FUNGAL INFECTIONS

Question 1

What drugs come under the polyene class?

Answer 1

Amphotericin B

Nystatin

Question 2

What is amphotericin B?

Answer 2

Polyene macrolide - broad spectrum kills most fungi - fungicidal. Used oral or IV
- IV route very toxic so used for life threatening systemic infections e.g. cryoptococcal meningitis

Question 3

What is nystatin?

Answer 3

Polyene macrolide - local or topical (oral suspension) for oral infections and cream for skin candida.
Broad spectrum

Question 4

Mechanism of action of polyenes?

Answer 4

Bind to ergosterol
Form pores in the PM
Leaks K+ / Mg2+ cause . cell cannot maintain ionic balance due to pores
causes cell lysis
Fungicidal depending on conc - note that . high enough concs . will bind to cholesterol too which will affect human cells

Question 5

What drugs come under the azole class?

Answer 5

1. Imidazoles such as miconazole, clotrimazole, ketoconazole
2. Triazoles e.g. fluconazole, itraconazole, voriconazole, posaconazole

Question 6

are triazoles broad spectrum? if so what?

Answer 6

Yes - candida, crytococcusm, aspergillus

Question 7

Mechanism of action of azoles?

Answer 7

Inhibit lanosterol 14-alpha demethylase CYP450 which interferes with ergosterol synthesis and disrupts PM - fungistatic

Question 8

are imidazoles broad spectrum

Answer 8

Yes - dermatophytes and candidasis

Question 9

Brand names for:
miconazole
ketoconazole
clotrimazole

Answer 9

miconazole - daktarin
ketoconazole - nizoral
clotrimazole - canesten

Question 10

What is flucytosine?

Answer 10

Antifungal (synthetic is fluoropyrimidine) - Converted to 5-FU which disrupts DNA/RNA synthesis (competes with uracil for RNA synthesis)

• Fungistatic
• used in combo with other drugs for severe cryptococcal or candida systemic infections

Question 11

Is flucytosine used alone?

Answer 11

No - in combo with others for severe cryptotoccal or candida systemic infect

Question 12

What class is griseofulvin and MoA?

Answer 12

Benzofuran –> binds to polymerised microtubules and inhibits mitosis to stop growth of fungi - thus fungistatic

Question 13

What is the spectrum of griseofulvin?

Answer 13

Limited . - dermatophytes e.g. tinea capitis

Question 14

What are the S/E of griseofulvin?

Answer 14

N&V, anorexia, rash, urticaria

Question 15

What drugs are included in allylamines class and MoA?

Answer 15

Terbinafine (Lamisil) –> mainly on dermatophytes
MoA: inhibits squalene expoxidase to inhibit generation of lanosterol from squalene in ergosterol biosynthesis
- fungistatic / fungicidal

Question 16

What class of drugs is amorolfine?

Answer 16

Morpholine (amorolfnie is synthetic)

Question 17

MoA of amorolfine and spectrum?

Answer 17

Spectrum mainly dermatophytes and yeast

MOA: inhibits delta 14 reductase and delta 7-8 isomerase so interferes with ergosterol synthesis - usually fungicidal

Question 18

What are echinocandins?

Answer 18

Lipopeptides e.g capsofungin - used IV . OD. Broad spectrum for serious systemic i nfection - candida, aspergillus. NOT for CNS/cryptococcus

Question 19

What are echinocandins NOT used for?

Answer 19

CNS/cryptococcus

Question 20

MoA of echinocandins?

Answer 20

Inhibit production of Beta1-3 glucan (part of cell wall), via . 1-3 Beta glucan synthase
Fungicidal depending on conc

Question 21

What are treatment options for candidasis infections?

Answer 21

Imidazoles e.g. clotrimazole (canesten topical)
Triazoles e.g. fluconazole (canesten oral)
Polyenes e.g nystatin - oral infections, skin, local
Systemic infection–> amphotericin B or capsofungin . (sometimes flucytosine with amphotericin)

Question 22

Treatment for vulvovaginal candidiasis VULVITIS?

Answer 22

Vulvitis - topical imidazole cream - clotrimazole 1% or 2% 2-3 times a day
OR ketoconazole cream 2% 1-2 times a day

Question 23

Treatment for vulvovaginal candidasis - VAGINAL/ vulvovaginal (Main) ?

Answer 23

10% clotrimazole cream 5g insert at night or 500mg single dose pessary at night
OR
can use oral e.g. fluconazole or itraconazole
Fluconazole 150mg single dose
Itraconazole 200mg BD for 1 day

Question 24

What are treatment options for a 12-15 year old girl with vulvovaginal candidiasis?

Answer 24

Use topical clotrimazole 1% or 2% 2-3 times a day. Not oral or intravaginal

Question 25

What are treatment options for pregnant woman with vulvovaginal candidasis?

Answer 25

NOT oral. Intravaginal clotrimazole or miconazole for at least 7 days

Question 26

Common symptoms of vaginal candidiasis?

Answer 26

Pain, itchy, creamy curd like plaques on mucosal surface / discharge.

Question 27

What is nail candidasis and symptoms?

Answer 27

Oncomycosis --> nail abnormal and discoloured, symptoms overlap with those caused by dermatophytes

Question 28

Treatment for oncomycosis?

Answer 28

hygeine, footwear, clip naisl Initially - topical 5% laquer of amorolfine OTC for 6 months on nails, 9-12 months on toes If topical fails or not appt - oral pulsed therapy of itraconazole 200mg BD 1 week (x2 or x3, 21 days apart)

Question 29

what is resistant candida auris?

Answer 29

Fungus similar to c.albicans (thrush) but multi drug resistance e.g. to fluconazole seen in hospitals. Can cause invasive candidiasis and blood steam infection - fungaemia

Question 30

What is aspergillosis infection? how is it . diagnosed?

Answer 30

Aspergillus sp. affects respiratory tract, heart, brain, skin - severe Diagnosed via sputum culture(but . limited value), main ones are bronchoalveolar lavage, antigen detection (NAAT)

Question 31

Treatment for aspergillosis infection?

Answer 31

Voriconazole (triazole) but can also use liposomal amphotericin IV (polyene)

Question 32

What is dermatophytosis?

Answer 32

Filamentous fungi - epidermophyton, microsporum, tricophyton Red scaly patch lesions on skin, nail discolouration/thickening, hair loss and scalp scarring, itchy but rarely painful

Question 33

What location of dermatophytosis is: tinea capitis tinea corporis tinea pedis

Answer 33

Capitis - head scalp Corporus - trunk Pedis - foot -athletes foot

Question 34

Treatment for Tinea capitis?

Answer 34

Systemic griseofulvin or terbinafine + Topical imidazole / selenium sulphide shampoo / imidazole cream

Question 35

Treatment for tina corporis?

Answer 35

Topical imidazole e.g. clotrimazole etc). If not appt or fail - 1st line oral is terbinafine 250mg OD 6 weeks - 3 months for finger and 3-6 months for toes

Question 36

what is pityriasis versicolor?

Answer 36

Skin infection of yeast - malassezia furfur. Brown scaly patches Treatment with azole creams - imidazole - ketoconaozle/ clot for 2-3 weeks.

Question 37

What is histoplasmosis?

Answer 37

Histoplasma capsulatum - inhalation of spores so lung infection. Oral itraconazole. If severe then IV amphotericin B

Question 38

Treatment for cryptococcal infection?

Answer 38

Amphotericin B + Flucytosine IV -- 2 weeks then oral fluconazole for 8 weeks

Question 39

what is aspergillus becoming resistant to?

Answer 39

Azoles

Question 40

Is candida becoming resistant?

Answer 40

Yes