Antifungals: systemic use Flashcards
What is the first-line drug for aspergillosis? (2 options)
Voriconazole (treatment of choice)
OR
Liposomal amphotericin B
Second line: Caspofungin OR itraconzaole
Third line: Posaconazole
What are the indications for voriconazole?
- Invasive aspergillosis
- Scedosporium spp. (serious infection)
- Fusarium spp. (serious infection)
- Invasive fluconazole-resistant Candida spp. (including C. krusei)
https://bnf.nice.org.uk/drug/voriconazole.html
What is the dose of oral voriconazole for the treatment of invasive aspergillosis for a patient with bodyweight < 40 kg?
Initially 200 mg every 12 hours for 2 doses, then 100 mg every 12 hours, increased if necessary to 150 mg every 12 hours
Bodyweight 40 kg or above:
- Initially 400 mg every 12 hours for 2 doses, then 200 mg every 12 hours, increased to 300 mg every 12 hours
What is the dose of oral voriconazole for the treatment of invasive aspergillosis for a patient with bodyweight of 40 kg or above?
Initially 400 mg every 12 hours for 2 doses, then 200 mg every 12 hours, increased to 300 mg every 12 hours
Bodyweight < 40 kg:
- Initially 200 mg every 12 hours for 2 doses, then 100 mg every 12 hours, increased if necessary to 150 mg every 12 hours
What is the dose of IV infusion of voriconazole for the treatment of invasive aspergillosis?
Initially 6 mg/kg every 12 hours for 2 doses, then 4 mg/kg every 12 hours; reduced if not tolerated to 3 mg/kg every 12 hours
For max. 6 months
Can also be given orally
Which antifungal drug can be used as an adjunct to glucocorticoids in the treatment of allergic bronchopulmonary aspergillosis?
Itraconazole
Which oral medications can be used to treat vaginal candidiasis? (2 - first and second line)
First line**: Fluconazole
- 150 mg for 1 dose
Second line: Itraconazole (for resistant organisms in adults)
- 200 mg twice daily for 1 day
**The other first line is a locally acting antifungal (e.g. clotrimazole pessary)
Which oral medications can be used to treat oropharyngeal candidiasis if unresponsive to topical therapy? (2 - first and second line)
First line: Fluconazole
- 50 mg daily for 7-14 days
Second line: Itraconazole
- 100-200 mg twice daily for 2 weeks
Which class of oral medications are used to treat oropharyngeal candidiasis in immunocompromised patients?
Triazole (fluconazole, itraconazole)
What are the two first-line options for invasive or disseminated candidiasis?
Echinocandin
OR
Fluconazole (only in clinically stable patients who have not received an azole antifungal recently)
Second line:
Amphotericin B
What is the first-line treatment for CNS candidiasis?
Amphotericin B
What is the treatment of choice for cryptococcal meningitis? (2 drugs initially, followed by 1)
Amphotericin B (IV) and Flucytosine (IV) for 2 weeks
Followed by fluconazole (oral) for 8 weeks (or until cultures are negative)
Which antifungal treatment can be used as prophylaxis following successful treatment of cryptococcal meningitis in HIV-infected patients?
Fluconazole
- 200 mg daily
What is the first-line treatment of indolent non-meningeal histoplasmosis infection (e.g. chronic pulmonary histoplasmosis) in an immunocompetent patient?
Itraconazole
- 200 mg 3 times a day for 3 days, then 200 mg 1-2 times a day (oral) OR
- 200 mg every 12 hours for 2 days, then 200 mg once daily for max. 12 days (IV)
For the treatment of histoplasmosis, what are the routes of administration for itraconazole? (2)
Oral
- 200mg 3 times a day for 3 days, then 200 mg 1-2 times a day
OR
IV
- 200 mg every 12 hours 2 days, then 200 mg once daily for max. 12 days
What drug is used in the initial treatment of fulminant or severe histoplasmosis infections?
Amphotericin B (IV)
Followed by itraconazole (oral)
What drug is used as prophylaxis against a relapse of histoplasmosis infection in immunosuppressed patients?
Itraconazole (oral)
- 200 mg once daily, then increased to 200 mg twice daily
Mild localised fungal infections of the skin usually respond to topical therapy. What are the indications for systemic therapy used fungal skin infections?
- Topical therapy fails
- Many areas are affected
- Site of infection is difficult to treat (nails, scalp)
Frequently used options: oral imidazole, triazole antifungals (e.g. itraconazole), terbinafine
Less commonly used: griseofulvin
In which two anatomical locations do localised fungal infections of the skin require systemic therapy?
- Nail (onychomycosis)
- Scalp (tinea capitis)
Frequently used options: oral imidazole, triazole antifungals (e.g. itraconazole), terbinafine
Less commonly used: griseofulvin
Which oral antifungal is NOT effective against pityriasis versicolour?
Terbinafine
Topical therapy (ketaconazole shampoo) has been ineffective for a patient with pityriasis versicolour, which two oral antifungals can be used?
Itraconazole
- 200 mg once daily for 7 days
OR
Fluconazole
- 50 mg daily for 2-4 weeks (max. 6 weeks)
What is the first-line drug for the systemic treatment of skin and nail infections?
Terbinafine
- 250mg once daily (varying length of treatment depending on location of fungal infection)
Second line: itraconazole
Less commonly used: griseofulvin
For the treatment of onychomycosis, 200 mg of itraconazole can either be givenonce daily for 3 months or as intermittent ‘pulse’ therapy. What is intermittent ‘pulse’ therapy?
200 mg twice daily for 7 days, subsequent courses repeated after 21-day intervals
(fingernails 2 courses, toenails, 3 courses)
BUT treatment of choice (first-line) is terbinafine
What class of antifungal drugs are preferred as prophylaxis for immunocompromised patients?
Triazole antifungals (oral) e.g. Fluconazole, itraconazole
When choosing an antifungal drug for prophylaxis in immunocompromised patients, it is important to take into consideration:
(Fluconazole/itraconazole) is more reliable absorbed than (fluconazole/itraconazole), but (fluconazole/itraconazole) is NOT effective against Aspergillus spp.
Fluconazole is more reliable absorbed than itraconazole, but fluconazole is NOT effective against Aspergillus spp.
Itraconazole is preferred in patients at risk of invasive aspergillosis
Which antifungal is preferred in immunocompromised patients at risk of invasive aspergillosis?
Itraconazole
Because fluconazole is not effective against Asperigllus spp.
Which antifungal drug can be given as prophylaxis in patients undergoing haematopoietic stem cell transplantation or receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome and expected to develop prolonged neutropenia?
Posaconazole
- 200 mg three times a day, start several days before the expected onset of neutropenia and continue for 7 dyas after neutrophil count rises above 500 cells/mm3
Which drug can be be used as prophylaxis of candidiasis in patients undergoing haematopoietic stem cell transplantation when fluconazole, itraconazole or posaconazole cannot be used?
Micafungin
- 1 mg/kg once daily continue for at least 7 days after neutrophil count is desirable (bodyweight up to 40 kg)
- 50 mg once daily continue for at least 7 days after neutrophil count is in desirable range (bodyweight 40 kg or above)
Which triazole antifungal drug has good penetration into the cerebrospinal fluid to treat fungal meningitis?
Fluconazole
Why can fluconazole be used to treat candiduria?
Excreted largely unchanged in the urine
Itraconazole should be avoided or used with caution in patients with what disease?
Liver disease
Fluconazole is less frequently associated with hepatotoxicity
Voriconazole is a broad-spectrum antifungal drug that is licensed for use in …
life-threatening infections
Name 4 triazole antifungals
Fluconazole
Itraconazole
Posaconazole
Voriconazole
When would you consider using posaconazole for treatment of invasive fungal infections?
If the infection is unresponsive to conventional treatment
e.g. unresponsive to itraconazole, amphotericin B, fluconazole
Name 4 imidazole antifungals that can be used for local treatment of vaginal candidiasis and for dermatophyte infections
Clotrimazole
Econazole nitrate
Ketaconazole
Tioconazole
Which imidazole antifungal is given in oral gel form for the treatment for oral and intestinal candidiasis?
Miconazole
Name 2 polyene antifungals
Amphotericin B
Nystatin
What are the indications for the use of nystatin? (2)
Oral candidiasis (oral) Oral and perioral fungal infections (oral)
What is the mode of administration of nystatin?
Local application in the mouth
AmBisome is the trade name for which antifungal drug?
Liposomal amphotericin B
[Abelcet = amphotericin B (lipid complex)]
Abelcet is the trade name for which antifungal drug?
Amphotericin B (lipid complex)
Which 2 organs are commonly damaged by amphotericin B?
- Kidneys
- nephrotoxicity
- nephrocalcinosis
- renal impairment
- renal tubular acidosis
- hyposthenuria - Liver
- hepatic function abnormal (discontinue use)
Name 3 echinocandin antifungal drugs?
Anidulafungin
Caspofungin
Micafungin
Which two fungal species can caspofungin be used to treat?
Aspergillus spp.
Candida spp.
Caspofungin is an echinocandin antifungal
Which fungal species can both anidulafungin and micafungin be used to treat?
Candida spp.
Anidulafungin and micafungin are both echinocandin antifungals
Are the echinocandins, anidulafungin and micafungin, used in the treatment of aspergillosis?
NO
Caspofungin is the only echinocandin that is used in the treatment of aspergillosis
Are echinocandins effective against fungal infections of the CNS?
NO
Which echinocandin antifungal is used in the treatment of both Aspergillus spp. and Candida spp.?
Caspofungin
What drug can be used in combination with flucytosine due to the synergistic effect?
Amphotericin B
What needs to be monitored weekly when taking flucytosine? (2)
Kidney function tests
Blood counts
What are the indications for the use of flucytosine? (3)
- Systemic yeast and fungal infections
- Adjunct to amphotericin B in severe systemic candidiasis and other severe or long-standing infections
- Cryptococcal meningitis (adjunct to amphotericin B)
Griseofulvin is the drug of choice for which infection in children?
Trichophyton infections in children
