 18F-FDG PET/CT in the management of immunocompromised patients with IFI. Design: A single-center retrospective study included 51 immunocompromised patients with IFI diagnosis undergoing 83 18F-FDG PET/CTs...
June 18, 2018: QJM: Monthly Journal of the Association of Physicians
Rabiye Altınbaş, Fatma Özakkaş, Ayşe Barış, Deniz Turan, Sümeyye Şen
Background/aim: Dermatophytes are the causative agents of dermatophytosis, which is a common disease worldwide that affects the hair, skin, and nails. Dermatophytes comprise more than 40 species in 3 genera: Microsporum, Trichophyton, and Epidermaphyton. In this study, we aimed to determine the effectiveness of seven antifungal agents: amphotericin B, terbinafine, itraconazole, voriconazole, ketoconazole, miconazole, and fluconazole. Materials and methods: A sensitivity study was performed using a microdilution method in accordance with the CLSI M38-A2 standards using isolates of Trichophyton rubrum (n = 55), Microsporum canis (n = 9), and Trichophyton interdigitale (n = 2), which were identified by sequencing the internal transcribed spacer region of the rDNA...
June 14, 2018: Turkish Journal of Medical Sciences
Wógenes N Oliveira, Lucas Amaral-Machado, Everton N Alencar, Henrique R Marcelino, Julieta Genre, Walicyranison P Silva-Rocha, Amanda D Gondim, Guilherme M Chaves, Matheus F Fernandes-Pedrosa, Eryvaldo Socrates T Egito
Amphotericin B (AmB), a potent antifungal drug, presents physicochemical characteristics that impair the development of suitable dosage forms. In order to overcome the AmB insolubility, several lipid carriers such as microemulsions have been developed. In this context, the bullfrog oil stands out as an eligible oily phase component, since its cholesterol composition may favor the AmB incorporation. Thus, the aim of this study was to develop a microemulsion based on bullfrog oil containing AmB. Moreover, its thermal stability, antifungal activity, and cytotoxicity in vitro were evaluated...
June 18, 2018: AAPS PharmSciTech
Miha Tome, Jure Zupan, Zorica Tomičić, Tadeja Matos, Peter Raspor
Candidemia and other forms of invasive fungal infections caused by Candida glabrata and to a lesser extent Saccharomyces cerevisiae are a serious health problem, especially if their steadily rising resistance to the limited range of antifungal drugs is taken into consideration. Various drug combinations are an attractive solution to the resistance problem, and some drug combinations are already common in the clinical environment due to the nature of diseases or therapies. We tested a few of the common antifungal-immunomodulatory drug combinations and evaluated their effect on selected strains of C...
2018: PeerJ
Pauline Dartevelle, Claire Ehlinger, Abdurraouf Zaet, Christian Boehler, Morgane Rabineau, Benoit Westermann, Jean-Marc Strub, Sarah Cianferani, Youssef Haïkel, Marie-Hélène Metz-Boutigue, Céline Marban
The excessive use of antifungal agents, compounded by the shortage of new drugs being introduced into the market, is causing the accumulation of multi-resistance phenotypes in many fungal strains. Consequently, new alternative molecules to conventional antifungal agents are urgently needed to prevent the emergence of fungal resistance. In this context, Cateslytin (Ctl), a natural peptide derived from the processing of Chromogranin A, has already been described as an effective antimicrobial agent against several pathogens including Candida albicans...
June 18, 2018: Scientific Reports
Sarah Allegra, Giovanna Fatiguso, Silvia De Francia, Elisa Pirro, Chiara Carcieri, Jessica Cusato, Amedeo De Nicolò, Valeria Avataneo, Giovanni Di Perri, Antonio D'Avolio
AIM: We explored the role of SNPs within the SLCO1B3, SLCO1B1, SLC22A6, ABCB1, ABCG2, SLCO3A1, CYP2C19, ABCC2, SLC22A1, ABCB11 and NR1I2 genes on voriconazole pharmacokinetics. PATIENTS & METHODS: 233 pediatric patients were enrolled. Drug plasma Ctrough was measured by a HPLC-MS method. Allelic discrimination was performed by qualitative real-time PCR. RESULTS: SLCO1B3 rs4149117 c.334 GT/TT (p = 0.046), ABCG2 rs13120400 c.1194 + 928 CC (p = 0...
June 19, 2018: Pharmacogenomics
Zohar Meir, Nir Osherov
The large increase in the population of immunosuppressed patients, coupled with the limited efficacy of existing antifungals and rising resistance toward them, have dramatically highlighted the need to develop novel drugs for the treatment of invasive fungal infections. An attractive possibility is the identification of possible drug targets within essential fungal metabolic pathways not shared with humans. Here, we review the vitamin biosynthetic pathways (vitamins A⁻E, K) as candidates for the development of antifungals...
June 17, 2018: Journal of Fungi (Basel, Switzerland)
Tariq Ismail, Nighat Fatima, Syed Aun Muhammad, Syed Saoud Zaidi, Nisar Rehman, Izhar Hussain, Najam Us Sahr Tariq, Imran Amirzada, Abdul Mannan
Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes...
2018: Acta Biochimica Polonica
Yuan Zhang, Vijai Kumar Reddy Tangadanchu, Rammohan R Yadav Bheemanaboina, Yu Cheng, Cheng-He Zhou
A series of carbazole-triazole conjugates were designed, synthesized and characterized by IR, NMR, and HRMS spectra. Biological assay showed that most of the synthesized compounds exhibited moderate and even strong antifungal activities, especially 3,6-dibromocarbazolyl triazole 5d displayed excellent inhibitory efficacy against most of the tested fungal strains (MIC = 2-32 μg/mL) and effectively fungicidal ability towards C. albicans, C. tropicals and C. parapsilosis ATCC 22019 (MFC = 4-8 μg/mL)...
June 15, 2018: European Journal of Medicinal Chemistry
Georgeta Serban, Oana Stanasel, Eugenia Serban, Sanda Bota
Pathogenic microorganisms are causative agents for different types of serious and even lethal infectious diseases. Despite advancements in medication, bacterial and fungal infections continue to be a growing problem in health care. As more and more bacteria become resistant to antibiotics used in therapy and an increasing number of invasive fungal species become resistant to current antifungal medications, there is considerable interest in the development of new compounds with antimicrobial activity. The compounds containing a heterocyclic ring play an important role among organic compounds with biological activity used as drugs in human and veterinary medicine or as insecticides and pesticides in agriculture...
2018: Drug Design, Development and Therapy
Kaelin M Bernier, Lynda A Morrison
Herpes simplex virus (HSV)-1 and HSV-2 cause painful blisters and shallow ulcers in exposed skin and mucosae during primary or recurrent infection. In addition, recurrent and potentially blinding HSV-1 infections of the eye afflict nearly half a million persons in the U.S. Current clinical therapies rely on nucleoside analog drugs such as acyclovir (ACV) or ganciclovir to ameliorate primary infections and reduce the frequency and duration of reactivations. However, these treatments do not fully suppress viral shedding and drug-resistant mutants develop in the eye and in vulnerable, immunosuppressed patients...
June 14, 2018: Antiviral Research
Laíse Diana Dos Santos Brandão, Douglas Boniek, Maria Aparecida de Resende Stoianoff, Flávia Maria Rezende da Mata, Paulo Roberto Medeiros de Azevedo, José Veríssimo Fernandes, Vânia Sousa Andrade
Vulvovaginal candidiasis (VVC) is an inflammatory disease of the vulva and vagina caused by different yeasts of the genus Candida which is responsible for infection in pregnant patients who attended Maternidade Escola Januário Cicco, Rio Grande do Norte, Brazil. From 41 samples, 19 yeasts were identified phenotypically as Candida albicans, and one as C. glabrata which is reported as the non-albicans species most frequently isolated from vulvovaginitis. The susceptibility to selected antifungal agents (fluocytosine, fluconazole, voriconazole, amphotericin B, caspofungin and micafungin) was determined, and the association between patient related signs and symptoms aided the construction of an epidemiological profile...
June 16, 2018: Letters in Applied Microbiology
Adane Bitew, Yeshiwork Abebaw
BACKGROUND: Vulvovaginal candidiasis is a global issue of concern due to its association with economic costs, sexually transmitted infections, and ascending genital tract infection. The aim of this study was to determine species distribution and antifungal susceptibility pattern of Candida species causing vulvovaginal candidiasis. METHODS: A cross sectional study was conducted from November 2015 to December 2016 at the Family Guidance Association of Ethiopia. Vaginal swabs collected from study subjects that were clinically diagnosed with vulvovaginal candidiasis were cultured...
June 15, 2018: BMC Women's Health
Christopher L Hager, Emily L Larkin, Lisa A Long, Mahmoud A Ghannoum
Background: Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration. Objectives: Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis. Methods: Mice were immunosuppressed 3 days prior to infection and 1 day post-infection...
April 19, 2018: Journal of Antimicrobial Chemotherapy
Anthony Nash, Thomas Sewell, Rhys A Farrer, Alireza Abdolrasouli, Jennifer M G Shelton, Matthew C Fisher, Johanna Rhodes
Summary: The increase of antifungal drug resistance is a major global human health concern and threatens agriculture and food security; in order to tackle these concerns, it is important to understand the mechanisms that cause antifungal resistance. The curated Mycology Antifungal Resistance Database (MARDy) is a web-service of antifungal drug resistance mechanisms, including amino acid substitutions, tandem repeat sequences and genome ploidy. MARDy is implemented on a Linux, Apache, MySQL and PHP web development platform and includes a local installation of BLASTn of the database of curated genes...
April 20, 2018: Bioinformatics
Nilce M Martinez-Rossi, Tamires A Bitencourt, Nalu T A Peres, Elza A S Lang, Eriston V Gomes, Natalia R Quaresemin, Maíra P Martins, Lucia Lopes, Antonio Rossi
Dermatophytes comprise pathogenic fungi that have a high affinity for the keratinized structures present in nails, skin, and hair, causing superficial infections known as dermatophytosis. A reasonable number of antifungal drugs currently exist on the pharmaceutical market to control mycoses; however, their cellular targets are restricted, and fungi may exhibit tolerance or resistance to these agents. For example, the stress caused by antifungal and cytotoxic drugs in sub-inhibitory concentrations promotes compensatory stress responses, with the over-expression of genes involved in cellular detoxification, drug efflux, and signaling pathways being among the various mechanisms that may contribute to drug tolerance...
2018: Frontiers in Microbiology
Martin Schmidt, Dominic Tran-Nguyen, Patrick Chizek
Boron presents at physiological pH in the form of boric acid (BA), a molecule that has both positive and negative effects on biological processes. In medicine, BA is used as a topical treatment for vaginal yeast infections by Candida species because of its well-documented but poorly understood effect on inhibition of growth in general and of invasive, hyphal growth in particular. The present study examines the influence of BA on carbohydrate energy metabolism of this common human pathogen. Starting from previous findings about an inhibition of key NAD-dependent enzymes by BA in vitro, we confirmed that such an inhibition occurs in permeabilized C...
September 2018: Journal of Trace Elements in Medicine and Biology
Laura Friggeri, Tatiana Y Hargrove, Zdzislaw Wawrzak, Anna L Blobaum, Girish Rachakonda, Craig W Lindsley, Fernando Villalta, W David Nes, Maurizio Botta, F Peter Guengerich, Galina I Lepesheva
Due to the increase in the number of immunocompromised patients, the incidence of invasive fungal infections is growing but the treatment efficiency remains unacceptably low. The most potent clinical systemic antifungals (azoles) are the derivatives of two scaffolds: ketoconazole and fluconazole. Being the safest antifungal drugs, they still have shortcomings, mainly because of pharmacokinetics and resistance. Here we report the successful use of the target fungal enzyme, sterol 14α-demethylase (CYP51), for structure-based design of novel antifungal drug candidates by minor modifications of VNI [(R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)], an inhibitor of protozoan CYP51 that cures Chagas disease...
June 12, 2018: Journal of Medicinal Chemistry
Daiana Macedo, Florencia Leonardelli, Catiana Dudiuk, Laura Theill, Matías S Cabeza, Soledad Gamarra, Guillermo Garcia-Effron
Rhizopus oryzae is the most prevalent causative agent of Mucormycosis, an increasingly reported opportunistic fungal infection. These mucormycetes are intrinsically resistant to Candida - and Aspergillus -active antifungal azole drugs such as fluconazole and voriconazole, respectively. Despite of its importance, the molecular mechanisms of its intrinsic azole resistance have not been elucidated yet. The aim of this work is to establish if the Rhizopus oryzae CYP51 genes are the unique responsible for voriconazole and fluconazole intrinsic resistance in these fungal pathogens...
June 11, 2018: Antimicrobial Agents and Chemotherapy
Saskia du Pré, Nicola Beckmann, Mariana Cruz Almeida, Graham E M Sibley, Derek Law, Alexandra C Brand, Mike Birch, Nick D Read, Jason D Oliver
F901318 (olorofim) is a novel antifungal drug that is highly active against Aspergillus species. Belonging to a new class of antifungals called the orotomides, F901318 targets dihydroorotate dehydrogenase (DHODH) in the de novo pyrimidine biosynthesis pathway. In this study, the antifungal effects of F901318 against Aspergillus fumigatus were investigated. Live-cell imaging revealed that, at a concentration of 0.1 μg/ml, F901318 completely inhibited germination, but conidia continued to expand by isotropic growth for >120 h...
June 11, 2018: Antimicrobial Agents and Chemotherapy
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