Antifungals For Systemic Infections Flashcards
What are some examples of lipid based amphotericin B and what are the advantages?
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
What is unique about fluconazole?
Low lipophilic nature - readily penetrates tissue
Limited protein binding - 90% bioavailability
Concentrates in the urine
What is the main concerning side effect of fluconazole?
Hepatotoxicity
What must you consider when you put someone of fluconazole or itraconazole apart from liver function?
Drug interactions: it induces cytochrome P450 isoenzymes
What are the clinical uses of fluconazole?
Most widely used antifungal.
Candida - especially active versus Candida albicans
Cryptococcal infections
Prophylactic agents for allogenic stem cell transplants and ELBW neonates
Are there any bugs that fluconazole cannot treat?
Aspergillus species and moulds
Are there any kids in whom itraconazole shouldn’t been used?
Kids
What are some side effects of itraconazole?
GI upset - the oral route causes GI intolerance (AP, diarrhea, vomiting) from osmotic properties
Elevated liver enzymes
What are the clinical indications of itraconazole?
2
Useful if you want to prevent candida and Aspergillus - stem cell transplants or transplant patients colonized with Aspergillus
Severe Aspergillus infection
What are the side effects of voriconazole?
5
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
What makes the use of voriconazole challenging?
Variable plasma levels in kids because kids eliminate it better than adults
What are the clinical indications for voriconazole?
2
Treatment of invasive Aspergillus especially with pulmonary findings
2nd line for treating systemic candida infections (after fluconazole)
What are the clinical indications for Posaconazole?
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.
What is unique about ravuconazole?
Very long half life (100h) so it is ideal for ambulatory treatment
Which bugs can ravuconazole treat?
5
Candida species Aspergillus species Cryptococcosis species Histoplasmosis capsulatum Coccidioides immitis
Who do echinocandins work (caspofungin) ?
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
How is caspofungin dosed?
per BSA: 50mg/m2/day
Young kids eliminate it more readily
What are the clinical indications for caspofungin?
Invasive candida
Invasive Aspergillus - especially pulmonary
If renal impairment restricts use of other antifungals
How do you dose micafungin?
0.5 - 4 mg/kg/day
Clearance is greater in older kids
What is special about anidulafungin?
Longest half life of all the echinocandins - 18 hours so it is dosed once daily
Concentrates in the lung and liver
What are the side effects of flucytosine?
GI Intolerance and bone marrow suppression are common Rash Hepatotoxicity Headache Confusion Hallucinations Sedation Euphoria
Can you use it in combination with amphotericin B?
If you really want to BUT flucytosine potentials the renal toxicities of amphoricin B and decreases elimination of flucytosine thus potentiality its toxicity
What is flucytosine used?
Often in combination with amphotericin B for candida or cryptococcal infections, especially in the CNS
Is combination therapy Better than monotherapy for antifungals?
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
How does flucytosine work?
It is an anti metabolite
What are the main side effects of amphotericin B?
2
Nephrotoxicity
Infusion-related events - fevers, chills, rigors
NB newer agents are more lipid based and this less nephrotoxic
