Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.

The present study investigated the association of the non-steroidal anti-inflammatory drug ibuprofen with itraconazole, fluconazole and amphotericin B against Cryptococcus neoformans isolates. The minimal inhibitory concentration (MIC) was found according to M27-A3 protocol and in vitro interactions were evaluated using checkerboard microdilution method. Synergism was demonstrated between azoles and ibuprofen for most isolates. However, no synergistic effects were seen when amphotericin B was combined with ibuprofen. Therefore, our results suggest that ibuprofen presents clinical potential when combined with azole drugs in the treatment of cryptococcosis.

Abstract Fusarium spp. has been associated with a broad spectrum of emerging infections collectively termed fusariosis. This review includes articles published between 2005 and 2018 that describe the characteristics, clinical management, incidence, and emergence of these fungal infections. Fusarium solani and F. oxysporum are globally distributed and represent the most common complexes. Few therapeutic options exist due to intrinsic resistance, especially for the treatment of invasive fusariosis. Therefore, the use of drug combinations could be an important alternative for systemic antifungal resistance. Increase in the number of case reports on invasive fusariosis between 2005 and 2018 is evidence of the emergence of this fungal infection.

ABSTRACT Griseofulvin (GF) and terbinafine (TF) are commonly used drugs to treat dermatophytosis, a fungal infection of the skin. Today there is an increase in drug resistance to these antifungals which highlight the need for alternative synergistic therapies. Minimum Inhibitory Concentration (MIC) of GF and TF were determined against fungi clinical isolates from local hospitals with values ranging 0.03-2.0 µg mL-1 and 0.24-4.0 µg mL-1, respectively. A checkboard test was used to determine the combination of GF:TF which could induce an additive effect against the fungi isolates Multidrug-resistant isolates showed susceptibility after treatment with 16:2 µg mL-1 GF:TF. An MTT assay further verified that GF and TF combinations have greater additive effect against pathological and multidrug-resistant isolates than antifungals alone. Herein we disclose GF:TF combinations that could constitute as a possible new anti-dermatophyte therapy.

Abstract Triazole fungicides are used broadly for the control of infectious diseases of both humans and plants. The surge in resistance to triazoles among pathogenic populations is an emergent issue both in agriculture and medicine. The non-rational use of fungicides with site-specific modes of action, such as the triazoles, may increase the risk of antifungal resistance development. In the medical field, the surge of resistant fungal isolates has been related to the intensive and recurrent therapeutic use of a limited number of triazoles for the treatment and prophylaxis of many mycoses. Similarities in the mode of action of triazole fungicides used in these two fields may lead to cross-resistance, thus expanding the spectrum of resistance to multiple fungicides and contributing to the perpetuation of resistant strains in the environment. The emergence of fungicide-resistant isolates of human pathogens has been related to the exposure to fungicides used in agroecosystems. Examples include species of cosmopolitan occurrence, such as Fusarium and Aspergillus, which cause diseases in both plants and humans. This review summarizes the information about the most important triazole fungicides that are largely used in human clinical therapy and agriculture. We aim to discuss the issues related to fungicide resistance and the recommended strategies for preventing the emergence of triazole-resistant fungal populations capable of spreading across environments.

In the last times, focus on plant research has increased all over the world. Euphorbia tirucalli L., a plant known popularly as Aveloz, and originally used in Africa, has been drawing attention for its use in the United States and Latin America, both for use as an ornamental plant and as a medicinal plant. E. tirucalli L. is a member of the family Euphorbiaceae and contains many diterpenoids and triterpenoids, in particular phorbol esters, apparently the main constituent of this plant, which are assumed to be responsible for their activities in vivo and in vitro. The in vitro antifungal activities of Euphorbia tirucalli (L.) against opportunistic yeasts were studied using microbroth dilution assay. The results showed that aqueous extract and latex preparation were effective against ten clinical strains of Cryptococcus neoformans in vitro (Latex and extract MIC range of 3.2 - > 411 µg/mL). Aiming the safe use in humans, the genotoxic effects of E. tirucalli were evaluated in human leukocytes cells. Our data show that both aqueous extract and latex preparation have no genotoxic effect in human leukocytes cells in vitro. Although the results cannot be extrapolated by itself for use in vivo, they suggest a good perspective for a therapeutic application in future. In conclusion, our results show that the aqueous extract and latex preparation from E. tirucalli L. are antifungal agents effectives against several strains of C. neoformans and do not provoke DNA damage in human leukocyte cells, considering the concentrations tested.

INTRODUÇÃO: Nos últimos anos, o oportunismo das candidíases vem se tornando cada vez mais recorrente e de difícil tratamento, principalmente em virtude da emergência de novas espécies, bem como devido à diminuição à suscetibilidade aos antifúngicos. O sucesso do tratamento das infecções causadas por Candida depende cada vez mais do conhecimento da espécie e do seu perfil de sensibilidade. OBJETIVOS: Esse estudo teve por objetivo realizar uma investigação do perfil de suscetibilidade de amostras de candidíase oral e vulvovaginal, de pacientes residentes no oeste de Santa Catarina, aos antifúngicos anfotericina B, fluconazol e miconazol. MATERIAL E MÉTODOS: A suscetibilidade de 60 cepas de Candida spp. foi avaliada frente aos antifúngicos. As determinações das concentrações inibitórias mínimas e concentrações fungicidas mínimas foram realizadas com base no documento M27-A2 do Clinical and Laboratory Standards Institute (CLSI). RESULTADOS: No presente estudo foi observado alto índice de resistência para o fluconazol e para a anfotericina B. O miconazol foi o antifúngico que demonstrou melhor eficácia sobre as cepas testadas. DISCUSSÃO: As amostras dessa região do estado de Santa Catarina demonstram baixa suscetibilidade aos antifúngicos, o que explica a alta taxa de recidivas nas infecções, mas alerta para a emergência de cepas com resistência adquirida. CONCLUSÃO: A prévia avaliação por testes de suscetibilidade in vitro deve nortear a conduta de um tratamento antifúngico efetivo para os casos de candidíase de repetição, principalmente em locais de alta prevalência desta infecção oportunista, como no oeste de Santa Catarina.

INTRODUCTION: In recent years, the opportunism of yeast infections is becoming more recurrent and difficult to treat, mainly due to the emergence of new species as well as due to decreased susceptibility to antifungal agents. The successful treatment of infections caused by Candida is increasingly dependent on knowledge of the causative species and its susceptibility profile to antifungals. OBJECTIVES: This study aimed to conduct an investigation of the susceptibility profile of samples of oral and vulvovaginal candidiasis in patients of western Santa Catarina to the antifungal amphotericin B, fluconazole and miconazole. MATERIAL AND METHODS: The susceptibility of 60 strains of Candida spp. was evaluated for antifungal agents. The determination of minimum inhibitory concentrations and minimal fungicidal concentrations were based on document M27-A2 of the CLSI. RESULTS: In this study, we observed a high rate of resistance to fluconazole and amphotericin B. The miconazole was the antifungal agent significantly more effective on the strains tested. DISCUSSION: The samples in this region of the state of Santa Catarina showed a low susceptibility to antifungal agents, which explains the high rate of relapses in infections, but alert to the emergence of strains with acquired resistance. CONCLUSION: The preliminary assessment by in vitro susceptibility testing should guide the conduct of effective therapy for cases of recurrent mainly in areas of high prevalence of opportunistic infection, as in western of Santa Catarina.

The aim of this study was to assess the use of pesticides on farms located in the Lambedor River watershed in Guatambu, State of Santa Catarina, as well as to determine, by micronucleus testing, the risk of genotoxic impact. Samples from locally collected Cyprinus carpio, Hypostomus punctatus, Rhamdia quelen and Oreochromis niloticus gave evidence of a mean increase in micronuclei frequency from 6.21 to 13.78 in 1,000 erythrocytes, a clear indication of the genotoxic potenciality of pesticide residues in regional dams, and their significant contribution to local environmental contamination.