Another resistance mechanism employed by both C. albicans and C. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters.

[17] The rising fungal resistance to fluconazole and related azole drugs spurs the need to find effective combative solutions swiftly.

Rising resistance raises concerns since fluconazole is commonly used due to its inexpensiveness and ease of administration, according to the World Health Organization.

[19] Research shows that natural substances can have specified interactions with cell components, increasing the intracellular concentration of associated antifungal drugs and their effectiveness.

For example, Brazilian red propolis, an organic bee liquid, synergizes with fluconazole to combat common yeast infections such as C. parapsilosis and C. glabrata.

The essential oil from Nectandra lanceolata, a tree species native to wet tropical biomes, plays a similar role in ciclopirox, another common antifungal.

[18] While combination therapy offers the benefits of faster and more extensive fungal eradication, including a reduced risk of resistance or tolerance, it also presents challenges.

An alternative to combination therapy for those who had prior exposure to Azoles is antifungal drugs of class echinocandins, recommended as the first method of treatment against invasive candidiasis.

The three echinocandins currently licensed for medical use, namely anidulafungin, caspofungin, and micafungin, are potent against candidiasis, which has grown resistant to fluconazole because of the differences in their action mechanism.

However, resistance to echinocandins can still develop through point mutations within highly conserved regions of the FKS1 and FKS2 genes through the exposure of members of this class.

Phages, viruses that infect microbes including fungi, exhibit potent antimicrobial effects against various resistant fungal strains, demonstrating remarkable specificity and efficacy.

Their unique attributes, such as specificity, potency, compatibility with biological systems, and ability to kill fungi, make them attractive candidates for therapeutic interventions.

However, challenges remain in terms of their production scalability, formulation, stability, and the emergence of fungal resistance, which hinders their widespread adoption.

Capsules contain lactose and should not be given to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption [30] Fluconazole is an inhibitor of the human cytochrome P450 system, particularly the isozyme CYP2C19 (CYP3A4 and CYP2C9 to lesser extent) [31] In theory, therefore, fluconazole decreases the metabolism and increases the concentration of any drug metabolised by these enzymes.

This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cytoplasmic membrane, and subsequent accumulation of 14α-methyl sterols.