Antifungals

Question 1

How does the -azole group work?

Answer 1

Inhibit C14 alpha demethylase needed for cell membrane ergosterol synthesis by fungi (ie acts in the ER)

Posaconazole kills zygomycetes AND IS SUPERIOR COMPARED WITH FLUCONAZOLE FOR PROPHYLAXIS AGAINST INVASIVE FUNGAL INFECTIONS IN HIGH RISK PATIENTS. Does not kill Sporothrix

Question 2

Voriconazole side effect?

Answer 2

Transient visual disturbance
Asymptomatic hepatic enzymes up
DRUG INTERACTIONS

Good for Aspergillus, candida, scedosporium, fusarium

Question 3

Amphotericin B mechanism? (polyene)

Answer 3

Inserts into cell membrane which increases permeability and all the potassium and intracellular components leak out

Fungicidal
Causes HYPOKALAEMIA

Aspergillus, Candida except lusitaniae
Covers glabrata and krusei
Can treat zygomycosis and fusariosis

Note that Nystatin are polyenes

Question 4

Why do you give lipophilic ambisome?

Answer 4

Less nephrotoxic and greater CNS penetration

Works by liposome preferentially binding fungal cell wall and amphotericin B released to bind ergosterols in the cell membrane forming pores.

Decreases GFR, direct vasoconstriction of afferent arterioles
K, Mg, HCO3 wasting

Question 5

How do echinocandins work?

Answer 5

eg Anidulafungin, Micafungin, Caspofungin (empiric therapy in feb/neut, treat candida infections)

Inhibit glucan synthase which is needed for production of beta 1,3 glucan in fungal cell walls

Cover candida and aspergillosis but not cryptococcus or non-aspergillus moulds

Question 6

Flucytosine mechanism?

Answer 6

Deaminated to 5-FU–>inhibitor of thymidylate synthetase (DNA synthesis)

Work against candida and in combination with Amphotericin for cryptococcus

Question 7

Alemtuzumab incrases rate of which infections?

Answer 7

Ab against CD52
used in CLL or cutaneous T cell lumphoma

Increases mould infections, CMV, PCP

Question 8

What causes PML?

Answer 8

JC virus
natalizumab

Humanised monoclonal antibody against alpha 4 integrin

Question 9

Splenectomy when can you vaccinate?

Answer 9

Vaccinate pre-operatively or 2 weeks post op

Question 10

When can you re-vaccinate following BMT?

Answer 10

6 months post auto

12 months post allo

Question 11

What is the best marker of risk of transmission of HBV after occupational exposure?

Answer 11

HBeAg status of source

Risk actually quite high- 30-50%

Question 12

Allylamines MOA?

Answer 12

eg terbinafine

Inhibit fungal ergosterol synthesis at an earlier stage than the azoles

Question 13

Fluconazole covers…

Answer 13

Most candida except glabrata and krusei (dose dependent)
Could use for candidaemia in non neutropaenic and haemodynamically stable patients

NO mould activity
Does cover cryptococcus so need to give after the 5FC/ambisome finished

Question 14

Itraconazole covers…

Answer 14

Fluconazole + aspergillus + histoplasmosis

Question 15

Voriconazole covers…

Answer 15

Candida including Krusei
Aspergillus
Fusarium (unlike ambisome)
Scedosporium (unlike ambisome)

Question 16

Posaconazole covers…

Answer 16

As vori + zygomycetes
Only oral admin

BETTER THAN fluconazole for prophylaxis in terms of mortality rate

Question 17

Echinocandins cover…

Answer 17

Candida
Aspergillus
NOT cryptococcus
NOT any non aspergillus moulds 
NOT zygomycetes

Used in treatment of IC in neutropaenic patients and in C glabrata infection

Question 18

Candidaemia treatment options…

Answer 18

If immunocompetent, fluconazole, voriconazole, ambisome, capsofungin,

If neutropaenic, capsofungin or liposomal amphotericin B

Question 19

Invasive aspergillosis

Answer 19

Voriconazole first line

Question 20

Zygomycoses

Answer 20

Reverse underlying condition
Debride
High dose amphotericin B

Followed by posaconazole as sequential

Question 21

Which ones get drug level monitoring?

Answer 21

Posiconazole level

Voriconazole level

Question 22

What is galactomannin antigen testing?

Answer 22

A polysaccharide, sometimes comes up in serum before culture of aspergillus in blood.
Can get false positive on Tazocin and false positive from presence of other fungi

HIGH neg predictive value but low positive predictive value