Synergistic effect of hydralazine associated with triazoles on Candida spp. in planktonic cells.

Objective: To evaluate the antifungal activity of hydralazine hydrochloride alone and in synergy with azoles against Candida spp. and the action mechanism. Methods: We used broth microdilution assays to determine the MIC, checkerboard assays to investigate synergism, and flow cytometry and molecular docking tests to ascertain action mechanism. Results: Hydralazine alone had antifungal activity in the range of 16-128 µg/ml and synergistic effect with itraconazole versus 100% of the fungal isolates, while there was synergy with fluconazole against 11.11% of the isolates. There was molecular interaction with the receptors exo-B(1,3)-glucanase and CYP51, causing reduced cell viability and DNA damage. Conclusion: Hydralazine is synergistic with itraconazole and triggers cell death of Candida spp. at low concentrations, demonstrating antifungal potential.

Antifungal activity of dexamethasone against fluconazole-resistant Candida albicans and its activity against biofilms.

Objective: The present study investigated the antifungal action of dexamethasone disodium phosphate (Dex). Methodology: Susceptibility testing was performed using the Clinical & Laboratory Standards Institute protocol; M27-A3, checkerboard test and biofilm were evaluated with two isolates of Candida albicans, hyphal production test, molecular docking analysis and flow cytometry analysis. Result: Dex and fluconazole (FLC) together had a synergistic effect. Mature biofilm was reduced when treated with Dex alone or in combination. Dex and FLC promoted a decrease in the production of hyphae and changes in the level of mitochondrial depolarization, increased generation of reactive oxygen species, loss of membrane integrity, increased phosphatidylserine externalization and molecular docking; there was interaction with ALS3 and SAP5 targets. Conclusion: Dex showed antifungal activity against FLC-resistant C. albicans strains.

This study aimed to evaluate the antifungal action of dexamethasone against FLC-resistant C. albicans strains.

Synergistic activity of dobutamine combined with azoles and its mechanism of action against strains of Candida glabrata.

Aims: To evaluate the antifungal effect of dobutamine against Candida glabrata as well as its synergism with azoles and its action on biofilm. Methods: The M27-A3 protocol and flow cytometry were used for elucidation of the possible mechanism of action. Results: The tested isolates presented MICs ranging from 2 to 32 µg/ml for dobutamine, with fungistatic effect. A total of 82% of the strains showed synergism with fluconazole, with 90% showing synergism with itraconazole. The effect on biofilm formation was nonsignificant. Cytometry tests showed that dobutamine induced mitochondrial depolarization. Conclusion: Dobutamine has an antifungal effect on strains of C. glabrata and synergistic activity with azoles. This effect is probably mediated by increased oxidative damage to the membrane.

Synergistic activity of diclofenac sodium with oxacillin against planktonic cells and biofilm of methicillin-resistant Staphylococcus aureus strains.

Aim: To evaluate the activity of diclofenac sodium and synergism with oxacillin against clinical strains of SARM in plactonic cells, antibiofilm and biofilm. Materials & methods: Synergism activity was assessed using the fractional inhibitory concentration index and its possible mechanism of action by flow cytometry. Results: The synergistic activity of diclofenac sodium with oxacillin was observed against plactonic cells, antibiofilm and in biofilm formed from clinical methicillin-resistant Staphylococcus aureus strains. Conclusion: This combination caused damage to the integrity of the membrane and ruptures in the DNA of the cells, leading to apoptosis.

Synergistic anticandidal activity of etomidate and azoles against clinical fluconazole-resistant Candida isolates.

Aim: The purpose of this study was to evaluate the effect of etomidate alone and in combination with azoles on resistant strains of Candida spp. in both planktonic cells and biofilms. Materials & methods: The antifungal activity of etomidate was assessed by the broth microdilution test; flow cytometric procedures to measure fungal viability, mitochondrial transmembrane potential, free radical generation and cell death; as well detection of DNA damage using the comet assay. The interaction between etomidate and antifungal drugs (itraconazole and fluconazole) was evaluated by the checkerboard assay. Results: Etomidate showed antifungal activity against resistant strains of Candida spp. in planktonic cells and biofilms. Etomidate also presented synergism with fluconazole and itraconazole in planktonic cells and biofilms. Conclusion: Etomidate showed antifungal activity against Candida spp., indicating that it is a possible therapeutic alternative.