Reversal of itraconazole resistance in Sporothrix brasiliensis and Sporothrix schenckii by nonsteroidal anti-inflammatory drugs / Reversión de la resistencia a itraconazol en Sporothrix brasiliensis y Sporothrix schenckii con antiinflamatorios no esteroideos

Background: The emergence of resistant isolates has brought challenges to the treatment of sporotrichosis, prompting the search for new therapeutic strategies. Previous studies reported that nonsteroidal anti-inflammatory drugs (NSAIDs) show in vitro activity against several pathogenic fungi, including species of Candida, Cryptococcus, and Trichosporon.AimsThis study aimed to investigate the in vitro efficacy of three NSAIDs (acetylsalicylic acid, diclofenac sodium, and ibuprofen), alone and in combination with itraconazole, against eleven clinical isolates of Sporothrix brasiliensis and Sporothrix schenckii.MethodsMinimal inhibitory concentrations were determined by the broth microdilution method. Drug interactions and the fractional inhibitory concentration index of NSAIDs and itraconazole were assessed by the checkerboard method.ResultsWhen used alone, ibuprofen was the most active NSAID, followed by acetylsalicylic acid. Combinations of NSAIDs with itraconazole showed synergistic antifungal activity against nine isolates. It was also found that itraconazole combined with acetylsalicylic acid, diclofenac sodium, or ibuprofen, led to resistance reversal in two, three, and five of the six drug-resistant isolates, respectively. (AU)

Antecedentes: La aparición de cepas resistentes a los antifúngicos convencionales ha supuesto un nuevo desafío en el tratamiento de la esporotricosis y ha impulsado la búsqueda de nuevas estrategias terapéuticas. Estudios anteriores han descrito que los antiinflamatorios no esteroideos (AINE) tienen actividad in vitro contra diversos hongos patógenos, incluidas especies de Candida, Cryptococcus y Trichosporon.ObjetivosEste estudio tuvo como objetivo investigar la eficacia in vitro de tres AINE (ácido acetilsalicílico, diclofenaco sódico e ibuprofeno), aisladamente y en combinación con itraconazol, contra once aislamientos clínicos de Sporothrix brasiliensis y Sporothrix schenckii.MétodosLas concentraciones inhibitorias mínimas fueron determinadas según el método de microdilución en caldo. Las interacciones farmacológicas y el índice de concentración inhibitoria fraccional de los AINE y de itraconazol fueran evaluadas mediante el método del tablero de ajedrez.ResultadosComo molécula única, el ibuprofeno fue el AINE más activo, seguido del ácido acetilsalicílico. Las combinaciones de los AINE con itraconazol exhibieron actividades antifúngicas sinérgicas frente a nueve aislamientos. También se observó que la combinación de itraconazol con ácido acetilsalicílico, diclofenaco sódico o ibuprofeno provocó la reversión de la resistencia en dos, tres y cinco de los seis aislamientos resistentes a los fármacos, respectivamente. (AU)

Chlorhexidine Nanoemulsion: A New Antiseptic Formulation.

INTRODUCTION: Nanoparticle solutions have been studied to improve antimicrobial effect. The aim of this study was to develop, characterize, and evaluate the in vitro and in vivo antiseptic efficacy of 0.25% aqueous-based chlorhexidine nanoemulsion (NM-Cl 0.25% w/v). METHODS: The NM-Cl 0.25% w/v (2.5mg/mL) and free chlorhexidine nanoemulsion (FCN; same composition of NM-Cl without the molecule of chlorhexidine) were synthetized by the spontaneous emulsification method. Characterization analyses of physical and chemical properties were performed. The NM-Cl 0.25% w/v was compared with chlorhexidine 0.5% alcohol base (CS-Cl 0.5%) in vitro studies (microdilution study and kill curve study), and in vivo study (antisepsis of rats dorsum). Kruskal-Wallis test was used between groups and inside the same group, at different sample times and the Mann-Whitney test was performed when difference was detected. RESULTS: The NM-Cl 0.25% w/v presented adequate physicochemical characteristics for a nanoemulsion, revealing a more basic pH than FCN and difference between zeta potential of NM-Cl 0.25% w/v and FCN. The NM-Cl 0.25% w/v and CS-Cl 0.5% solutions were more effective on Gram-positive than on Gram-negative bacteria (p≤0.05). NM-Cl 0.25% w/v presented upper antiseptic effect in the microdilution study and residual antiseptic effect was maintained for a longer time when compared to CS-Cl 0.5% (kill curve study). The four-fold (minimal inhibitory concentration) of NM-Cl 0.25% were the formulations with most durable effect within those tested, presenting residual effect until T6 for both bacteria. In the in vivo study, both formulations (NM-Cl 0.25% w/v and CS-Cl 0.5%) had a reduction of the microorganisms in the skin of the rats (p<0.0001) not revealing any difference between the formulations at different times, showing the antiseptic effect of NM-Cl (p≤0.05). CONCLUSION: Both in vitro and in vivo experiments demonstrated that NM-Cl showed promising future as an antiseptic for cutaneous microbiota.

Antifungal susceptibilities and identification of species of the Sporothrix schenckii complex isolated in Brazil.

Sporotrichosis is a subacute or chronic mycosis caused worldwide by the dimorphic species complex, Sporothrix schenckii. We studied 85 isolates recovered in Brazil to verify their identification and evaluate their in vitro antifungal susceptibility patterns. Based on phenotypic tests (microscopic features, ability to grow at 30°C and 37°C, colony diameters, as well as assimilation of sucrose and raffinose) and molecular assays (amplification of a fragment of the calmodulin gene), the strains were identified as S. schenckii, S. brasiliensis and S. globosa, with a predominance of S. schenckii isolates. There was 37.7% disagreement between the phenotypic and genotypic identification methodologies. In general, terbinafine was the most active drug, followed by ketoconazole and itraconazole, and the less active fluconazole and voriconazole. Five isolates (one S. globosa and four S. schenckii) were found to be itraconazole-resistant strains but, in general, there were no differences in the in vitro antifungal susceptibility profiles among the Sporothrix species.

Frequency of onychomycoses in chronic renal failure patients undergoing hemodialysis in Porto Alegre, Brazil.

Onychomycosis is one of the most frequent infections affecting the fingernails or the toenails and it is caused mainly by dermatophytes. The aim of the study was to assess the frequency of onychomycoses in hemodialysis patients and to relate sex, age, duration of hemodialysis and causes of renal failure to the development of nail disorders. The study included 100 patients with chronic renal failure undergoing hemodialysis. The patients underwent detailed clinical examination of the toenails and those with any kind of clinical finding had nail scraping for mycological testing. In the study population, the frequency of onychomycosis was 39%. The most commonly isolated fungi were dermatophytes (69.23%), Candida spp. (15.38%) and nondermatophyte molds (15.38%). T. interdigitale was the most prevalent fungus followed by Candida ssp. and T. rubrum. The risk of onychomycosis increases by 1.9% for each additional year in age and diabetic patients are 88% more likely to develop onychomycosis than nondiabetic ones. The duration of hemodialysis treatment and sex were not associated with the development of onychomycosis. In conclusion, in hemodialysis patients, the frequency of onychomycosis was higher in those at advanced age and with diabetes.

Actividad antimicrobiana del cloruro de 2-metacriloil oxietil trimetilamonio contra Candida sp / Antimicrobial activity of [2-(methacryloyloxy)ethyl]trimethylammonium chloride against Candida spp

Antecedentes. La estomatitis protética es la forma más común de infección bucal producida por especies de Candida, siendo Candida albicans el agente etiológico más común. Diversos autores han intentado asociar agentes antifúngicos o antisépticos a los materiales de revestimiento blando o a las resinas acrílicas de las prótesis dentales, pero sin éxito. Por ello, se ha investigado un compuesto de amonio cuaternario (2-metacriloil oxietil trimetilamonio [MADQUAT]), que copolimeriza con los metacrilatos y que podría actuar como inhibidor de levaduras. Objetivos. El objetivo de este estudio fue evaluar la actividad in vitro del MADQUAT contra especies de Candida. Métodos. Se utilizaron 31 cepas de Candida para determinar la actividad antifúngica in vitro. Se determinó la concentración mínima inhibitoria (CMI) y la concentración mínima fungicida del MADQUAT, así como de la nistatina. Resultados. El MADQUAT presentó propiedades antifúngicas en las concentraciones entre 6,25 y > 100mg/ml y actividad fungicida entre 25 y > 100mg/ml. Los estudios cuantitativos de la actividad fungistática y fungicida del MADQUAT demostraron actividad fungistática contra todas las cepas de Candida albicans, Candida krusei y Candida parapsilosis, revelando actividad fungicida contra algunas cepas de otras especies. Conclusiones. El MADQUAT presenta actividad antifúngica contra Candida spp. Además, la sensibilidad a dicho compuesto es distinta entre las diferentes especies considerando los valores de la CMI y la actividad fungicida o fungistática(AU)

Background. Candida-associated denture stomatitis is the most common manifestation of oral candidal infection, caused mainly by Candida albicans. Several authors have attempted to add antifungal agents or antiseptics to denture temporary soft lining materials or to denture acrylic resins, without relevant results. Therefore, the investigation of a quaternary ammonium functionalized compound [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MADQUAT), which copolymerizes with methacrylates and which could act as a fungal inhibitor, is of paramount importance. Aims. To evaluate the in vitro activity of MADQUAT against Candida species. Methods. Thirty-one Candida strains were used to determine the in vitro antifungal activity of this compound. The minimum inhibitory concentrations and minimum fungicidal concentrations of MADQUAT and nystatin were determined. Results. MADQUAT showed antifungal properties at concentrations of 6.25 to > 100mg/ml, and fungicidal activity between 25 and > 100mg/ml. The quantitative determinations of the fungistatic and fungicidal activity of MADQUAT showed fungistatic activity against all Candida albicans, Candida krusei and Candida parapsilosis strains, revealing fungicidal activity against some strains of the other species. Conclusions. MADQUAT has antifungal activity against Candida spp. Moreover, the sensitivity to this substance varies across the different species in terms of MIC values and fungicidal or fungistatic activity(AU)