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Flashcards in chronic necrotizing pneumonia: fungal Deck (110):
1

fungi characteristics

more "human-like" (EUK) so tx is v. toxic (amphoteracin B)
heterotrophs, absorb nutrients, parasitic
obligate aerobes, EXCEPT YEAST: facult. anaerobe
cell wall: polysacchs(glucan, chitin) and glycoproteins
cell mem: ergosterol, other sterols (site of drug axn)
some encapsulated: cryptococcus neoformans

2

fungi disting. based on

morphology of spores and hyphal elements
(bac: stain, cell/colony morph., biochem rxns)

3

2 basic fungi growth forms

molds/mycelial (saprobic) growth:
spores germ.-->hyphae (branching or unbranched filaments) +/- septa, (hyphal mass: mycelial)
sexual and asexual spores

yeast OR spherules w. endospores

4

yeast

round-oval elongated *single cell*
reprod. by budding, form moist or mucoid colonies (resem. G+ cocci)

5

pseudohyphae (yeast)

buds remain attached to mom (candida), elongate, lack parallel sides and pinching septa

6

true hyphae

parallel sides, true horiz. septa, can prod. terminal, thick walled chlamydoconidia

7

candida albicans (not other spp.) produces a

germ tube in human serum @ 37 degrees C
ddx for c. albicans

8

yeast cells can convert

into hyphe/pseudohyphae and back again, *dimorphic, but not thermally dimorphic*

9

thermally dimorphic fungi

yeast OR spherules/endospores (parasitic) in host/in vitro @ 37 C

mold (saprobic) in environ. @ 21-24 C

10

therm. dimorph fungi orgs

histoplasma capsulatum
blastomyces dermatitidis
coccidioides immitis, c. posadasii
sporothrix schenckii

11

molds can produce spores called..

conidia: "naked" spores, unenclosed
macroconidia: large, CANNOT cause RT disease
microconidia: small, can get into alveoli, *can cause RT inf.* (21-24 C: environ./in vitro)

12

microconidia-prod. spp.

histoplasma capsulatum
blastomyces dermatitidis
aspergillus spp.
murcormycoses

13

arthroconidia (arthrospores)

(mold-produced)
thick-walled, fragments of hyphal cells
*can cause RT inf.*
coccidioides immitis and c. posadasii in environ/in vitro @ 21-24 C

14

sporangiospores

spores w. in sac-like structures (sporangia)

15

sporangia prod. spp

coccidiodes immitis and c. posadasii: spherules**
PCP (pneumocystis jiroveci)-cysts w. endospores (8)

16

c. immitis and c. posadasii produce sporangiospores...

spherules (sporangia) bearing endospores (sporangiospores)
**spherules is pathognomonic for coccidioidomycoses**
-rupture-->rel. endospores, can dev. into spherule
*neither is infectious*

17

yeast produce spores called

blastospores: buds

18

systemic mycoses (mycoses=fungal infections)

most serious, break down int. orgs, viscera (enter via RT, skin break)
orgs:
blastomyces dermatitidis
coccidioides immitis and c. posadasii
histoplasma capsulatum
cryptococcus neoformans var. grubii (CNS)

19

opportunistic mycoses

human NF or environ. orgs, cause lesions on mucus mem. or in skin, RT, CNS
(@ risk: br-sp abx tx, IC)
orgs:
aspergillus
cryptococcus neoformans var. grubii
**candida spp.**most important
zygomycetes class: absidia, mucor, rhizomucor, rhizopus (mucormycosis)

20

fungal pneumo CANNOT be dx by

routine sputum Cx
s/s (no unique)
*does NOT respond to antibiotics
-pay attn to hx, PE, epidemiology

21

host immune system determines fungal pathogen infections, esp.

T cell deficiencies
phagocytic cells (PMNs, macros)

22

T cell opportunistic fungi

histoplasma capsulatum
blastomyces dermatitidis
coccidioides immitis and posadasii
cryptococcus neoformans
candida albicans and other spa.
pneumocystis jiroveci

23

what is required to control fungal inf. and/or disease

CMI: non-immune ppl can be infected, also those w. imp. T cell function: HIV+, glucocorticosteroid/immsupp tx (SOT)

24

phagocytic cell opportunists

aspergillus
zygomycetes class (mucormycosis)
@ risk:
prol. neutropenia (depressed PMNs

25

normal functioning phago cells

macros destry conidia
PMS destroy hyphae

26

causes of iron overload

kidney dialysis
unreg. DM: DKA inhib. iron bind to transferrin: elev. Fe in serum
hemochromatosis

27

the systemic mycoses (histoplasma apsulatum, blastomyces dermatitidis, coccidioides immitis and posadasii)

primarily pulm. pathogens
most common syst. fungal inf. in immunocompetent and immunocompromised hosts in NA
eukaryotic, thermally dimorphic

28

H. capsulatum and B. dermatitis produce this in soil (25 C) that are infectious to humans

microconidia (spores)-->yeast in humans: parasitic form (37 C)

29

C. immitis and C. posadasii produce this in soil (25 C) that are infectious to humans

arthrospores (resistant, barrel-shaped)-->spherule and endospores: parasitic form (37C)

30

systemic mycoses: transmitted person to person?

NO, via inhalation of aerosolized microconidia/arthrospores (not via resp. droplets)
(target is LRT)

31

histoplasma capsulatum (histoplasmosis, Darling's disease, spelunker's)

Ohio-Miss. river valley, guano

32

blastomyces dermatitidis (blastomycosis, Chicago disease)

soil near lakes, rivers of Missouri, Arkansas, St. Lawrence, overlaps w. histo but larger

33

coccidoides immitis and c. posadasii (coccidioidomycosis, desert rheumatism, valley fever, san joaquin valley fever)

American SW, Latin America
C. immitis: San Joaquin Valley

34

syst. mycoses patho

sev. immsuppr pts @ risk
*asymptomatic more common
-micro/arthr are phago by non-act. macros
*only histo grows IC
-->all may dissem. via blood-->extrapulm. inf.

35

syst. mycoses patho: host response to inf

sp. CD4+ T cells required for control of inf., need activated macros (transplant, HIV pts @ risk)
effective CMI forms tubercle-like lesion where repo. happens-->calcify
incubation period: 1-3 wks

36

syst. mycoses s/s (sev. options)

1. flu-like/bronchitis: fever, malaise, dry, non prod. cough
2. flu-like w. anything from atypical pneumo-->chronic granulomatous disease in lungs (indist. from pulmonary tb) and cavitary lesions (+/- night sweats, anorexia/W.L., dry non prod. cough or prod. +/- hemoptysis, CP (p/np), SOB, dyspnea
3. *progressive dissem./systemic disease*: EITHER
-gen. systemic inf/dis
-extrapulm. inf. of sp. orgs. or tissues +/- pulm. involvement (each organ has sp. targets)

37

progressive disseminated targets of histoplasmosis

liver, spleen, adrenals

38

progressive disseminated targets of blastomycosis

skin, soft tissue, bone (osteolytic), GU tract

39

progressive disseminated targets of coccidioidomycosis

skin, soft tissue (rashes), bones (osteolytic, skel. pain), joint/synovium, CNS (meningitis)

40

systemic mycosal infections CXR

heal by fibrosis-->necrotic "coin-like" lesions (like TB/neoplasm) *esp. histoplasmosis

41

systemic mycosis s/s in sev. immsuppr. pts

fever, w.l., night sweats, pulm. sympts (cough, dyspnea), anemia in many pts, loc. or gen. lymphadenopathy, hepatosplenomegaly, skin/colon ulcers

42

syst. mycoses dx: stain/Cx

KOH-sample stain shows parasitic form (yeast or spherule)
Cx: variable growth, alert lab (esp. C. immitis, C. posadasii- dangerous!)
DNA probs/exoantigen tests

43

syst. mycoses dx: serology?

Yes, for b, h, c

44

syst. mycoses dx: DTH skin testing

histoplasmin (mycelial Ag) : epi studies of histoplasmosis
spheruline: dx/px of coccidioidomycosis

45

syst. mycoses CXR:

variable;
coin-like lesions/nodular masses
diffuse bilateral alveolar infiltrates
consolidation
combos of above

46

syst. mycoses tx

Amphotericin B lipid formulation- may be prolonged

47

histoplasma capsulatum epi

wood w/ bird poop

48

histo cap patho

asymptomatic, may observed calcified tubercle-like lesions on XR: liver, spleen, adrenals, lungs

49

histo cap: progressive disseminated disease (Darling's)

in adults: like military TB; lesions in liver, spleen, adrenals-->may result in Addison's
in infant: persist. fever, hepatosplenomegaly, death in 6 wks if unto
*charac. by massive parasitism of macros*

50

histo cap dx:

like TB (infiltr/consol. on XR)
rounded-oval yeast forms in macros

51

histo cap dx: serology

-complement fixation (mycelial Ag and whole yeast cell Ags (histolyn)
-immunodiffusion test:
H Ag+: active histo, primary dis.
M Ag+: acute or chronic dis.
-RIA (polysac. Ag in urine/serum), ELISA (Ab to histo Ag 69-70kDa in serum)

52

histo cap tx

Amphotericin B, oral itraconazole after

53

blastomyces dermatitidis epi

also dis. in dogs

54

blasto derm patho

chronic necr. pneumo + coin-like lesions
extrapulm manifests:
*skin lesions-like SCC*
bone lesions
GU- less common, prostate, epidid.

55

blasto derm dx:

*BROAD-BASED, budding yeast form w/ v. THICK WALLS*
-ELISA (screen), immunodiffustion (confirm)

56

blasto derm tx:

Amphotericin B, oral itraconazol after

57

coccidioides immitis and posadasii virulence factor

estrogen-binding proteins (progesterone, testosterone, 17B-estradiol)
inc. steroid hormone levels-->stim. growth and maturation of spherules

58

c. immi and posa epi

SW US (immitis), Latin America
rains-germinate in soil-mycelia grow-form arthroconidia-dust stirred up-epidemics
*dissem: males, preggos (3rd trimester), immsuppr, minorities?
*SUMMER!*

59

c. immi and posa patho

60% asymptomatic, (DTH test + to spherulin)
40% inf.: symptomatic 2 wks (10-16d)

60

c. immin and posa s/s

see earlier for gen. manifest.
cutaneous: macpap rash (esp. kiddos), erythema nodosum/multiform (white women, good px)
-traids
most self-limiting, not all, dissemination is rare (0.5%) but insidious and fulminant

61

desert rheumatism: 2 triads
(c. immi and posa)

fever, erythema nodosom, arthralgias
conjunctivitis, erythema nodosum, arthralgias

62

c. immi and posa pathognomonic dx

*spherules: 5-40 um and/or endospores in tissue*

63

c. immi and posa serology dx

IgM: + 1st mo, neg by 2 mos (prim. inf)
IgG titers: +2-3 wks-8mos, dx and px (high-disseminated, drop w/ succ. tx)

64

c. immi/posa most likely if

+ spherulin rxn (w.in 3 wks, good px)
s/s consistent
resident/travel to endemic area (SW, LA)
(w. disseminated, may be DTH -: high relapse rates, converts to + w/ succ. tx)

65

c. immi/posa tx

amphotericin B, then oral itraconazol

66

aspergillosis and mucormycosis/zygomycetes epi

both: ubiquitous distribution (geography), POE is RT (inhalation of microconidia)
(inhale sev. 100 A. fumigatus conidia/day)

67

asperg. patho

allergic bronchopulm. aspergillosis (ABPA): in bronchial asthmatic pt
aspergilloma ("fungus ball") lung parenchymal displacing mass
invasive aspergillosis (IA)

68

asperg and mucor dx (both)

clin. features depend on organ, XR, Cx/microscopic evidence

69

asperg dx

resence of aspergillus galactomannan (GM) in BAL specimen or serum
halo sign by lung CT scan

70

asperg and mucor tx

voriconazole (broad-spec triazole) followed by amphotericin B

71

asperg and mucor ppx

posaconazole (not fluconazole, itraconazole)

72

aspergillosis: dimorphic fungus?

no

73

aspergillosis spp.

a. fumigatus (most common), a. flavus, a. niger

74

asperg cell morph

non-pigmented, harry septate hyphae ("soldiers marching in a row"), acute angle branching (45-90 degrees)

75

asperg epi

ubiquitous geo, POE RT, inhale lots a. fumigatus conidia/day

76

asperg risk factors

(gen ones) +
lung structural abnormalities
over-exuberant IR (hypersens, atopy?) in allergic asperg.
severely immcompromised

77

asperg: syndromes involving mycelia growth in body, req. tx

ABPA: allergic bronchopulmonary aspergillosis
aspergilloma
IA: invasive aspergillosis

78

ABPA

most sev. allergic pulm comp caused by aspergillus spp.
in some pts w. atopic asthma (1-2%) or CF (7-35%)
*immunopathology* hurts host more than fungal growth

79

ABPA clin manifests

worsening bronch. asthma (brown mucus plugs in prod. cough + wheezing), transient pulm. infilt.--> fatal lung destruction

80

ABPA: Loeffler's syndrome

fever, cough, *urticaria, wheezing, inter. infilt. on CXR, *sputum + eosinophilia (>500/mm3) + Charcot-Leyden crystals (deg. eosinophil granules), peripheral eosino. w. CBC*

81

ABPA: 5 major definitive dx

asthma hx
immediate (15mm+/-5mm) skin reactivity to A. fumigatus Ag extract
elevated serum levels IgM, IgG, IgE against A. fumigates
elevated total IgE serum levels (>1 ug/mL)
central (proximal) bronchiectasis

82

aspergilloma

"fungus ball" of fungal hyphae
-displaces lung parenchyma
-in 10-15% of cavities from lung dis (TB, sarcoid)
-chronically obstr. paranasal sinuses

83

aspergilloma patho

-spheroid mass of hyphae in proteinaceous matrix w. sporulating structures @ periphery
-balls external to cavity lining (i.e. airway)
-as hyphae grow, rel. enzymes-->destroy human tissue and break down macromol (protein, aas)-->disrupt BVs in cavity wall/bronchial supply-->1 or both: massive internal bleeding +/- hemoptysis (bleed in airway) (either can be fatal)

84

aspergilloma symps

hemoptysis, bronchiectases in late disease

85

aspergilloma dx

CATscan: spherical mass surrounded by radioluscent crescent
bronchioscope: fungal ball

86

invasive aspergillosis (IA)

acute or chronic pulmonary IA* most
-other: tracheobronchitis, obstructive dis. (AIDS), acute/chronic invasive rhinosinusitis
-dissem. sites: brain, skin, eyes

87

IA risk factors

*leading COD among*:
blood Ca: lymphoma, leukemia pts
sev. neutrophenic pts
tx w. cytotoxin for blood dis
BM transplant, SOT
kiddos w. chronic granulomatous disease
AIDS pts

88

IA patho

growth of fungus in lung tissue-->hemorrh. infection-->dissem via blood-->fungal hyphae grow in tissue (not ball in cavity)
(histo reveals 1/few short segments of larger hyphal elements)

89

IA presentation in neutropenic pt

persistant fever, fails to respond to br. spec abx
+/- cough, min sputum prod.
hemoptysis is uncommon

90

aspergillosis dx: imaging

(depends on organ location)
+ CT scan: large nodules w. "halo sign" (hazy, nonobstruc. ground glass attenuation)
-->invasion of vascu.-->hemorrhage (1st 10d), early sign
-air crescent sign-->later (IA), invasion-necrosis, host mounts an inflammatory resp

91

aspergillosis dx: Cx

narrow, septate hyphae w. acute angle (45-90) branching, in tissue

92

aspergillosis dx: serum

aspergillus galactomannan (GM) in BAL spec./serum, (not for SOTs) -detectable 5-8 days before s/s, correlates to fungal tissue burden, serial assays 2x/week + CT/Cx
-also: LAtest for GM, ELISA (using MAb sp. for 1-5-B-D-galactofuranose) side chains of GM

93

aspergillosis tx

voriconazol (b-spec triazole) then amphotericin B
**survival rates POOR** (>80% mortality w. CMI suppression)
ppx: posaconazole

94

mucormycosis/zygomycosis: dimorphic?

NO

95

mucormycosis/zygomycosis orgs

absidia, mucor, rhizomucor, rhizopus

96

mucor cell morph

variable width (6-25 um), broad, ribbon-like
thin walled
infreq. septat or aseptate hyphae
irregular branching (includes wide angle 90)

97

mucor patho

typ: progressive and fatal w.in 2-3 wks
risks: abn. +/- LOW #s PMNs
infection from inhale. of spores into bronchioles and alveoli leading to prim. infarc/necrosis w. cavitation-->blood dissem to other orgs (brain)

98

mucor manifests

persistant fever, rap. prog. pneumo w. hemoptysis, pleuritic CP

99

mucor dx

need to make early!
ID ribbon-like, aseptate hyphae in tissue and Cx
*microscopy is most rapid dx*
"prominent infacrcts, angioinvasion and perineural invasion*: both aspergillus and mucormycoses
**Dx typically made on autopsy**

100

mucor tx

voriconazole then amphotericin B
no ppx

101

5-fluorocytosine (5-Fc)

nucleoside analog
interferes w. DNA and RNA syn/func

102

griseofulvin

mitosis inhibitor
inhibition of fungal cell mitosis at metaphase by interaction w. polymerized microtubules

103

echinocaandins, pneumocandins, caspofungin

inhib. cell wall syn. by inhib. syn. of 1,3-B-D-glucan in fungal cell walls

104

amphotericin B-lipid formulations

polyene antibiotics
interaction w. ergosterol, formation of aqueous channels, inc. mem. perm to univalent cations and -->cell death

105

ketoconazole

imidazole/azole
causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

106

flucanozole

imidazole/azole
causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

107

itraconazole

imidazole/azole
causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

108

voriconazole

imidazole/azole
causes ergosterol depletion and accum. of aberrant and toxic sterols in cell mem

109

amorolfine

morpholine
inhib. sterol reductase and isomerase

110

terbinafine

allylamines/thiocarbamates
causes ergosterol depletion and accum. of aberrant and toxic sterols in the mem

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