Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model.

IMPORTANCE: Multidrug resistance is a rising problem among non-Candida albicans species, such as Candida auris. This therapeutic problem has been very important during the COVID-19 pandemic. The World Health Organization has included C. auris in its global priority list of health-threatening fungi, to study this emerging multidrug-resistant species and to develop effective alternative therapies. In the present study, the synergistic effect of the combination of amphotericin B and echinocandins has been demonstrated against blood isolates of C. auris. Different susceptibility responses were also observed between aggregative and non-aggregative phenotypes. The antifungal activity of these drug combinations against C. auris was also demonstrated in the Caenorhabditis elegans host model of candidiasis, confirming the suitability and usefulness of this model in the search for solutions to antimicrobial resistance.

[Clinical usefulness of triazole derivatives in the management of fungal infections]. / La utilidad clínica de los derivados triazólicos en el tratamiento de las infecciones fúngicas.

Current therapy for mycoses is limited to the use of a relative reduced number of antifungal drugs. Although amphotericin B still remains considered as the "gold standard" for treatment, acute and chronic toxicity, such as impairment of renal function, limits its use and enhances the investigation and clinical use other chemical families of antifungal drugs. One of these chemical class of active drugs are azole derivatives, discovered in 70s and introduced in clinical practice in 80s. Being the most prolific antifungal class, investigation about more molecules, with a safer and better pharmacological profile, active against a wide spectrum of fungi, with a wide range of administration routes gives us some azole representatives.

Sertaconazole: an antifungal agent for the topical treatment of superficial candidiasis.

Sertaconazole is a useful antifungal agent against mycoses of the skin and mucosa, such as cutaneous, genital and oral candidiasis and tinea pedis. Its antifungal activity is due to inhibition of the ergosterol biosynthesis and disruption of the cell wall. At higher concentrations, sertaconazole is able to bind to nonsterol lipids of the fungal cell wall, increasing the permeability and the subsequent death of fungal cells. Fungistatic and fungicidal activities on Candida are dose-dependent. The antifungal spectrum of sertaconazole includes deramophytes, Candida, Cryptococcus, Malassezia and also Aspergillus, Scedosporium and Scopulariopsis. Sertaconazole also shows an antimicrobial activity against streptococci, staphylococci and protozoa (Trichomonas). In clinical trials including patients with vulvovaginal candidiasis, a single dose of sertaconazole produced a higher cure rate compared with other topical azoles such as econazole and clotrimazole, in shorter periods. Sertaconazole has shown an anti-inflammatory effect that is very useful for the relief of unpleasant symptoms.

In vitro activities of natural products against oral Candida isolates from denture wearers.

BACKGROUND: Candida-associated denture stomatitis is a frequent infectious disease. Treatment of this oral condition is difficult because failures and recurrences are common. The aim of this study was to test the in vitro antifungal activity of pure constituents of essentials oils. METHODS: Eight terpenic derivatives (carvacrol, farnesol, geraniol, linalool, menthol, menthone, terpinen-4-ol, and α-terpineol), a phenylpropanoid (eugenol), a phenethyl alcohol (tyrosol) and fluconazole were evaluated against 38 Candida isolated from denture-wearers and 10 collection Candida strains by the CLSI M27-A3 broth microdilution method. RESULTS: Almost all the tested compounds showed antifungal activity with MIC ranges of 0.03-0.25% for eugenol and linalool, 0.03-0.12% for geraniol, 0.06-0.5% for menthol, α-terpineol and terpinen-4-ol, 0.03-0.5% for carvacrol, and 0.06-4% for menthone. These compounds, with the exception of farnesol, menthone and tyrosol, showed important in vitro activities against the fluconazole-resistant and susceptible-dose dependent Candida isolates. CONCLUSIONS: Carvacrol, eugenol, geraniol, linalool and terpinen-4-ol were very active in vitro against oral Candida isolates. Their fungistatic and fungicidal activities might convert them into promising alternatives for the topic treatment of oral candidiasis and denture stomatitis.

[In vitro antifungal activity of micafungin]. / Actividad antifúngica in vitro de la micafungina.

BACKGROUND: Micafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses with a wide antifungal spectrum for the most common pathogenic fungi. Micafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3- D-glucan synthesis, an essential molecule for the cell wall architecture, with different con sequences for Candida and Aspergillus, being micafungin fungicide for the former and fungistatic for the latter. AIM: To describe the in vitro antifungal spectrum of micafungin based in the scientific and medical lite rature of recent years. METHODS: We have done a bibliographic retrieval using the scientific terms, "micafungin", "activity", "Candida", "Aspergillus", "fungi", "mycos*", "susceptibility", in PubMed/Medline from the National Library of Medicine de EE.UU. from 2005 to 2009. RESULTS: We can underline that most than 99% of Candida isolates are susceptible to < or = 2microg/ml of micafungin. MIC are very low (< or = 0.125microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2microg/ml. The activity of micafungin is excellent against those medical important species of Aspergillus. However, its activity is very low against Cryptococcus and the Zygomycetes. CONCLUSIONS: The excellent activity of micafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.

[Activity of micafungin against Candida biofilms]. / Actividad de la micafungina contra las biopelículas de Candida.

BACKGROUND: Most recalcitrant infections are associated to colonization and microbial biofilm development. These biofilms are difficult to eliminate by the immune response mechanisms and the current antimicrobial therapy. AIM: To describe the antifungal of micafungin against fungal biofilms based in the scientific and medical literature of recent years. METHODS: We have done a bibliographic retrieval using the scientific terms "micafungin", "activity", "biofilm", "Candida", "Aspergillus", "fungi", "mycos"*, susceptibility, in PubMed/Medline from the National Library of Medicine from 2006 to 2009. RESULTS: Most current antifungal agents (amphotericin B and fluconazole) and the new azole antifungals have no activity against fungal biofilms. However, micafungin and the rest of echinocandins are very active against Candida albicans, Candida dubliniensis, Candida glabrata, and Candida krusei biofilms but their activities are variable and less strong against Candida tropicalis and Candida parapsilosis biofilms. Moreover, they have not activities against the biofilms of Cryptococcus y Trichosporon. CONCLUSIONS: The activity of micafungin against Candida biofilms gives more strength to its therapeutic indication for candidaemia and invasive candidiasis associated to catheter, prosthesis and other biomedical devices.

Actividad antifúngica in vitro de la micafungina / In vitro antifungal activity of micafungin

Antecedentes: La micafungina es una aportación farmacológica nueva y eficaz para el tratamiento de las micosis invasoras con un espectro antifúngico que engloba a los hongos patógenos más comunes, y especialmente a los géneros Candida y Aspergillus. Su mecanismo de acción se basa en la inhibición de la síntesis de β-1,3-D-glucano, molécula esencial para la pared fúngica. Este mecanismo tiene como consecuencia 2 tipos de acciones: una acción fungicida contra Candida y una acción fungistática contra Aspergillus y otros hongos filamentosos. Objetivo: Describir el espectro antifúngico in vitro de micafungina, tomando como base los datos publicados en los últimos años. Métodos: Se ha realizado una búsqueda bibliográfica mediante el empleo de los términos “micafungin”, “activity”, “Candida”, “Aspergillus”, “fungi”, “mycos*”, “susceptibility”, en la base de datos PubMed/Medline de la National Library of Medicine desde enero de 2006 hasta enero de 2009. Resultados: Destaca que más del 99% de los aislamientos de Candida son sensibles a concentraciones menores o iguales de 2 μg/ml de micafungina. Dentro de esta sensibilidad in vitro a la micafungina, las concentraciones mínimas inhibitorias observadas son más bajas para Candida albicans, Candida glabrata, Candida tropicalis y Candida krusei, mientras que son más elevadas para Candida parapsilosis y Candida guilliermondii. La actividad fue excelente frente a la mayoría de las especies de Aspergillus de interés médico. Sin embargo, su actividad es prácticamente nula contra Cryptococcus y los zigomicetos. Conclusiones: Esta excelente actividad antifúngica hace que la micafungina sea una indicación terapéutica de primera línea para el tratamiento de las candidemias y candidiasis invasoras en pacientes sin neutropenia (AU)

Background: Micafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses with a wide antifungal spectrum for the most common pathogenic fungi. Micafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the β-1,3- D-glucan synthesis, an essential molecule for the cell wall architecture, with different consequences for Candida and Aspergillus, being micafungin fungicide for the former and fungistatic for the latter. Aim: To describe the in vitro antifungal spectrum of micafungin based in the scientific and medical literature of recent years. Methods: We have done a bibliographic retrieval using the scientific terms, “micafungin”, “activity”, “Candida”, “Aspergillus”, “fungi”, “mycos*”, “susceptibility”, in PubMed/Medline from the National Library of Medicine de EE.UU. from 2005 to 2009. Results: We can underline that most than 99% of Candida isolates are susceptible to ≤ 2 μg/ml of micafungin. MIC are very low (≤ 0.125 μg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations ≤ 2 μg/ml. The activity of micafungin is excellent against those medical important species of Aspergillus. However, its activity is very low against Cryptococcus and the Zygomycetes. Conclusions: The excellent activity of micafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients (AU)

Actividad de la micafungina contra las biopelículas de Candida / Activity of micafungin against Candida biofilms

Antecedentes: Muchas de las micosis más recalcitrantes al tratamiento se asocian a la colonización y la formación de biopelículas que son difíciles de eliminar por parte de los mecanismos defensivos inmunológicos y con el tratamiento antimicrobiano habitual. Objetivo: Describir la utilidad de la micafungina en las biopelículas fúngicas a partir de los datos publicados en los últimos años. Métodos: Se ha realizado una búsqueda bibliográfica mediante el empleo de los términos “micafungin”, “activity”, “biofilm”, “Candida”, “Aspergillus”, “fungi”, “mycos*”, “susceptibility”, en la base de datos PubMed/Medline de la National Library of Medicine de Estados Unidos desde enero de 2006 hasta enero de 2009. Resultados: La mayoría de los antifúngicos convencionales (anfotericina B y fluconazol) y los nuevos azoles no tienen actividad en las biopelículas fúngicas. Sin embargo, la micafungina y las otras equinocandinas son muy activas en las biopelículas de Candida albicans, Candida dubliniensis, Candida glabrata y Candida krusei, mientras que su actividad es variable con las de Candida parapsilosis y Candida tropicalis. Sin embar- go, su actividad es prácticamente nula contra las biopelículas de Cryptococcus y Trichosporon. Conclusiones: La actividad antifúngica de la micafungina en las biopelículas de Candida refuerza su indicación terapéutica en el tratamiento de las candidemias y candidiasis invasoras asociadas a catéteres, prótesis y otros implantes biomédicos (AU)

Background: Most recalcitrant infections are associated to colonization and microbial biofilm development. These biofilms are difficult to eliminate by the immune response mechanisms and the current antimicrobial therapy. Aim: To describe the antifungal of micafungin against fungal biofilms based in the scientific and medical literature of recent years. Methods: We have done a bibliographic retrieval using the scientific terms “micafungin”, “activity”, “biofilm”, “Candida”, “Aspergillus”, “fungi”, “mycos”*, susceptibility, in PubMed/Medline from the National Library of Medicine from 2006 to 2009. Results: Most current antifungal agents (amphotericin B and fluconazole) and the new azole antifungals have no activity against fungal biofilms. However, micafungin and the rest of echinocandins are very active against Candida albicans, Candida dubliniensis, Candida glabrata, and Candida krusei biofilms but their activities are variable and less strong against Candida tropicalis and Candida parapsilosis biofilms. Moreover, they have not activities against the biofilms of Cryptococcus y Trichosporon. Conclusions: The activity of micafungin against Candida biofilms gives more strength to its therapeutic indication for candidaemia and invasive candidiasis associated to catheter, prosthesis and other biomedical devices (AU)

Monoclonal antibody-based method for measuring olive pollen major allergen Ole e 1.

BACKGROUND: Olive tree pollen is an important cause of inhalant allergy in Mediterranean countries. The major allergen of this pollen, Ole e 1, has caused reactions in the sera of >80% of olive-sensitive patients. Accurate standardization of allergenic products for diagnosis and immunotherapy is essential to guarantee their quality, and measurement of the major allergen content is becoming an important aspect of standardization procedures. OBJECTIVE: To develop a two-site enzyme-linked immunoadsorbent assay (ELISA) for the quantification of Ole e 1. METHODS: BALB/c mice were immunized with purified natural Ole e 1. After fusion and screening by direct ELISA, one of the monoclonal antibodies (5A3) was selected as the capture antibody in an ELISA for Ole e 1 quantification. Bound allergens were detected by a combination of biotinylated Ole e 1-specific polyclonal rabbit antibody and peroxidase-conjugated streptavidin. This ELISA was subsequently evaluated and compared with other techniques. RESULTS: The developed ELISA was highly reproducible and sensitive, with a detection limit of 0.5 ng/mL and a practical range of 1 to 10 ng/mL. The Ole e 1 content ranged from 3 to 50% of the total protein among the nine Olea europaea pollen extracts studied. The assay also detected Ole e 1-like proteins in pollen from other Oleaceae. Correlation was good between the Ole e 1 content determined by ELISA and scanning densitometry and the immunoglobulin E-binding activity of the extracts. CONCLUSION: The described Ole e 1 ELISA is sensitive, reproducible, specific, and reliable, and therefore, can be helpful for standardization of olive pollen extracts intended for clinical use.