Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans . Experimentally, resistance usually arises as a result of mutations in the sterol biosynthesis pathway. Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. Multidrug-resistance (MDR) genes can also play a role in reducing cellular levels of the drug. As azole antifungals all act at the same point in the sterol pathway, resistant isolates are normally cross-resistant to all members of the azole family.  
Therefore, patients receiving a large dose of any potent topical steroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests, and for impairment of thermal homeostasis. If HPA axis suppression or elevation of the body temperature occurs, an attempt should be made to withdraw the drug, to reduce the frequency of application, substitute a less potent steroid, or use a sequential approach when utilizing the occlusive technique.