Activity of antifungal agents alone and in combination against echinocandin-susceptible and -resistant Candida parapsilosis strains / Actividad de antifúngicos solos y en combinación frente a cepas de Candida parapsilosis resistentes y sensibles a equinocandinas

Background: Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options. Aims: The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2 μg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8 μg/ml), (3) caspofungin-resistant strains (MIC ≥ 8 μg/ml), and (4) micafungin-resistant strains (MIC ≥ 8 μg/ml). Methods: Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done. Results: The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible. Conclusions: Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents

Antecedentes: Candida parapsilosis puede volverse resistente a las equinocandinas, lo que requiere la búsqueda de nuevas opciones terapéuticas. Objetivos: El presente estudio tenía como objetivo evaluar la actividad in vitro de algunos antifúngicos, solos y en combinación, frente a cuatro grupos de cepas de C. parapsilosis: 1) cepas clínicas sensibles a las equinocandinas (SE) (CIM ≤ 2 μg/ml), 2) cepas resistentes a la anidulafungina (CIM ≥ 8 μg/ml), 3) cepas resistentes a la caspofungina (CIM ≥ 8 μg/ml) y 4) cepas resistentes a la micafungina (CIM ≥ 8 μg/ml). Métodos: Se evaluaron las interacciones de los antifúngicos con el método de microdilución en damero. También se determinó el valor de la CIM de cada cepa en cada antifúngico de acuerdo con los documentos Clinical and Laboratory Standards Institute M27 (2017) y M60 (2017). Resultados: Las cepas resistentes a las equinocandinas (RE) presentaron los valores de CIM más altos a los antifúngicos probados que las cepas SE a excepción de la anfotericina B, frente a la cual los grupos RE se mantuvieron sensibles. Conclusiones: La mayoría de las combinaciones evidenciaron interacciones indiferentes. El uso de monoterapias aún parece la mejor opción. Puesto que la resistencia a las equinocandinas es un fenómeno emergente, se requieren estudios adicionales con el fin de proporcionar una información más clara acerca de las diferencias de sensibilidad de diferentes cepas a estos antifúngicos

Antifungal activities of diphenyl diselenide and ebselen against echinocandin-susceptible and -resistant strains of Candida parapsilosis.

We evaluated the in vitro antifungal activity of diphenyl diselenide and ebselen against echinocandin-susceptible and -resistant strains of Candida parapsilosis using the broth microdilution method. Diphenyl diselenide (MIC range =1-8 µg/mL) and ebselen (MIC range =0.25-4 µg/mL) showed in vitro activity against echinocandin-susceptible isolates. However, ebselen also showed the highest antifungal activity against echinocandin-resistant strains (MIC range =0.06-4 µg/mL). This study demonstrated that the antifungal potential of diphenyl diselenide and ebselen deserves further investigation using in vivo experimental protocols.

In vitro synergistic combinations of pentamidine, polymyxin B, tigecycline and tobramycin with antifungal agents against Fusarium spp.

The genus Fusarium is characterized by hyaline filamentous fungi that cause infections predominantly in immunocompromised patients. The remarkable primary resistance to antifungal agents of this genus requires a search for new therapeutic possibilities. This study assessed the in vitro susceptibility of 25 clinical isolates of Fusarium against antifungal agents (amphotericin B, caspofungin, itraconazole and voriconazole) and antimicrobials (pentamidine, polymyxin B, tigecycline and tobramycin) according to the broth microdilution method (M38-A2). The interactions between antifungal and antimicrobial agents were evaluated by the microdilution checkerboard method. Pentamidine and polymyxin B showed MIC values ≥4 µg ml-1 against Fusarium spp. The highest rates of synergism were observed when amphotericin B or voriconazole was combined with tobramycin (80 % and 76 %, respectively), polymyxin B (76 % and 64 %) and pentamidine (72 % and 68 %). The most significant combinations deserve in vivo evaluations in order to verify their potential in the treatment of fusariosis.