antifungals resistance

Question 1

anti fungal resistance is a common problem with

Answer 1

Flucytosine

Question 2

resistance is rare with

Answer 2

azaleas, polyenes and echinocandins

Question 3

fluconazole

Answer 3

resistance is particularly well recognised

Question 4

fluconazole has primary resistance to

Answer 4

aspergigulus,C.krusei and C. glabrata

Question 5

fluconazole has secondary resistance to

Answer 5

C.alicans and C tropicalis

Question 6

which species has secondary resistance common in HIV associated orphryngeal candidiasis before introduction to anti-retrovirals

Answer 6

C.albicans

Question 7

4 mechanisms of azole resistance

Answer 7

1)reduced intracellular accumulation
2)target site alteration
3_ upregualtion of target enzyme
4) alterations in sterol synthesis

Question 8

reduced intracellular accumulation

Answer 8

• overexpression of energy dependent efflux systems
• effectively pumps azole out of the cell
• resistance linked to over espression

Question 9

target site alteration

Answer 9

point mutation of ERG11- decrease in affinity of azole as a target

Question 10

how many amino acid substitutions are linked to azole resistance

Answer 10

80+

Question 11

up regulation of target enzyme

Answer 11

over expression of ERG11- overcomes competitive inhibitions- leads to modest levels of resistance

Question 12

alterations in sterol synthesis

Answer 12

• growth arrest following azole treatment due to accumulation 14alph-mehy-3,6-diol
• mutation of ERF4 prevents accumulation
• confers resistance to polyenes

Question 13

what mechanism of azole resistance can be conferred to polyenes

Answer 13

alterations in sterol synthesis

Question 14

resistance to flu cytosine (primary)

Answer 14

aspergilla 10% and C.albicans isolate

Question 15

resistance to flu cytosine (secondary)

Answer 15

very common especially following mono therapy e.g. 30% C.albicans isolates develop resistance

Question 16

mechanism of resistance: flucytosine

Answer 16

• loss of permeate activity
• loss of cytosine deaminase activity
• decrease in activity of uracil phosphoribosyl-transferase

Question 17

resistance to Amphotericin (primary)

Answer 17

C.lusitianiae, A.tereus

Question 18

resistance to Amphotericin (secondary)

Answer 18

rare

Question 19

mechanism of resistance in amphotericin

Answer 19

• reduced ergosterol content/ alteration of sterol content
• alteration of sterol/ phospholipid balance
• increased catalase activity

Question 20

increased catalase activity helps confer resistance to amphotericin B because

Answer 20

combats oxidative stress associated with amphotericin exposure

Question 21

resistance to echinocandins (primary)

Answer 21

cryptococcus

Question 22

resistance to echinocanins (secondary)

Answer 22

rare - e.g. 99.6% common candida species isolates are susceptible

Question 23

mechanisms of secondary resistance to echinocandins

Answer 23

• point mutation in B1,3-Glucan synthase

- up regulated chitin synthesis.