Microbiology
Because fungi have faster mutation rates than bacteria and quickly develop resistance to any drug designed to be selectively toxic to them, making initial selectivity essentially impossible in clinical practice.
Because fungi are eukaryotes and share many cellular structures and biochemical pathways with human cells, reducing the number of unique drug targets.
Because fungal pathogens are always intracellular parasites and therefore any drug that reaches the fungus must also penetrate human cells, causing unavoidable host toxicity unless the drug is completely nonreactive with human enzymes.
Because the immune system neutralizes antifungal drugs through antibody binding and drug clearance pathways that are unique to fungal antigens but shared with host tissues, blunting selective toxicity.
