Antifungal agents for the treatment of systemic fungal infections in children

Question 1

What major toxicities are associated with amphotericin B?

Answer 1

1. Nephrotoxicity

2. Infusion related events i.e. fever, chills, rigors

Question 2

What is the spectrum of activity for amphotericin B?

Answer 2

Asperigillus fumigatus ++
Aspergillus flavus ++
Candida albicans +++
Candida glabrata ++
Candida lustinaiae +/-
Candida tropicalis +++
Candida krusei ++
Candida parapsilosis +++
Candida gulliermondii ++
Cryptococcus neoformans +++
Fusarium species ++ (lipid products)
Scedosporium apiospermum +/-
Scedosporium prolificans +/-
Zygomycetes +++ (lipid products)
Dermatiaceous moulds +
Dimorphic fungi +++

Question 3

What does amphotericin B not cover?

Answer 3

Aspergillus terreus

Question 4

What is the most common indications for use of amphotericin B?

Answer 4

1. Invasive fungal infections caused by susceptible organisms. 2. Empirical therapy of presumed febrile neutropenic patients

Question 5

What are the major benefits of the lipid preparation of amphotericin B?

Answer 5

Fewer infusion related reactions and nephrotoxicity and broader spectrum of action

Question 6

What are the major side effects of fluconazole?

Answer 6

1. Rare but serious hepatotoxicity

2. Drug interactions as it induces cytochrome p450 isoenzymes

Question 7

What is the action of fluconazole?

Answer 7

Candida more active against albicans then other strains. Can treat cryptococcal agents. No activity against aspergillus or other moulds.

Question 8

What are the indications for fluconazole?

Answer 8

1. Candida infections
2. Cryptococcal infections
3. Antifungal prophylaxis for HSCT patients and neonates

Question 9

What are common adverse effects of itraconazole?

Answer 9

1. abdominal pain
2. vomiting
3. diarrhea
4. elevated liver enzymes
5. drug interactions due to inhibition of cytochrome p450 3A4 enzyme

Question 10

What are the indications for itraconazole?

Answer 10

1. Invasive and non-invasive aspergillosis, oropharyngeal and esophageal candidiasis
2. blastomycosis
3. chronic pulmonary histoplasmosis
4. antifungal prophylaxis in HSCT and lung transplant patients

Question 11

What are the major side effects or voriconazole?

Answer 11

1. Liver function abnormalities
2. Skin rash
3. Visual disturbances
4. Cytochrome P450 isoenzyme drug interactions

Question 12

What are the indications for voriconazole?

Answer 12

1. invasive aspergillosis
2. esophageal candidiasis
3. refractory infections due to scedosporium, angiospermum, and fusarium species

Question 13

What are the major side effects of posaconazole?

Answer 13

1. GI symptoms
2. headaches
3. elevated liver enzymes
4. cytochrome P450 3A4 enzyme drug interactions

Question 14

What are the indications for posaconazole?

Answer 14

1. Aspergillosis in patients intolerant/refractory to other agents
2. Fusariosis in patients intolerant/refractory to other agents
3. Zygomycosis in patients intolerant/refractory to other agents

Question 15

What is the activity of ravuconazole?

Answer 15

Candida species
Aspergillus species
Cryptococcus neoformans
Histoplasma capsulatum
Coccidioides immitis

Question 16

What are the major adverse effects of ravuconazole?

Answer 16

Unclear, appears to be similar to flucoanzole

Question 17

What would be a benefit of ravuconazole?

Answer 17

Long half life of approx. 100h so ideal for step-down therapy and ambulatory treatment

Question 18

How do echinocandins work?

Answer 18

Glucan synthesis inhibitors that specifically inhibit beta-(1-3)-D glucan synthesis, thereby compromising the integrity of the fungal cell wall

Question 19

What are examples of echinocandins?

Answer 19

Caspofungin
Micafungin
Anidulafungin

Question 20

What are the main indications for caspofungin?

Answer 20

1. Candida infections
2. Invasive aspergillosis in patients refractory/intolerant to other therapy
3. Empirical therapy in febrile neutropenic patients

Question 21

What are the main adverse effects for caspofungin?

Answer 21

1. Liver function abnormalities
2. Fever
3. Headache
4. Rash
5. GI symptoms
6. Anemia

Question 22

What are the main indications for micafungin?

Answer 22

Similar to caspofungin prophylaxis of Candida infections in HSCT patients

Question 23

What are the main adverse effects for micafungin?

Answer 23

1. liver function abnormalities
2. nausea
3. vomiting

Question 24

What are the main indications for anidulafungin?

Answer 24

being evaluated for esophageal candidiasis

Question 25

What are the main adverse effects for anidulafungin?

Answer 25

1. Phlebitis/thrombophlebitis
2. Fever
3. Headache
4. Nausea
5. Vomiting
6. Rash

Question 26

What are the main indications for flucytosine?

Answer 26

combination therapy with amphotericin B for Candida and cryptococal infections

Question 27

What are the main adverse effects for flucytosine?

Answer 27

1. GI intolerance
2. bone marrow suppression
3. Rash
4. Hepatotoxicity
5. Headache
6. Confusion
7. Hallucinations
8. Sedation
9. Euphoria