Infection: Antifungals, systemic use

Question 1

Aspergillosis most commonly affects what? What is the exception?

Answer 1

Most commonly affects the respiratory tract but in severly immunocompromised patients, invasive forms can affect the heart, brain, and skin.

Question 2

What is the treatment of choice for aspergillosis?

Answer 2

Voriconazole, however liposomal amphotericin is an alternative first-line treatment when voriconazole cannot be used.

Question 3

What is the second line treatment of aspergillosis if voriconazole cannot be used?

Answer 3

Liposomal amphotericin.
Caspofungin or itraconazole, can be used in patients who are refractory to, or intolerant of voriconazole and liposomal amphotericin.

Question 4

What are the third line treatment options for aspergilosis if voriconazole + liposomal amphotericin are contra-indicated?

Answer 4

Caspofungin or itranconazole.

Question 5

Posaconazole is licensed for use in aspergillosis in what circumstances?

Answer 5

INVASIVE aspergillosis and intolerance of itraconazole and amphotericin.

Question 6

Vaginal candidiasis unresponsive to oral fluconazole can be treated with:

Answer 6

Itraconazole oral.

Question 7

For invasive or disseminated candidiasis, what is used?

Answer 7

An echinocandin.

Question 8

What is the most common form of fungal menigitis?

What patient groups is it seen in typically?

Answer 8

Cryptococcosis is uncommon but infection in the immunocompromised, especially in HIV-positive patients, can be life-threatening; cryptococcal meningitis.

Question 9

What is the treatment of choice in cryptococcal meningitis?

Answer 9

Amphotericin by intravenous infusion and flucytosine by intravenous infusion for 2 weeks, followed by fluconazole by mouth for 8 weeks or until cultures are negative.

Question 10

Histoplasmosis is rare in temperate climates; it can be life-threatening, particularly in HIV-infected persons. What is the treatment of choice of immunocompetent patients with indolent non-meningeal infection, including chronic pulmonary histoplasmosis?

Answer 10

Itraconazole.

Question 11

When is amphotericin used in the treatment of histoplasmosis considering itraconazole is first-line?

Answer 11

Amphotericin by intravenous infusion is used for the initial treatment of fulminant or severe infections, followed by a course of itraconazole by mouth. Following successful treatment, itraconazole can be used for prophylaxis against relapse until immunity recovers.

Question 12

In the treatment of skin and nail fungal infections, why are oral imidazole or triazole antifungals (itraconazole) and terbinagine used more frequently than griseofulvin?

Answer 12

They have a broader spectrum of activity and require a shorter duration of treatment.

Question 13

What is tinea capitis?

Answer 13

Ringworm of scalp, needs systemic treatment although topical application of an antifungal may reduce transmission. Griseofulvin is used in adults and children.

Question 14

Amphotericin by intravenous infusion and flucytosine by intravenous infusion for 2 weeks, followed by fluconazole by mouth for 8 weeks or until cultures are negative. Treatment of choice for:

Answer 14

Cryotoccal meningitis

Question 15

How is tinea capitis treated?

Answer 15

Griseofulvin

Question 16

What is pityriasis versicolor?

Answer 16

Also known as tinea versicolor, a common condition that causes small patches of skin to become scaly and discoloured.

Occurs a lot in moist, warm places.
Caused by a yeast called Malassezia.

ketocoazole shampoo

Question 17

How is pityriasis versicolor treated?

Answer 17

Itraconazole by mouth or fluconazole by mouth.

ketoconazole shampoo

Oral terbinafine is not effective for pityriasis versicolor.

Question 18

Immunocompromised patients are at particular risk of fungal infections and may receive antifungal drugs prophylactically. What are the drugs of choice?

Answer 18

Oral triazole antifungals:
Fluconazole is more reliably absorbed than itraconazole, but fluconazole is not effective against Aspergillus spp. so itraconazole is preferred in patients at risk of aspergillosis.

Question 19

Why is itraconazole preferred over fluconazole in the prophylaxis of aspergillus infections of the immunocompromised?

Answer 19

Fluconazole is not active against Aspergillus spp.

Question 20

What are the four main classes of antifungals (and examples)?

Answer 20

1. Triazole antifungals: fluconazole, itraconazole, posaconazole, voriconazole.
2. Imidazole antifungals: clotrimazole, econazole nitrate, ketoconazole and tioconazole, miconazole.
3. Polyene antifungals: amphotericin and nystatin.
4. Echinocandin: anidulafungin, caspofungin and micafungin.

Question 21

What are the triazole antifungals?

Answer 21

Fluconazole
Itraconazole
Posaconazole
Voriconazole

Question 22

What are the imidazole antifungals?

Answer 22

Clotrimazole
Econazole
Ketoconazole
Miconazole

Question 23

What are the polyene antifungals?

Answer 23

Amphotericin
Nystatin
Neither systemically available via mouth

Question 24

What are the echinocandin antifungals?

Answer 24

Anidulafungin
Caspofungin
Micafungin

Question 25

Other than the four main classess of antifungal agent (triazole, imidazole, polyene and echinocandin) what others exist? (3)

Answer 25

Flucytosine
Griseofulvin
Terbinafine

Question 26

What does fluconazoles absorption and excretion characteristics mean for its clinical uses?

Answer 26

Fluconazole is very well absorbed after oral administration. It also achieves good penetration into the cerebrospinal fluid to treat fungal meningitis. Fluconazole is excreted largely unchanged in the urine and can be used to treat candiduria.

Question 27

Which triazole antifungal is cautioned in people with liver disease?

Answer 27

Itraconazole has been associated with liver damage and should be avoided or used with caution in patients with liver disease; fluconazole is less frequently associated with hepatotoxicity.

Question 28

Which triazole antifungal requires an acid environment in the stomach for optimal absorption?

Answer 28

Itraconazole capsules require an acid environment in the stomach for optimal absorption.

Question 29

Clotrimazole is mostly only effective against

Answer 29

Candida albicans

Question 30

What imidazole antifungal can be used for oral thrush?

Answer 30

Miconazole, daktarin oral gel.

Question 31

What are the uses of the polyene antifungal nystatin?

Answer 31

Oral, oropharyngeal, and perioral infections by local application in the mouth.

Nystatin is also used for Candida albicans infection of the skin.

Question 32

Why do lipid formulations of amphotericin (polyene antifungal) exist?

Answer 32

When given parenterally amphotericin is toxic and side-effects are common. Lipid formulations of amphotericin (Abelcet® and AmBisome®) are significantly less toxic and are recommended when the conventional formulation of amphotericin is contra-indicated because of toxicity, especially nephrotoxicity or when response to conventional amphotericin is inadequate; lipid formulations are more expensive.

Question 33

The echinocandin antifungals anidulafungin, caspofungin and micafungin are only active against what?

Answer 33

Aspergillus spp. and Candida spp.

However, anidalufungin and micafungin are NOT used for asperfillosis.

Question 34

What is the role in therapy of fluctyosine?

Answer 34

Flucytosine is used with amphotericin in a synergistic combination. Bone marrow depression can occur which limits its use, particularly in HIV-positive patients; weekly blood counts are necessary during prolonged therapy. Resistance to flucytosine can develop during therapy and sensitivity testing is essential before and during treatment. Flucytosine has a role in the treatment of systemic candidiasis and cryptococcal meningitis.

Question 35

What are the issues with using flucytosine and amphotericin together?

Answer 35

Flucytosine is used with amphotericin in a synergistic combination. Bone marrow depression can occur which limits its use, particularly in HIV-positive patients; weekly blood counts are necessary during prolonged therapy. Resistance to flucytosine can develop during therapy and sensitivity testing is essential before and during treatment. Flucytosine has a role in the treatment of systemic candidiasis and cryptococcal meningitis.

Question 36

When is griseofulvin used?

Answer 36

Not much anymore, it is effective for widespread or intractable dermatophyte infections but has been superseded by newer antifungals, particularly for nail infections.

Question 37

Terbinafine is the drug of choice for what?

Answer 37

fungal nail infections and is also used for ringworm infections where oral treatment is considered appropriate.

Question 38

What monitoring should accompany the use of oral terbinafine?

Answer 38

Hepatic function before treatment and then periodically after 4-6 weeks.

Discontinue if abnormalities develop.