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https://www.readbyqxmd.com/read/27897041/novel-antifungal-agents-a-patent-review-2013-present
#1
María Victoria Castelli, Marcos Gabriel Derita, Silvia Noelí López
Superficial infections involving the skin and mucosa are the most common fungal disease in humans. Fungi can also produce invasive infections (IFI), which are increasing in incidence among the growing population of immunocompromised patients, and are characterized by a high mortality rate. Amphotericin B, new triazoles and echinocandins have improved treatment options in IFI. However, the frequency of less common and more resistant fungi, the limited activity of available antifungal drugs and their undesirable side effects reflect the urgent need for the development of new therapeutic strategies...
November 29, 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/27895625/evaluation-of-virulence-factors-in-vitro-resistance-to-osmotic-stress-and-antifungal-susceptibility-of-candida-tropicalis-isolated-from-the-coastal-environment-of-northeast-brazil
#2
Diana L Zuza-Alves, Sayama S T Q de Medeiros, Luanda B F C de Souza, Walicyranison P Silva-Rocha, Elaine C Francisco, Maria C B de Araújo, Reginaldo G Lima-Neto, Rejane P Neves, Analy S de Azevedo Melo, Guilherme M Chaves
Several studies have been developed regarding human health risks associated with the recreational use of beaches contaminated with domestic sewage. These wastes contain various micro-organisms, including Candida tropicalis. In this context, the objective of this study was to characterize C. tropicalis isolates from the sandy beach of Ponta Negra, Natal, Rio Grande do Norte, Brazil, regarding the expression of in vitro virulence factors, adaptation to osmotic stress and susceptibility to antifungal drugs. We analyzed 62 environmental isolates and observed a great variation among them for the various virulence factors evaluated...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27886119/synthesis-and-antifungal-screening-of-2-1-5-alkyl-arylalkylpyrazin-2-yl-ethylidene-hydrazono-1-3-thiazolidin-4-ones
#3
Veronika Opletalova, Jan Dolezel, Jiri Kunes, Vladimir Buchta, Marcela Vejsova, Marta Kucerova-Chlupacova
Two novel thiosemicarbazones and eight novel 2-{[1-(5-alkyl/arylalkylpyrazin-2-yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones were prepared and tested against a panel of eight fungal strains-Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton interdigitale 445. 1,3-Thiazolidin-4-ones exhibited activity against all strains, the most potent derivative was 2-{[1-(5-butylpyrazin-2-yl)ethylidene]hydrazono}e-1,3-thiazolidin-4-one...
November 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27872079/the-paradoxical-effect-of-echinocandins-in-aspergillus-fumigatus-relies-on-recovery-of-the-%C3%AE-1-3-glucan-synthase-fks1
#4
Veronika Loiko, Johannes Wagener
Echinocandins target the fungal cell wall by inhibiting biosynthesis of the cell wall carbohydrate β-1,3-glucan. This antifungal drug class exhibits a paradoxical effect which is characterized by the resume of growth of otherwise susceptible strains at higher drug concentrations (approx.4-32 μg/ml). The nature of this phenomenon is still unknown. In this study, we analyzed the paradoxical effect of the echinocandin caspofungin on the pathogenic mold Aspergillus fumigatus Using a conditional fks1 mutant, we show that very high caspofungin concentrations exert an additional antifungal activity beside inhibition of the β-1,3-glucan synthase...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872072/pharmacokinetics-of-anidulafungin-in-critically-ill-patients-in-the-intensive-care-unit-with-suspected-or-proven-invasive-fungal-infections
#5
R J M Brüggemann, V Middel-Baars, D W de Lange, A Colbers, A R J Girbes, P Pickkers, E L Swart
Echinocandins, such as anidulafungin are first line treatment for candidemia or invasive candidiasis in critically ill patients. There is conflicting data on the pharmacokinetic properties of anidulafungin in ICU patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included. Patient were considered evaluable when a pharmacokinetic curve on day 3 could be completed. 23 out of 36 patients (7 female, 16 male) were evaluable. Median (range) age and bodyweight were 66 (28-88) yr and 76 (50-115) kg...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872063/in-vitro-exposure-to-increasing-micafungin-concentrations-easily-promotes-echinocandin-resistance-in-candida-glabrata-isolates
#6
María Ángeles Bordallo-Cardona, Pilar Escribano, Elia Gómez G de la Pedrosa, Laura Judith Marcos-Zambrano, Rafael Cantón, Emilio Bouza, Jesús Guinea
We assessed the in vitro susceptibility of five echinocandin-susceptible C. glabrata isolates after exposure to micafungin. The direct exposure to plates at different micafungin concentrations resulted in the inhibition of growth at 0.062 μg/ml. The progressive exposure was performed on plates with 0.031 μg/ml of micafungin and sequentially propagated on plates containing the next two-fold concentration; the MICs of micafungin and anidulafungin increased sequentially and all the isolates became echinocandin-resistant showing fks2 mutations...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27859978/breakthrough-fungemia-due-to-candida-fermentati-with-fks1p-mutation-under-micafungin-treatment-in-a-cord-blood-transplant-recipient
#7
Takaaki Konuma, Shunsuke Takahashi, Tomohiko Kiyuna, Yuta Miharu, Masato Suzuki, Hiroko Shibata, Seiko Kato, Satoshi Takahashi, Arinobu Tojo
The prophylactic use of antifungal drugs in allogeneic hematopoietic cell transplant recipients has revealed that the rate of non-albicans candidemia has increased. We herein report the case of a patient with adult T-cell leukemia who developed candidemia due to Candida fermentati during micafungin treatment after cord blood transplantation. The isolate was identified on day 47 by sequencing of the internal transcribed spacer region of the ribosomal RNA gene. The sequencing of the hot spot region of fks1p of isolate revealed naturally occurring amino acid substitutions, which conferred reduced echinocandin susceptibility...
November 15, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/27859907/identification-and-functional-ascertainment-of-the-pneumocystis-jirovecii-potential-drug-targets-gsc1-and-kre6-involved-in-glucan-synthesis
#8
Amanda Luraschi, Ousmane H Cissé, Marco Pagni, Philippe M Hauser
The most efficient drug against the human pathogenic fungus Pneumocystis jirovecii is cotrimoxazole targeting the folate biosynthesis. However, resistance towards it is emerging and adverse effects occur in some patients. Studies in rodent models suggested that echinocandins could be useful to treat Pneumocystis pneumonia. Echinocandins inhibit the catalytic subunit Gsc1 of the enzymatic complex ensuring the synthesis of 1,3-β glucan, an essential constituent of cell walls of most fungi. Besides, inhibitors of the enzyme Kre6 involved in the synthesis of 1,6-β glucan, another essential component of fungal walls, were recently described...
November 17, 2016: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/27858242/epidemiology-and-reporting-of-candidaemia-in-belgium-a-multi-centre-study
#9
C Trouvé, S Blot, M-P Hayette, S Jonckheere, S Patteet, H Rodriguez-Villalobos, F Symoens, E Van Wijngaerden, K Lagrou
The primary aim of this study was to collect national epidemiological data on candidaemia and to determine the reporting time of species identification and antifungal susceptibility in clinical practice. During a 1-year period (March 2013 until February 2014), every first Candida isolate from each episode of candidaemia was included prospectively from 30 Belgian hospitals. Identification and susceptibility testing were performed according to local procedures and isolates were sent to the National Reference Center for Mycosis...
November 17, 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27855078/echinocandin-resistance-in-candida-spp-isolated-from-liver-transplant-recipients
#10
Gwénolé Prigent, Nawel Aït-Ammar, Eric Levesque, Arnaud Fekkar, Jean-Marc Costa, Sarra El Anbassi, Françoise Foulet, Christophe Duvoux, Jean-Claude Merle, Eric Dannaoui, Françoise Botterel
Liver transplant recipients are at risk of invasive fungal infections, especially candidiasis. Echinocandin is recommended as prophylactic treatment but is increasingly associated with resistance. Our aim was to assess echinocandin drug resistance in Candida spp. isolated from liver transplant recipients treated with this antifungal class. For this, all liver-transplanted patients in a University Hospital (Créteil, France) between January and June of 2013 and 2015 were included. Susceptibilities of Candida isolates to echinocandins were tested by Etest® and EUCAST reference method...
November 14, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27842800/anti-candida-albicans-natural-products-sources-of-new-antifungal-drugs-a-review
#11
REVIEW
A Zida, S Bamba, A Yacouba, R Ouedraogo-Traore, R T Guiguemdé
INTRODUCTION: Candida albicans is the most prevalent fungal pathogen in humans. Due to the development of drug resistance, there is today a need for new antifungal agents for the efficient management of C. albicans infections. Therefore, we reviewed antifungal activity, mechanisms of action, possible synergism with antifungal drugs of all natural substances experimented to be efficient against C. albicans for future. METHODS: An extensive and systematic review of the literature was undertaken and all relevant abstracts and full-text articles analyzed and included in the review...
November 11, 2016: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/27837518/molecular-detection-of-resistance-to-echinocandins
#12
Brunella Posteraro, Antonietta Vella, Elena De Carolis, Maurizio Sanguinetti
In the last years, life-threatening fungal diseases have increased significantly, due to the rising number of human individuals susceptible to fungal infections, which are in part complicated by the emergence of antifungal drug-resistant pathogens. Among yeasts, Candida albicans and Candida glabrata are the most common organisms responsible for invasive fungal diseases. The molecular detection of echinocandin resistance in Candida species may represent a useful means of monitoring the incidence of clinical isolates with antifungal resistance-associated gene alterations...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27837500/systemic-antifungal-agents-current-status-and-projected-future-developments
#13
Seyedmojtaba Seyedmousavi, Haleh Rafati, Macit Ilkit, Ali Tolooe, Mohammad T Hedayati, Paul Verweij
By definition, an antifungal agent is a drug that selectively destroys fungal pathogens with minimal side effects to the host. Despite an increase in the prevalence of fungal infections particularly in immunocompromised patients, only a few classes of antifungal drugs are available for therapy, and they exhibit limited efficacy in the treatment of life-threatening infections. These drugs include polyenes, azoles, echinocandins, and nucleoside analogs. This chapter focuses on the currently available classes and representatives of systemic antifungal drugs in clinical use...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27837497/the-changing-epidemiology-of-invasive-fungal-infections
#14
David A Enoch, Huina Yang, Sani H Aliyu, Christianne Micallef
Invasive fungal infections (IFI) are an emerging problem worldwide with invasive candidiasis and candidemia responsible for the majority of cases. This is predominantly driven by the widespread adoption of aggressive immunosuppressive therapy among certain patient populations (e.g., chemotherapy, transplants) and the increasing use of invasive devices such as central venous catheters (CVCs). The use of new immune modifying drugs has also opened up an entirely new spectrum of patients at risk of IFIs. While the epidemiology of candida infections has changed in the last decade, with a gradual shift from C...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27821250/antifungal-pharmacodynamics-latin-america-s-perspective
#15
Javier M Gonzalez, Carlos A Rodriguez, Maria Agudelo, Andres F Zuluaga, Omar Vesga
The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field...
November 5, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27821139/micafungin-versus-caspofungin-in-the-treatment-of-candida-glabrata-infection-a-case-report
#16
Shoko Merrit Yamada, Yusuke Tomita, Tomotsugu Yamaguchi, Toshiaki Matsuki
BACKGROUND: Micafungin and caspofungin, which are both echinocandins, elicit their antifungal effects by suppressing the synthesis of β-D-glucan, an essential component of fungal cell walls. If micafungin is not effective against a fungal infection, is it unreasonable to switch to caspofungin? CASE PRESENTATION: An 80-year-old Asian man presented to our hospital with brain and lung abscesses. Klebsiella pneumonia and Escherichia coli were identified by sputa culture and Streptococcus mitis was identified in the brain abscess culture obtained by drainage surgery...
November 8, 2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27820668/new-facets-of-antifungal-therapy
#17
Ya-Lin Chang, Shang-Jie Yu, Joseph Heitman, Melanie Wellington, Ying-Lien Chen
Invasive fungal infections remain a major cause of morbidity and mortality in immunocompromised patients, and such infections are a substantial burden to healthcare systems around the world. However, the clinically available armamentarium for invasive fungal diseases is limited to 3 main classes (i.e., polyenes, triazoles, and echinocandins), and each has defined limitations related to spectrum of activity, development of resistance, and toxicity. Further, current antifungal therapies are hampered by limited clinical efficacy, high rates of toxicity, and significant variability in pharmacokinetic properties...
November 7, 2016: Virulence
https://www.readbyqxmd.com/read/27799221/frequency-of-the-paradoxical-effect-measured-using-eucast-with-micafungin-anidulafungin-and-caspofungin-against-candida-spp-isolates-causing-candidemia
#18
Laura Judith Marcos-Zambrano, Pilar Escribano, Carlos Sánchez-Carrillo, Emilio Bouza, Jesús Guinea
We report data on the frequency of the paradoxical effect of echinocandins against Candida spp. (n= 602 incident isolates) using the EUCAST EDef 7.2 procedure. The paradoxical effect for one or more echinocandins was observed in 16% of the isolates. However, differences between species were found, and the paradoxical effect was more common in Candida tropicalis (P<0.001). Caspofungin was the drug in which the paradoxical effect was most common, followed by anidulafungin and micafungin (P<0.001).
October 31, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27799206/a-multi-center-study-of-method-dependent-epidemiological-cutoff-values-ecvs-for-resistance-detection-in-candida-spp-and-aspergillus-spp-to-amphotericin-b-and-echinocandins-for-the-etest-agar-diffusion-method
#19
A Espinel-Ingroff, M Arendrup, E Cantón, S Cordoba, E Dannaoui, J García-Rodríguez, G M Gonzalez, N P Govender, E Martin-Mazuelos, C Lass-Flörl, M Lackner, M J Linares Sicilia, M A Rodriguez-Iglesias, T Pelaez, R K Shields, G Garcia-Effron, J Guinea, M Sanguinetti, J Turnidge
Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C...
October 31, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27798213/monotherapy-or-combination-therapy-of-isavuconazole-and-micafungin-for-treating-murine-mucormycosis
#20
Teclegiorgis Gebremariam, Nathan P Wiederhold, Abdullah Alqarihi, Priya Uppuluri, Nkechi Azie, John E Edwards, Ashraf S Ibrahim
OBJECTIVES: Previously we demonstrated the benefit of isavuconazole in treating murine mucormycosis due to Rhizopus. We wanted to determine the efficacy of isavuconazole in treating murine mucormycosis caused by Mucor, the second most common cause of the disease. Furthermore, because we previously determined that Rhizopus possesses the target enzyme for echinocandins and micafungin has activity against murine mucormycosis, we compared the activity of combination therapy (isavuconazole + micafungin) with placebo, either drug alone or standard therapy of liposomal amphotericin B (LAmB) in treating pulmonary murine mucormycosis caused by Rhizopus delemar...
October 24, 2016: Journal of Antimicrobial Chemotherapy
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