Alterations in growth and branching of Neurospora crassa caused by sub-inhibitory concentrations of antifungal agents / Alteraciones de crecimiento y ramificación en Neurospora crassa provocadas por concentraciones subinhibitorias de agentes antimicóticos

Six antifungal agents at subinhibitory concentrations were used for investigating their ability to affect the growth and branching in Neurospora crassa. Among the antifungals herein used, the azole agent ketoconazole at 0.5 μg/ml inhibited radial growth more than fluconazole at 5.0 μg/ml while amphotericin B at 0.05 μg/ml was more effective than nystatin at 0.05 μg/ml. Morphological alterations in hyphae were observed in the presence of griseofulvin, ketoconazole and terbinafine at the established concentrations. The antifungal agents were more effective on vegetative growth than on conidial germination. Terbinafine markedly reduced growth unit length (GU) by 54.89%, and caused mycelia to become hyperbranched. In all cases, there was a high correlation between hyphal length and number of tips (r > 0.9). All our results showed highly significant differences by ANOVA, (p < 0.001, α = 0.05). Considering that the hyphal tip is the main interface between the fungus and its environment /through which enzymes and toxins are secreted and nutrients absorbed, it would not be desirable to obtain a hyperbranched mycelia with inefficient doses of antifungal drugs.

Se investigó el efecto de seis agentes antimicóticos en concentraciones subinhibitorias sobre el crecimiento y la ramificación en Neurospora crassa. El agente azólico ketoconazol a la concentración de 0,5 μg/ml inhibió el crecimiento radial más que el fluconazol a 5,0 μg/ml, y la anfotericina B a 0,05 μg/ ml fue más eficiente que 0,05 μg/ml de nistatina, entre los agentes poliénicos usados. En presencia de griseofulvina, ketoconazol y terbinafina a las concentraciones establecidas se observaron alteraciones morfológicas en las hifas. Los agentes antimicóticos fueron más eficientes sobre el crecimiento vegetativo que sobre la germinación conidial. La terbinafina redujo marcadamente (54,89%) la longitud de la unidad de crecimiento y provocó la hiperramificación del micelio. En todos los casos, existió gran correlación entre la longitud y el número de ápices de las hifas (r > 0,9). Todos los resultados mostraron diferencias altamente significativas de acuerdo con ANOVA (p < 0,001, α = 0,05). Considerando que el ápice de la hifa es la principal interfase entre el hongo y su ambiente, a través de la cual las enzimas y las toxinas son secretadas y los nutrientes son absorbidos, un micelio hiperramificado resultante de dosis ineficientes de agentes antimicóticos sería perjudicial.

[ effects of antifungal azoles on inflammatory cytokine production in human keratinocytes]

Azoles drugs are being used successfully in treatment of fungal infections. Recently, immunosuppressive effects of some of these agents have been reported. Keratinocytes as the major cells of the skin, have an important role in innate immunity against pathogenic agents. Considering the scanty of information about the effects of azoles on immune responces, this study was conducted to assess the expression and secretion of inflammatory cytokines in keratinocytes following treatment with azole drugs. This is an exprimental study conducted in molecular biology division in Tehran University of Medical Sciences and Immunodermatology Department in Vienna Medical University. Primery keratinocytes were cultured and treated with different concentrations of fluconazole, itraconazole, ketoconazole and griseofulvin. Secreted IL1, IL6 and TNF-alpha by keratinocytes in culture supernatant were measured by quantitative enzyme immunoassay technique. Moreover, expression of the genes encoding IL1 and IL8 was evaluated by Real Time-PCR. Treatment of keratinocytes with different concentrations of fluconazole and low concentration of ketoconazole resulted in decrease in IL1 secretion, but itraconazole and griseofulvin did not show such an effect at the same concentrations. In addition, none of the examined drugs had an effect on secretion level of IL6 and TNF-alpha. Quantitative analysis of IL1 and IL8 encoding genes revealed that transcription on these genes might be suppressed following treatment with fluconazole or ketoconazole. Fluconazole and ketoconazole might modulate the expression and secretion of IL1 and IL8 and affect the direction of immune responses induced by keratinocytes

Antimicóticos en niños / Antifungals in Children

Las micosis superficiales son padecimientos frecuentes en la infancia y para su manejo se pueden utilizar antimicóticos tanto tópicos como sistémicos. Sin embargo, en las últimas décadas, ha aumentado la población infantil susceptible a infecciones diseminadas o sistémicas por agentes oportunistas que ponen en riesgo la vida. Las principales son la candidosis y la aspergilosis. Se han desarrollado nuevos antimicóticos con espectros más amplios de acción y menor toxicidad, pero la mayoría de los reportes en la literatura se refieren a estudios hechos en adultos, cuyos resultados son extrapolados a la población pediátrica. La presente revisión tiene como objetivo condensar la información referente al uso de antimicóticos en niños, con énfasis en las diferencias farmacocinéticas con respecto a los adultos y las indicaciones principales para su uso (AU)

Superficial mycoses are common in childhood, either topical or systemic antifungals can be used for treatment. However, in the past decade, the pediatric population at risk of a disseminated or systemic infection by opportunistic fungi has increased. The most important are candidiasis and aspergillosis. New antifungals, with a wider spectrum of action and less toxicity have been developed, nevertheless, most of the studies and reports of the literature focus on adults and the findings are extrapolated to children. The objective of this paper is to review what has been published on the use of antifungals in the pediatric age, focusing in pharmacokinetic differences regarding adults and current indications for this group of drugs (AU)

Production of a growth dependent metabolite active against dermatophytes by Streptomyces rochei AK 39.

BACKGROUND & OBJECTIVE: Dermatophytes responsible for causing dermatophytoses in humans have acquired resistance to certain antimycotic drugs. We isolated naturally occurring actinomycetes with an ability to produce metabolites having antimycotic property. The timecourse of antifungal metabolite production in terms of arbitrary units (AU) under optimum conditions was studied. METHODS: Water and soil samples were collected from various locations. The actinomycetes were isolated on starch casein medium and screened for their antifungal activity against yeasts and molds including dermatophytes. One promising isolate which showed a unique, stable and interesting property of inhibiting only dermatophytes was selected and characterized. Optimization of antifungal metabolite production in terms of AU using Trichphyton rubrum as target was done. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of the culture supernatant from the isolate and that of griseofulvin were determined for all dermatophytes. RESULTS: Of the 218 actinomycete isolates, 14 per cent produced the metabolites having antifungal activity. The selected actinomycete, identified as Streptomyces rochei AK 39 produced metabolite, which was active against only dermatophytes whereas yeasts and other molds were resistant to it. Starch casein medium was found to be good for inducing antifungal activity in the isolate. The maximum antifungal metabolite production (400 AU/ml) was achieved in the late log phase, which remained constant during the stationery phase, and it was extracellular in nature. The MIC and MFC values of the culture supernatant from the isolate against the dermatophytes were within the range 1.25 to 5 and 1.25 to 10 AU/ml respectively. INTERPRETATION & CONCLUSION: The metabolite from Streptomyces rochei AK 39 was produced during late log phase and was active against only dermatophytes with a greater potency than griseofulvin. However, this needs further investigation using purified powdered form of the active component.

A study of dermatophytes and their in-vitro antifungal sensitivity.

Of the 150 clinically suspected cases of Dermatophytosis studied, majority of the cases were from age group 11-20 and 21-30 (51.4%), Tinea corporis (48.7%) and Tinea capitis (18%) were the commonest clinical types. The isolation rate was 24% (36) of which 19 (52.7%) were Trichophyton rubrum, 11 (30.55%) were Trichophyton mentagrophytes and 4 (11.1%) were Trichophyton violaceum. One isolate each of Microsporum gypseum & Epidermophyton floccosum were obtained. Griseofulvin proved to be the best drug with a sensitivity of 94.4% followed by Miconazole (75% sensitive). Tolnaftate showed a sensitivity of 47.22%. For Clotrimazole only 30.55% of the isolates were sensitive.

Invitro drug sensitivity of Trichophyton species against griseofulvin and ketoconazole.

The in vitro activity of griseofulvin and ketoconazole was investigated against Trichophyton mentagrophytes (Robin) Blanchard and T. Simii (Pinoy) Stockdale, Mackenzie and Austwick. A gradual decrease in growth was observed with increase in concentration of both antibiotics. Ketoconazole was the more effective antibiotic than griseofulvin as it observed to inhibit > 50% mycelial weight even at a lower concentration of 100 ppm. While griseofulvin was effective to cause > 50% growth inhibition only at higher dosage of 400 ppm.

Tiña de la cabeza. Tratamiento actual en cinco pacientes / Tinea capitis. Current treatment in five patients

Se discuten las opciones terapéuticas en cinco pacientes con tiña de la cabeza. Se concluye que los antimicóticos de los que se dispone en el mercado: griseofulvina, itraconazol y terbinafina, son efectivos y presentan pocos efectos adversos. La griseofulvina sigue siendo utilizada por su eficacia y bajo costo

Disk diffusion susceptibility testing of dermatophytes with imidazoles.

In vitro susceptibility testing of 43 isolates of dermatophytes was carried out against imidazoles-ketoconazole, miconazole and econazole and griseofulvin by agar dilution and disk diffusion methods. Econazole was the most effective drug inhibiting all the isolates at a concentration of 0.1 microgram ml-1. The MIC 50s and MIC 90s for ketoconazole and miconazole were 1 and 2.5 mg ml-1 whereas the values for griseofulvin were 1 and 5 micrograms ml-1. Good correlation was seen between the MIC and sizes of zones of inhibition around the disks. Regression analysis was used to measure the degree of correlation between the MIC values and matched averaged zones of inhibition and the correlation coefficients for econazole, ketoconazole, miconazole and griseofulvin were -0.5554, -0.5886, -0.8558 and -0.8268 (p < 0.001) respectively.

Atividade de alguns antimicóticos contra fungos isolados de diferentes classes de pacientes / Some antifungals acrivity against isolated fungi from immunocompromised hosts

Pacientes imunocomprometidos säo considerados de alto risco para aquisiçöes fúngicas graves, disseminadas a partir de processos localizados. Os antifúngicos têm sido administrados de modo empírico e, em vários casos têm sido mostrado ineficazes e altamente tóxicos para o hospedeiro. Entre outros fatores, esses problemas médicos säo agravados pela carência de uma rotineira execuçäo de antibiograma para fungos a fim de subsidiar a clínica na escolha do antimicótico adequado a cada caso. Tais testes tornam-se cada vez mais necessários, em vista da crescente comprovaçäo da falta de resposta aos antifúngicos poliêmicos, azóicos e da griseofulvina contra fungos isolados da regiäo podal de indivíduos considerados sadios e de pacientes imunocomprometidos. A determinaçäo da concentraçäo inibitória mínima (CIM) foi realizada por meio da técnica de diluiçäo em ágar YNB modificado, e a da concentraçäo fungicida mínima (CFM) foi realizada em ASD. Os antifúngicos mostraram-se principalmente inibidores, e raras vezes letais, frente aos fungos isolados. De modo geral, o cetoconazol foi o antifúngico mais ativo e o fluconazol o menos ativo. Os dermatófitos, oriundos de pacientes transplantados foram menos sensíveis a determinadas concentraçöes das drogas. Com base neste trabalho, pode-se ressaltar a importância da execuçäo rotineira de antibiograma para fungos, notadamente para os isolados a partir de imunocomprometidos

In-vitro susceptibility of dermatophytes to griseofulvin and ketoconazole and bioassay of ketoconazole

Antibiogram together with minimum inhibitory concentration [MIC] of griseofulvin and ketoconazole were determined against 24 dermatophyte strains that were isolated from different ring worm lesions by using the agar dilution methods. These dermatophytes included 7 strains of Trichophyton violaceum, 6 strains of Microsporon canis, 5 strains of Trichophyton rubrum, 3 strains of Trichophyton mentagrophytes, 2 strains of Trichophyton schoenlinii and one strain of Epidermophyton floccosum. All tested dermatophytes were generally susceptible to ketoconazole and to griseofulvin in varying concentrations except one strain of Trichophyton mentagrophytes which was resistant to all concentration of griseofulvin. The [MIC] of griseofulvin Indicated a high susceptibility [0.78 micro gram/ml] of Microsporum canis and a low susceptibility [12.5 micro gram/ml] of Epidermophyton floccosum, The [MIC] of ketoconazole Indicated a high susceptibility of Trichophyton rubrum and Trichophyton violaceum [2 micro gram/ml and 4 micro gram/ml for each respectively] and low susceptibility [16 micro gram/ml] to Epidermpophyton floccosum. Bioassay of ketoconazole on the tested serum samples, indicated that its level had ranged between 0.7 and 4 micro gram/ml and proved that the drug was not accumulated

Os caminhos da investigaçäo de novos antifúngicos / The pathways of the investigation of new antifungal drugs

Neste artigo, säo tecidas consideraçöes sobre a necessidade de se pesquisar novas drogas antifúngicas mais efetivas contra o agente agressor e menos tóxicas para o ser humano, bem como drogas para uso profilático. Säo revistos os pontos vulneráveis dos fungos e os mecanismos de açäo dos principais antifúngicos, tanto de uso tópico quanto de administraçäo oral, existentes no mercado. Finalmente, o autor apresenta os caminhos possíveis de investigaçäo deste tipo de quimioterápico, visando atender as necessidades atuais

Cetoconazol e griseofulfina: quando esta, quando aquele? / Ketoconazole and griseofulvin: when this, when that?

Após revisäo das propriedades farmacodinâmicas e fungistáticas do cetoconazol e griseofulvina, de estudos comparativos entre a eficácia de um e de outro medicamento no tratamento das dermatofitoses, concluiu-se ser a griseofulvina a droga de primeira escolha na terapêutica sistêmica dessa micose sugerindo o cetoconazol como excelente opçäo nos casos de efeitos adversos ou contra-indicaçöes da griseofulvina

Effect of some antibiotics on Macrophomina phaseolina, a charcoal rot fungus of soybean.

Effect of agrimycin-100, ampicillin, griseofulvin and tetracycline on colony growth of Macrophomina phaseolina, incitant of charcoal rot of soybean has been studied in vitro. Amongst them tetracycline posed most effective inhibiting the growth by 73.9% at 1000 micrograms/ml concentration. On the basis of effectiveness antibiotics have been listed as tetracycline greater than ampicillin greater than griseofulvin greater than agrimycin-100.

Evaluation of in vitro antifungal activity of ketoconazole and griseofulvin

Antifungal activity of Ketoconazole and Griseofulvin was evaluated on 36 isolates of different strains of dermatophytes and yeasts, and the results were compared. Ketoconazole had a broad spectrum of antifungal activity although not all the strains were sensitive to it, yet it was much superior in its activity to Griseofuvin