Antibiotics in Combination with Antifungals to Combat Drug Resistant Candida – A Concept on Drug Repurposing

Abstract

Candida spp. are emerging pathogens of hospital-acquired infections that causes invasive candidiasis, leading to human mortality and morbidity. Evolution of resistance to different groups of antifungal drugs is a major concern nowadays. Resistance mechanism in some of the antifungal drugs are formation of biofilms, alterations in drug target and lowered intracellular drug levels caused by efflux pumps. Introduction of novel strategies are necessitous to eliminate the phenomenon of drug resistance. Drug repurposing is a promising therapeutic strategy that can improve the efficacy of antifungal therapy for invasive candidiasis. Antibiotics and antifungal drugs were combined against resistant Candida spp. and the in vitro antifungal synergy were analyzed by disk diffusion methods, checkerboard microbroth dilution method and time-kill curves. Synergistic effects were seen against drug-resistant strains, but drug-susceptible strains show indifferent effects in experimental studies. Profiting from the synergistic effects of combination therapy, alternative therapeutic approaches for drug resistance could be designed. This review will discuss different antifungal drugs and their mechanism, drug-resistance mechanisms and some of the antibiotic and antifungal combinations that provide novel insights in treating invasive fungal infections.