MCM 2-41 Pathogenic Fungi

Question 1

what is the main issue with fungi treatment?

Answer 1

we are more similar to fungi than we are to bacteria. there is a lot of “toxic spillover” with antifungal medications that can effect those similar structures in humans

Question 2

hardiness of bacteria vs fungi

Answer 2

fungi can grow in colder, dried, more acidic, and more osmotically hihg pressure areas (high osmotic pressure jelly in the fridge growing mold)

Question 3

two major types of fungi

Answer 3

Yeast - simple single cells, reproduce via budding

mold - more complicated, grow as filaments (hyphae) and form mat (mycelium). growth occurs at tip of filament. asexual and sexual structures

both do mitosis

Question 4

fungi undergo mitosis (TF)

Answer 4

True - however fungi undergo a “closed” mitosis meaning that the nuclear envelope does not disperse - harder to see in microscope

Question 5

sexual or asexual molds are more clinically relevant?

what is important for microscopic diagnosis?

Answer 5

asexual molds

distinct appearance of spores

Question 6

prokaryotes are ___ by definition, fungi are ______

Answer 6

prokaryotes are bacteria

fungi are eukaryotic heterotrophs like humans

Question 7

What must antifungals target? why?

Answer 7

fungi do not have 70s ribosomes or peptidoglycan walls

antifungals must target beta-glucan walls and ergosterol in the membrane

Question 8

TF Antifungals often have some toxicity in humans, and there are many fewer molecular targets available

Answer 8

true - many of their molecules are too similar to ours

Question 9

why are there more cutaneous fungal infections and food spoilage?

Answer 9

fungi can live in the fridge and survive on the hostile enrivonment of the skin because they can can grow in drier, higher-osmotic-pressure, and colder environments than bacteria

Question 10

five types of asexual spores, called ____, have what?

Answer 10

conidia

distinctive microscopic appearances used for diagnosis

Question 11

Thermal dimorphism

Answer 11

: several important fungal pathogens grow as mold at 24C and as yeast at 37C. Yeast form has more immune-evasive properties; dual cultures can be useful for diagnosis.

Question 12

immune response to fungal infection?

Answer 12

granulomatous, sometime also suppurative (pus forming and discharge)

Question 13

most fungal pathoens are…

Answer 13

environmental - little contagion or drug resistance, no eradication
Exception: C. albicans yeast is normal flora / opportunistic pathogen

Question 14

Mycotoxicosis

Answer 14

caused by eating fungal toxins (wrong mushroom or spoiled food); not fungal infection.

Question 15

fungal infection can be diagnosed by

Answer 15

PPD, KOH-mount microscopy with fungal stains, culture on Sabouraud’s agar.

Question 16

major classes of antifungals

Answer 16

are polyenes (disrupt fungal cell membranes at ergosterol insertion sites), azoles (inhibit ergosterol synthesis), echinocandins (inhibit beta-glucan synthesis)

Question 17

polyenes
what do they do?
toxicity?
examples?
treats which fungi?

Answer 17

disrupt cell wall membranes at ergosterol insertion sites

highly effective and broad-spectrum but toxic – Amphotericin B is the only systemic and is nephrotoxic

Question 18

azoles
what do they do?
toxicity?
examples?
treats which fungi?

Answer 18

inhibit ergosterol synthesis

are less toxic; different ones optimally active against different fungi; Fluconazole/Diflucan major one, treats candidiasis and cryptococcosis

Question 19

Echinocandins 
what do they do?
toxicity?
examples?
treats which fungi?

Answer 19

inhibit beta glucan synthesis

are low-toxicity, highly effective against candida and aspergillus

examples end in “-fungin”

Question 20

superficial mycoses

symptoms?
treatment?

Answer 20

caused by fungal grown on superficial skin layer. does not require thermal dimorphism

very common - symptoms are minor; itch or discoloration. treated with topical azoles (fluconazole, diflucan)

fluconAZOLE

Question 21

dermatophytosis

example?

symptoms called?
tranmitted by?
diagnosed with?
treatment?
thermal dimorphism?

Answer 21

example of superficial mycoses

athletes foot - “dermatophytosis” caused by three different fungi genera
infect only superficial keratinized structures via keratinases

symptoms are called tinea

transmitted by fomites or autoinnoculation

diagnose with KOH mount, culture

treat all body sites simultaneously with topical azole

Question 22

subcutaneous mycoses

spread pattern?
thermal dimoprhism?
history of?

treatment

Answer 22

introduced by trauma exposing subcuntenous tissue to soil or vegetation.

slow spread from trauma site towards trunk by lymphatics
-thermal dimorphism

history of ineffective antibiotic treatment

treatment with oral azoles.
serioues cases may require amphotericin B and local surgery

Question 23

sporotrichosis

thermal dimorphism?
transmission?
spreading?

diagnose?

treatments?

Answer 23

example of subcutaneous mycoses
caused by sporothrix spp

thermal dimosphism
enters skin through small injuries like throns/splinters

painless ulcer at site spreads up lymphatics over years

if immunocompromised - may be dissemintated meningitis

diagnose biospy and culture at room temp from pus (turn it from yeast form to mold form)

treat normal type with oral azoles
more serious forms with amphotericin B

Question 24

Systemic Mycoses

tramission?
thermal dimosphism?
severity?
problem?

Answer 24

these are environmental spores/fungi in soil that get inhaled into the lungs. not person to person

thermal dimorphism

range of severity - asymptomatic to death

may mimic TB, but source is american dirt not foriegn crowds

Question 25

Histoplasma

thermal dimorphism?

endemic areas?

transmission?

symptoms?

diagnosis?

treatment?

Answer 25

example of a systemic mycoses

thermally dimorphic with mold/yeast forms

endemic to ohio, missouri, mississippi

soil based infectious microconidia (micro spores) kicked up

causes pulmonary symtpoms
previously healthy - clear or granulomas
higher dose - TB mimic
CMI deficient host disseminates in macrophages (yeast survive lysosomal fusion by producing ammonia). look for pancytopenia and tongue ulcerations

diagnosis - history is critical, biopsy for yeast in macrophages, cultures for dimorphism, ELISA for antigen

treat serious lung w/ itraconazole, meningitis with fluconazole, disseminated with amphotercin B

Question 26

Opportunistic mycoses

Answer 26

diseases/severity widely varied, depends on pre-exisitng conditions.

optimal treatment addresses infection an the underlying problem

Question 27

cryptococcosis

typical patient?

symptoms?

treatment?

Answer 27

environmental
enabled by reduced CMI, suppresses host inflammatory response

presents late in disease with meningitis and skin nodueles or pulmonary symtpoms

diagnose by CSF or “CRAG”

treat in combo with of flucytosine and Amphotericin B initially, then long-term fluconazole.

Question 28

histoplasma of immunocompromised vs immunocompetent

Answer 28

previously-healthy usually clear or contain in granulomas, higher-dose infection produces TB mimic, CMI-deficient host disseminates in macrophages (yeast survive lysosomal fusion), look for pancytopenia and ulcerations on tongue.

Question 29

how do histoplasma disseminate?

Answer 29

enter phages, survive lysosomal fusion, spread to sites in body

Question 30

main diagnostic for cryptococcosis?

Answer 30

Oval - big thick capsule (KEY). Important virulence factor (hard for phags to engluf) and good for diagnostic.

Question 31

polyenes

Answer 31

Disrupt cell membranes at ergosterol insertion sites. Highly effective and broad-spectrum, but toxic. Amphotericin B is the only systemic polyene, and it is nephrotoxic.

Question 32

Azoles

Answer 32

Inhibit ergosterol synthesis. Less toxic than polyenes. Different drugs within the class are optimally effective against different fungi. Fluconazole is the major azole drug; it treats candidiasis and cryptococcosis.

Question 33

• Echinocandins

Answer 33

Inhibit beta-glucan synthesis. They have low toxicity and are highly effective against Candida and Aspergillus.

Question 34

amphotericin B

Answer 34

The most lifesaving antifungal drug is amphotericin B. It is a systemic (administered via IV) polyene antifungal. It is non-teratogenic, making it the drug of choice for treating systemic mycosis in pregnancy.

Question 35

Flucytosine

Answer 35

an antifungal that is used in conjunction with another antifungal (often amphotericin B). When converted into one of its active form in fungal cells, it can either inhibit fungal DNA synthesis or inhibit certain crucial protein syntheses. It has lower efficacy and a faster development of resistance than other antifungals, hence why it is used in conjunction with other antifungals. It is also toxic to many body systems, and is not particularly safe to use during pregnancy.

Question 36

most life saving antifungal

Answer 36

amphoterin B

Question 37

Nyastatin

Answer 37

Nystatin is other important poly-ene - too toxic for systemic, good as topical

Question 38

most fungal pathogens are _______ except for _______

Answer 38

environmental

c.albicans, yeast is normal flora/opportunistic pathogen

Question 39

how to treat systemic mycosis in pregnancy.?

Answer 39

amphoterin -B is no tetratogenic. making it the drug of choice for treating systemic mycosis in pregnancy.