Antifungals For Systemic Infections

Question 1

What are some examples of lipid based amphotericin B and what are the advantages?

Answer 1

Amphotericin B lipid complex
Liposomal amphotericin B
Amphotericin B colloidal dispersion

Sometimes better tolerated re infusion events - except for the latter which has higher infusions events
Less nephrotoxic - so can use higher doses

Question 2

What is unique about fluconazole?

Answer 2

Low lipophilic nature - readily penetrates tissue
Limited protein binding - 90% bioavailability
Concentrates in the urine

Question 3

What is the main concerning side effect of fluconazole?

Answer 3

Hepatotoxicity

Question 4

What must you consider when you put someone of fluconazole or itraconazole apart from liver function?

Answer 4

Drug interactions: it induces cytochrome P450 isoenzymes

Question 5

What are the clinical uses of fluconazole?

Answer 5

Most widely used antifungal.
Candida - especially active versus Candida albicans
Cryptococcal infections
Prophylactic agents for allogenic stem cell transplants and ELBW neonates

Question 6

Are there any bugs that fluconazole cannot treat?

Answer 6

Aspergillus species and moulds

Question 7

Are there any kids in whom itraconazole shouldn’t been used?

Answer 7

Kids

Question 8

What are some side effects of itraconazole?

Answer 8

GI upset - the oral route causes GI intolerance (AP, diarrhea, vomiting) from osmotic properties
Elevated liver enzymes

Question 9

What are the clinical indications of itraconazole?

2

Answer 9

Useful if you want to prevent candida and Aspergillus - stem cell transplants or transplant patients colonized with Aspergillus
Severe Aspergillus infection

Question 10

What are the side effects of voriconazole?

5

Answer 10

Renal toxicity - the IV formulation should be avoided in kids with Renal impairment because of build up of the solvent
Skin rash
Visual abnormalities - blurred vision, photophobia
Photo sensitivity reactions
Elevated liver enzymes

Question 11

What makes the use of voriconazole challenging?

Answer 11

Variable plasma levels in kids because kids eliminate it better than adults

Question 12

What are the clinical indications for voriconazole?

2

Answer 12

Treatment of invasive Aspergillus especially with pulmonary findings
2nd line for treating systemic candida infections (after fluconazole)

Question 13

What are the clinical indications for Posaconazole?

Answer 13

Pediatric experience is limited
Salvage therapy if the first line antifungal has not worked or is contraindicated:
- Invasive Aspergillosis and zygomycetes infections.
- Prophylactic for stem cell recipients.

Question 14

What is unique about ravuconazole?

Answer 14

Very long half life (100h) so it is ideal for ambulatory treatment

Question 15

Which bugs can ravuconazole treat?

5

Answer 15

Candida species
Aspergillus species
Cryptococcosis species
Histoplasmosis capsulatum
Coccidioides immitis

Question 16

Who do echinocandins work (caspofungin) ?

Answer 16

Glucagon synthesis inhibitors that specifically inhibit beta (1,3)-D-glucagon synthesis - compromising the integrity of the cell wall

NB humans do not have beta D glucagon

Question 17

How is caspofungin dosed?

Answer 17

per BSA: 50mg/m2/day

Young kids eliminate it more readily

Question 18

What are the clinical indications for caspofungin?

Answer 18

Invasive candida
Invasive Aspergillus - especially pulmonary
If renal impairment restricts use of other antifungals

Question 19

How do you dose micafungin?

Answer 19

0.5 - 4 mg/kg/day

Clearance is greater in older kids

Question 20

What is special about anidulafungin?

Answer 20

Longest half life of all the echinocandins - 18 hours so it is dosed once daily
Concentrates in the lung and liver

Question 21

What are the side effects of flucytosine?

Answer 21

GI Intolerance and bone marrow suppression are common
Rash
Hepatotoxicity
Headache
Confusion
Hallucinations
Sedation
Euphoria

Question 22

Can you use it in combination with amphotericin B?

Answer 22

If you really want to BUT flucytosine potentials the renal toxicities of amphoricin B and decreases elimination of flucytosine thus potentiality its toxicity

Question 23

What is flucytosine used?

Answer 23

Often in combination with amphotericin B for candida or cryptococcal infections, especially in the CNS

Question 24

Is combination therapy Better than monotherapy for antifungals?

Answer 24

There is no evidence that combination therapy is better except in cryptococcal meningitis
However experts use combo therapy with the following situations:
- CNS disease
- incomplete response to initial therapy
- very severe disease
- invasive pulmonary aspergillosis especially if near important mediastinal vessels

Question 25

How does flucytosine work?

Answer 25

It is an anti metabolite

Question 26

What are the main side effects of amphotericin B?

2

Answer 26

Nephrotoxicity
Infusion-related events - fevers, chills, rigors

NB newer agents are more lipid based and this less nephrotoxic