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Equinocandinas Echinocandins  [cached]
Jorge A Cortés L,July A Russi N
Revista chilena de infectología , 2011,
Abstract: Las equinocandinas -caspofugina, micafungina y ani-dulafungina- son lipopéptidos que inhiben el crecimiento fúngico al unirse a la β-(1,3) d glucano sintetasa, enzima esencial para la síntesis en la pared celular de hongos como Candida spp, y menos importante en el caso de especies de Aspergillus y Fusarium. Se revisa la historia, farmacología y los diferentes ensayos clínicos que han evidenciado similar eficacia clínica a la de anfotericina B para el manejo de infecciones micóticas como candidemia, candidiasis invasora y aspergilosis, inclusive en casos refractarios al manejo inicial. Estos medicamentos tienen menor toxicidad y en pocos casos hay necesidad de retiro del tratamiento. Dado su espectro y tolerabilidad similar, su farmacología permite diferenciarlas. Se dispone de información limitada de estudios clínicos que las comparen entre ellas, limitando la extrapolación de la información a todo el grupo. Sin embargo, presentan eficacia clínica comprobada en pacientes con varias micosis invasoras. The echinocandins, caspofugin, micafungin, and anidulafungin, are lipopeptides that inhibit fungal growth by binding to β - (1.3) d glucan synthase. This enzyme is responsible for the formation of the peptidoglycan cell wall, and it is essential in fungi such as Candida spp, but less important in the case of Aspergillus and Fusarium species. We review the history, pharmacology and clinical trials that have showed clinical efficacy similar to amphotericin B for the management of fungal infections such as candidemia, invasive candidiasis and aspergillosis, even in cases refractory to initial treatment. These drugs have less toxicity and discontinuation is uncommonly required. Despite similar spectrum and tolerability, there are several pharmacological differences. Only a few clinical trials compare the clinical efficacy between them and their clinical application cannot be generalized. However, the echinocandins have demonstrated clinical efficacy in patients with invasive candidiasis and in others forms of systemic mycoses.
Pharmacotherapy of Candida Infections with Echinocandins
Ana Espinel-Ingroff,Emilia Canton,Estrella Martin-Mazuelos,Javier Pemán
Clinical Medicine : Therapeutics , 2009,
Abstract: The classic recommended antifungal agents for the treatment of invasive Candida infections were amphotericin B, a lipid formulation of amphotericin B and fluconazole in both neutropenic or nonneutropenic patients as either primary or alternative therapies. Voriconazole has been recommended when additional coverage for filamentous fungi is needed (e.g. neutropenic patients). More recently and based on well designed comparative clinical trials, the three echinocandins, caspofungin, anidulafungin and micafungin have been added as primary or alternative therapies especially for critically ill or neutropenic patients. In general, the echinocandins are most useful when patients have previously been exposed to an azole or are unstable.
ANTIMYCOTIC ACTIVITY OF SIX MEDICINAL PLANTS  [PDF]
VISHAL NARAYAN SHINDE
Indian Streams Research Journal , 2013,
Abstract: The variable extracts of six medicinal plants prepared in 80% methanol and distilled water and were tested for their antimycotic activity against five different phytopathogenic fungi such as Alternaria carthami, Alternaria humicola, Fusarium oxysporum, Fusarium roseum, Pullularia pullulans. Among all the plant extracts, methanol extract of Lawsonia inermis and Hyptis sauvolens leaves were showed significant antifungal activity against targeted phytopathogens. Methanol extracts displayed maximum antifungal activity as compared to aqueous extracts. The antifungal activity revealed by these plants could be attributed to the synergetic effect of two or more chemical constituent.
Stimulation of Chitin Synthesis Rescues Candida albicans from Echinocandins  [PDF]
Louise A. Walker equal contributor,Carol A. Munro equal contributor,Irene de Bruijn,Megan D. Lenardon,Alastair McKinnon,Neil A. R. Gow
PLOS Pathogens , 2008, DOI: 10.1371/journal.ppat.1000040
Abstract: Echinocandins are a new generation of novel antifungal agent that inhibit cell wall β(1,3)-glucan synthesis and are normally cidal for the human pathogen Candida albicans. Treatment of C. albicans with low levels of echinocandins stimulated chitin synthase (CHS) gene expression, increased Chs activity, elevated chitin content and reduced efficacy of these drugs. Elevation of chitin synthesis was mediated via the PKC, HOG, and Ca2+-calcineurin signalling pathways. Stimulation of Chs2p and Chs8p by activators of these pathways enabled cells to survive otherwise lethal concentrations of echinocandins, even in the absence of Chs3p and the normally essential Chs1p, which synthesize the chitinous septal ring and primary septum of the fungus. Under such conditions, a novel proximally offset septum was synthesized that restored the capacity for cell division, sustained the viability of the cell, and abrogated morphological and growth defects associated with echinocandin treatment and the chs mutations. These findings anticipate potential resistance mechanisms to echinocandins. However, echinocandins and chitin synthase inhibitors synergized strongly, highlighting the potential for combination therapies with greatly enhanced cidal activity.
Echinocandins: A ray of hope in antifungal drug therapy  [cached]
Grover Neeta
Indian Journal of Pharmacology , 2010,
Abstract: Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3)-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall. Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT) and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis. The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.
Antimycotic and Antifungal Activities of Amaranth and Buckwheat Extracts  [PDF]
Silvia Mosovska,Lucia Birosova
Asian Journal of Plant Sciences , 2012,
Abstract: Nowadays, there has been an increased interest in various natural plants as a source of biological active compounds including polyphenols. Important sources of these phytochemicals are less known pseudocereals such as amaranth and buckwheat. The objective of this study was determination of antimycotic and antifungal effects of mentioned pseudocereals. Antimicrobial screening against selected three yeast strains and four strains of fungi was carried out on DMSO buckwheat and amaranth extracts prepared by alkali hydrolyses. Results suggested variation in the antimicrobial properties of tested extracts. The studied extracts suppressed growth of Aspergillus flavus, Fusarium culmorum and Alternaria alternata. No inhibitory effect was observed against Rhizopus oryzae and tested yeast.
Allergic Contact Dermatitis from Diethyl Sebacate in a Topical Antimycotic Medicament  [PDF]
Ayaka Hirao, Naoki Oiso, Megumi Hama, Noriko Higashimori, Yoichi Tatsumi, Akira Kawada
Journal of Cosmetics, Dermatological Sciences and Applications (JCDSA) , 2012, DOI: 10.4236/jcdsa.2012.23040
Abstract: Diethyl sebacate is used in topical medicaments in United States and Japan. We described a case of allergic contact dermatitis from diethyl sebacate in a topical antimycotic medicament. Allergic reaction to diethyl sebacate is likely more common because our group has found three of eight sensitized cases. We believe that an investigation regarding the sensitized frequency to diethyl sebacate would conduct to improve the safety of products in United States and Japan.
Nuevos antifúngicos: Las equinocandinas New antifungal agents: Echinocandins  [cached]
Alexis Diomedi P.
Revista chilena de infectología , 2004,
Abstract: La familia de lipopéptidos conocidos como equinocandinas emerge como las nuevas "penicilinas antifúngicas", capaces de destruir la pared celular micótica al inhibir la síntesis del glucano, fundamental constituyente de la estructura fúngica. Las equinocandinas han mostrado in vitro e in vivo, ser fungicidas contra la mayoría de las especies de Candida y fungistáticas contra Aspergillus sp, sin exhibir acción sobre células de mamíferos. Tres agentes emergen como los principales representantes de esta clase; caspofungina, micafungina y anidulafungina, estando las dos primeras ya licenciadas para su uso en humanos. Su óptimo perfil de seguridad, con baja incidencia y severidad de efectos adversos, cómoda posología y pocas interacciones con otros fármacos, representan notables ventajas para la terapéutica antifúngica moderna. Comparativamente han mostrado tener eficacia clínica similar a anfotericina B, sin la toxicidad que este polieno tradicionalmente muestra, lo que sumado a la ausencia de antagonismo con otros antifúngicos permite sugerir que la terapia combinada pudiera ser un nuevo estándar de manejo para la tan temida aspergilosis invasora The lipopeptide family known as echinocandins emerge as the new "antifungal penicillins", because their ability to destroy the fungal cell wall as they inhibit glucan synthesis, the main component of fungal structure. Echinocandins are fungicidal in vitro and in vivo against most Candida species and fungistatic against Aspergillus sp, without antifungal activity over mammal cells. Three drugs are representative of this class; caspofungin, micafungin and anidulafungin, the two first have been licensed for human use. Their optimal security profile, with low incidence and severity of adverse effects, kind posology and few interactions with other drugs, represent noticeable advantages for modern antifungal therapy. They have similar clinical efficacy as amphotericin B, without its toxicity, which besides the absence of antagonism with other antifungal drugs, allows to suggest that combined antifungal therapy could represent a new standard for the management of the feared invasive aspergillosis
Microcolony Imaging of Aspergillus fumigatus Treated with Echinocandins Reveals Both Fungistatic and Fungicidal Activities  [PDF]
Colin J. Ingham, Peter M. Schneeberger
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035478
Abstract: Background The echinocandins are lipopeptides that can be employed as antifungal drugs that inhibit the synthesis of 1,3-β-glucans within the fungal cell wall. Anidulafungin and caspofungin are echinocandins used in the treatment of Candida infections and have activity against other fungi including Aspergillus fumigatus. The echinocandins are generally considered fungistatic against Aspergillus species. Methods Culture of A. fumigatus from conidia to microcolonies on a support of porous aluminium oxide (PAO), combined with fluorescence microscopy and scanning electron microscopy, was used to investigate the effects of anidulafungin and caspofungin. The PAO was an effective matrix for conidial germination and microcolony growth. Additionally, PAO supports could be moved between agar plates containing different concentrations of echinocandins to change dosage and to investigate the recovery of fungal microcolonies from these drugs. Culture on PAO combined with microscopy and image analysis permits quantitative studies on microcolony growth with the flexibility of adding or removing antifungal agents, dyes, fixatives or osmotic stresses during growth with minimal disturbance of fungal microcolonies. Significance Anidulafungin and caspofungin reduced but did not halt growth at the microcony level; additionally both drugs killed individual cells, particularly at concentrations around the MIC. Intact but not lysed cells showed rapid recovery when the drugs were removed. The classification of these drugs as either fungistatic or fungicidal is simplistic. Microcolony analysis on PAO appears to be a valuable tool to investigate the action of antifungal agents.
Efficacy and potency of lichens of Mizoram as antimycotic agents  [cached]
AMRITESH C. SHUKLA*, M. CHINLAMPIANGA, ARCHANA VERMA, ANUPAM DIKSHIT and D.K. UPRETI
Indian Phytopathology , 2012,
Abstract: Antifungal property of aqueous and acetone extracts of two lichens was investigated against plant pathogenic fungi viz., Alternaria alternata, Aspergillus flavus and Penicillium italicum shows strong efficacy against the test fungi. Acetone extracts of both the lichen spp. were more effective than aqueous extracts. Aqueous and acetone extracts of Stereocaulon sp. were more effective than Ramalina sp. The aqueous and acetone extracts of Ramalina sp. and Stereocaulon sp. at 50 μl/ml concentration contains broad fungi toxic spectrum. Based on these findings as well as after detailed in vitro investigations, the active constituents of lichens can be synthesized and used as a potential substitute of synthetic fungicides.
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