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11 flashcards

USMLE® Step 2 style questions USMLE

1 questions

A 45-year-old man comes to the emergency department with a 24 hour history of fevers and chills. History reveals the patient is taking several chemotherapy drugs for leukemia. His temperature 102ºF (38.9ºC), pulse is 125/min, respirations are 18/min and blood pressure is 120/70 mm Hg. Physical examination shows adrowsy, ill-appearing male with a chemotherapy port in the left chest that is mildly erythematous and warm to the touch. Laboratory analysis reveals an absolute neutrophil count of 280/mm3 (0.28 x 109/L). Blood culture results are currently pending. Despite appropriate empiric treatment, the patient's fever persists for six days. Which is the next best step in management for this patient?

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Yifan Xiao, MD

The “azole” antifungals are a family of medications used to treat mycoses, or fungal infections.

Mycoses can be superficial, like on the skin or hair, or develop into systemic infections in immunodeficient people.

Antifungals work either through fungistatic action, meaning that they inhibit fungal growth, or through fungicidal action, meaning they kill the fungi.

Azoles are divided into two major families of antifungals: imidazoles and triazoles.

Most fungal cells have a tough outer cell wall and an inner cell membrane.

The cell membrane is mostly made of phospholipids with some sterol or modified steroid molecules mixed in.

Humans have cholesterol, while fungi have ergosterol.

Both sterol molecules help keep the cell membrane stable at a wide range of temperatures.

Now, the precursor to both molecules is lanosterol.

Fungi have a cytochrome p450 enzyme called fourteen-alpha-demethylase in their mitochondria and endoplasmic reticulums, which converts lanosterol to ergosterol.

Without ergosterol, the structure of the cell membrane will be disrupted.

This will cause membrane-bound proteins, like ion channels, to stop working properly.

The membrane also becomes fragile, which eventually leads to inhibition of fungal growth.

The azole antifungals include imidazoles, like clotrimazole, isoconazole, miconazole, butoconazole, fenticonazole, and ketoconazole; as well as triazoles like fluconazole, itraconazole and voriconazole.

The only difference between the two groups is the imidazoles contain an imidazole ring, while triazoles contain triazole rings.

These medications work by inhibiting the fourteen-alpha-demethylase enzyme.

However, they also inhibit human cytochrome P450 enzymes to a lesser degree.

Because of this, the vast majority of azoles come in topical form, and they’re commonly used to treat superficial mycoses.

Azole creams are used for treating dermatophytosis, or ringworm, which is a red, itchy, scaly, circular rash, on the feet, groin, or armpit area, caused by Trichophyton fungus.

These fungi are also responsible for the more common “athlete’s foot” or “jock itch”.

Additionally, azoles can be used to treat tinea versicolor, caused by Malassezia globosa.

This disease is characterized by hypopigmentation or hyperpigmentation in patches of skin.

Last but not least, topical azoles are also used to treat yeast infections, such as oral or vaginal candidiasis caused by Candida species.

Topical use of azole antifungals is generally considered to be safe, since absorption through the skin is minimal, and the most common side effect is skin irritation.

Fluconazole is an ergosterol inhibitors antifungal medication that is administered orally or intravenously. It is used to treat a variety of fungal infections, especially Candida infections of the vagina ("yeast infections'), mouth, throat, and bloodstream. It is also used to prevent infections in people with weak immune systems, including those with neutropenia due to cancer chemotherapy, transplant patients, and premature babies. Its mechanism of action involves interfering with synthesis of the fungal cell membrane.
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