Drug resistance in fungi – an emerging problem

Over the past quarter of a century, invasive fungal infections have emerged as an important cause of morbidity and mortality in immunocompromised patients. Although several new antifungal drugs have been licensed in recent years, antifungal drug resistance is becoming a major concern during treatment of such patients. The resistance may be intrinsic, acquired or clinical. The understanding of the mechanism of resistance and clinical impact is important while planning treatment strategies. Four altered gene expression pathways have been identified in azole resistance. The mechanism of resistance in polyene and echinocandins is still not clearly understood. Recent studies have revealed that molecular chaperone heat shock protein (Hsp90) can alter the relationship between genotype and phenotype leading to a profound impact on antifungal drug resistance. Though definite progress has been made to correlate standardized in vitro antifungal susceptibility testing with prediction of treatment outcome, limitations still exist due to time required for testing and understanding the factors leading to clinical resistance. Overall, the level of resistance to antifungal agents is still relatively low, but there is a possibility of antifungal resistance becoming a crucial determinant of outcome following antifungal therapy in future.