advanced HIV receiving treatment for thrush or esophageal Candida infection). In C. albicans, resistance occurs by way of mutations in the ERG11 gene, which codes for 14α-demethylase. These mutations prevent the azole drug from binding, while still allowing binding of the enzyme's natural substrate, lanosterol. Development of resistance to one azole in this way will confer resistance to all drugs in the class. 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. Other gene mutations are also known to contribute to development of resistance. C. glabrata develops resistance by up regulating CDR genes, and resistance in C. krusei is mediated by reduced sensitivity of the target enzyme to inhibition by the agent. The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the product data sheet. According to the United States Centers for Disease Control, fluconazole resistance among Candida strains in the U.S. is about 7%. Contraindications Fluconazole is contraindicated in patients who: Drink alcohol have known hypersensitivity to other azole medicines such as ketoconazole; are taking terfenadine, if 400 mg per day multidose of fluconazole is administered; concomitant administration of fluconazole and quinidine, especially when fluconazole is administered in high dosages; take SSRIs such as fluoxetine or sertraline. Side effects Adverse drug reactions associated with fluconazole therapy include: Common (≥1% of patients): rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, and/or elevated liver enzymes Infrequent (0.1–1% of patients): anorexia, fatigue, constipation Rare (<0.1% of patients): oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions Very rare: prolonged QT interval, torsades de pointes FDA is now saying treatment with chronic, high doses of fluconazole during the first trimester of pregnancy may be associated with a rare and distinct set of birth defects in infants. If taken during pregnancy it may result in harm. These cases of harm, however, were only in women who took large doses for most of the first trimester. Fluconazole is secreted in human milk at concentrations similar to plasma. Therefore, the use of fluconazole in lactating mothers is not recommended. Fluconazole therapy has been associated with QT interval prolongation, which may lead to serious cardiac arrhythmias. Thus, it is used with caution in patients with risk factors for prolonged