Antifungal agents for the treatment of systemic fungal infections in children Flashcards
What major toxicities are associated with amphotericin B?
- Nephrotoxicity
2. Infusion related events i.e. fever, chills, rigors
What is the spectrum of activity for amphotericin B?
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 +++
What does amphotericin B not cover?
Aspergillus terreus
What is the most common indications for use of amphotericin B?
- Invasive fungal infections caused by susceptible organisms. 2. Empirical therapy of presumed febrile neutropenic patients
What are the major benefits of the lipid preparation of amphotericin B?
Fewer infusion related reactions and nephrotoxicity and broader spectrum of action
What are the major side effects of fluconazole?
- Rare but serious hepatotoxicity
2. Drug interactions as it induces cytochrome p450 isoenzymes
What is the action of fluconazole?
Candida more active against albicans then other strains. Can treat cryptococcal agents. No activity against aspergillus or other moulds.
What are the indications for fluconazole?
- Candida infections
- Cryptococcal infections
- Antifungal prophylaxis for HSCT patients and neonates
What are common adverse effects of itraconazole?
- abdominal pain
- vomiting
- diarrhea
- elevated liver enzymes
- drug interactions due to inhibition of cytochrome p450 3A4 enzyme
What are the indications for itraconazole?
- Invasive and non-invasive aspergillosis, oropharyngeal and esophageal candidiasis
- blastomycosis
- chronic pulmonary histoplasmosis
- antifungal prophylaxis in HSCT and lung transplant patients
What are the major side effects or voriconazole?
- Liver function abnormalities
- Skin rash
- Visual disturbances
- Cytochrome P450 isoenzyme drug interactions
What are the indications for voriconazole?
- invasive aspergillosis
- esophageal candidiasis
- refractory infections due to scedosporium, angiospermum, and fusarium species
What are the major side effects of posaconazole?
- GI symptoms
- headaches
- elevated liver enzymes
- cytochrome P450 3A4 enzyme drug interactions
What are the indications for posaconazole?
- Aspergillosis in patients intolerant/refractory to other agents
- Fusariosis in patients intolerant/refractory to other agents
- Zygomycosis in patients intolerant/refractory to other agents
What is the activity of ravuconazole?
Candida species Aspergillus species Cryptococcus neoformans Histoplasma capsulatum Coccidioides immitis
What are the major adverse effects of ravuconazole?
Unclear, appears to be similar to flucoanzole
What would be a benefit of ravuconazole?
Long half life of approx. 100h so ideal for step-down therapy and ambulatory treatment
How do echinocandins work?
Glucan synthesis inhibitors that specifically inhibit beta-(1-3)-D glucan synthesis, thereby compromising the integrity of the fungal cell wall
What are examples of echinocandins?
Caspofungin
Micafungin
Anidulafungin
What are the main indications for caspofungin?
- Candida infections
- Invasive aspergillosis in patients refractory/intolerant to other therapy
- Empirical therapy in febrile neutropenic patients
What are the main adverse effects for caspofungin?
- Liver function abnormalities
- Fever
- Headache
- Rash
- GI symptoms
- Anemia
What are the main indications for micafungin?
Similar to caspofungin prophylaxis of Candida infections in HSCT patients
What are the main adverse effects for micafungin?
- liver function abnormalities
- nausea
- vomiting
What are the main indications for anidulafungin?
being evaluated for esophageal candidiasis
