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Flashcards in LOs: 9 Deck (23):
1

9 Fungi vs. Bacteria

Cells

Nuclear membrane, mitochondria, ER, & sterols?

# Chromosomes

Ribosome

Cell wall made of...

Heterotrophic?

O2 cells

Dimorphism?

F: eukaryotes
B: prokaryotes

F: yes
B: no

F: >1
B: 1

F: 80S
B: 70S

F: glucans, mannoproteins (mannas), chitin, chitosan
B: murein, teichoic acids (gram+), peptidoglycans

F & B: yes

F: obligate or facultative aerobes (no photosynthesis)
B: obligate aerobes & anaerobes, facultative anaerobes

F: yes
B: no

2

9 Growth forms of fungi:
Molds

AKA

Unicellular/Multicellular?

Basic element

Speciated by

Filamentous fungi

Multicellular

Hyphae
- Branched, tubular
- Grow by branching & longitudinal extension
- Septate: divide hyphae into discrete units
- Non-septate: single continuous cell
- Mycelium: web of intertwined hyphae

Morphology, color, & microscopic appearance

3

9 Growth forms of fungi:
Yeasts

Unicellular/Multicellular?

Shape

Reproduction

Produce...

Speciated by

Unicellular

Round to oval, form smooth flat colonies

Reproduce by budding

Pseudohyphae: buds that fail to detach & become elongated yeast cells chained together that resemble true hyphae

Biochemical tests

4

9 Growth forms of fungi:
Dimorphic fungi

Grow either as molds or yeasts depending on environmental conditions

Molds (hyphae): saprophytic stage

Yeasts (budding): parasitic stage

5

9 Candida:

Mold/Yeast/Dimorphic Fungus?

Most common mycoses

Most common infectious species

Inhabits...

Risk factors for disease

Cutaneous & mucosal diseases & treatment

Systemic diseases & treatment

Yeast

Candidiasis

Candida albicans

Mouth, skin, GI tract, & vagina

Conditions that alter:
- Normal bacterial flora (antibiotics)
- Cellular immunity (steroids, anti-metabolites)
- Granulocytes
- Mucosal membranes (chemotherapeutic agents)
- Spillage from GI tract (GI surgery)

Thrush, esophagus infections, & vulvovaginitis (moist, warm parts of body)
- Nystatin, azoles

Bloodstream infections
- azoles, echinocandins, amphotericin B

6

9 Cryptococcus neoformans:

Mold/Yeast/Dimorphic Fungus?

Common species & their locations

Pathogenesis

Manifestations

Diagnosis (3)

Treatment

Yeast

C. neoformans (worldwide) & C. gattii (tropical areas)

Polysaccharide capsule (defense against phagocytoses) & melanin (defense against oxidative stress)

- Most pts w/ cryptococcosis are immunocompromised
- Fungus enters body via respiratory tract, spread hematogenously to CNS, & causes meningitis, meningoencephalitis, or bloodstream infections

India Ink of CSF, serologic detection of cryptococcal polysaccharide antigens, or culture

Amphotericin + 5-flucytosine followed by fluconazole

7

9 Dermatophytes:

Mold/Yeast/Dimorphic Fungus?

Infects...

Location

Sources of infection (3)

Diagnosis

Treatment (topical & oral)

Mold

Superficial keratin layer of skin (using keratin as nutritional source)

Tropical areas

(1) Zoophilic (animal)
- Microsporum canis --> tinea corporis ("ring worm")
(2) Geophilic (soil)
(3) Antrhopophilic (humans)
- Trichophyton rubrum --> tinea pedis ("athlete's foot") & tinea cruris ("jock itch")
- Onychomycosis (nail infection)

Microscopic examination & culture of skin/nail scrapings/clippings

Topical: imidazoles
Oral: terbinafine, azoles

8

9 Pneumocystis jiroveci:

Mold/Yeast/Dimorphic Fungus?

Defining feature

Causes...

Prevention

Mold

Lacks ergosterol

Pneumonia (PJP) in immunocompromised (HIV, organ transplant)

TMP/SMX

9

9 Aspergillus:

Mold/Yeast/Dimorphic Fungus?

Most common species

Manifestations (7)

Pathogenesis

Diagnosis

Treatment

Mold

A. fumigatus (most significant & severe), A. niger (rare)

Respiratory tract
- Airway colonization
- Allergic bronchopulmonary aspergillosis (ABPA)
- Tracheobronchitis
- Sinusitis
- Aspergilloma ("fungus ball")
- Invasive pulmonary aspergillosis
- Disseminated aspergillosis

- Inhalation of spores
- Evasion of pulmonary macrophages or neutrophils
- Local lung infection
- Entry into blood vessels
- Dissemination

Branching septate hyphae, culture, or galactomannan antigen in blood & bronchoalveolar lavage fluid

Amphotericin, Voriconazole, Posaconazole, Itraconazole, Echinocandins, but NOT Fluconazole

10

9 Mucor, Absidia, Rhizopus, Rhizomucor (Zygomycoses):

Mold/Yeast/Dimorphic Fungus?

Cause infections in pts w/...

High affinity for...

Most common disease

Therapy

Mold

Immune deficiencies, metabolic disorders (diabetes), & free iron rich states

Vascular structures

Rhinocerebral (mucormycosis)

Amphotericin B, surgical resection, Posaconazole

11

9 Sporotrichosis:

Mold/Yeast/Dimorphic Fungus?

Causative species

Disease

Occur in pts w/...

Common presnetation

Mold

Sporothrix schenckii (thermally dimorphic, lives on vegetation)

Cutaneous disease resulting from inoculation of fungus on skin

Exposure to soil or infected plants (ex. rose gardeners)

Non-healing, inflamed nodule that doesn’t respond to
antibacterials, lymphatic spread

12

9 Important Feature of Other Molds:

Dematiaceous molds

Penicillium marneffei

Fusarium

Scedosporium

Fungal meningitis

Southeast Asia

Hematological malignancies & bone marrow transplantations

Infection in immunocompetent

13

9 Histoplasma capsulatum:

Mold/Yeast/Dimorphic Fungus?

Location

Acquired via...

Clinical presentation

Detection

Therapy

Dimorphic Fungus

Ohio & Mississippi River valleys (soil)

Respiratory tract (bird droppings & bat guano promote growth of organism --> caves & bird roosts)

- Acute primary infection (asymptomatic or mild flu-like)
- Mediastinal granuloma & fibrosis
- Chronic pulmonary histoplasmosis or cavitary pulmonary histoplasmosis
- Disseminated histoplasmosis

Antigen in urine & serum

Amphotericin, itraconazole

14

9 Coccidioides immitis:

Mold/Yeast/Dimorphic Fungus?

Causative species

Causes...

Location

Associations

Dimorphic Fungus

C. immitis, C. posadasii

Coccidiomycosis ("valley fever")

Southwest US

- Peripheral eosinophilia
- Erythema nodosum
- Dissemination to CNS, bones ,joints, & skin

15

9 Blastomyces dermatitidis:

Mold/Yeast/Dimorphic Fungus?

Location

Causes...

Frequency

Dimorphic Fungus

Ohio & Mississippi River valleys

Blastomycosis (chornic, granulomatous & suppurative lesions in lungs, dissemination to skin & bones)

Less common than histoplasmosis

16

9 Polyenes:

Systemic or Topical Antifungal?

Mechanism

Example(s)

Systemic

Binds to sterols in membrane, increases permeability

Amphotericin B
- Fungicidal
- Active against almost all fungi
- Side effects: nephrotoxicity, infusion-related, hypokalemia, hypomagnesemia

17

9 Azoles:

Systemic or Topical Antifungal?

Mechanism

Characteristics

Example(s)

Systemic

Disrupts ergosterol biosynthesis

- Fungiastatic
- Well tolerated except liver toxicity

Ketoconazole, Fluconazole, Itraconazole, Voriconazole, Posaconazole
- Imidazoles: topical, for cutaneous infections

18

9 Echinocandins:

Systemic or Topical Antifungal?

Mechanism

Active against...

Not active against...

Tolerability

Example(s)

Systemic

Inhibits 1,3-beta-D-glucan synthesis in cell wall

Candida & Aspergillus (serious)

Cryptococcus & Zygomycetes

Well tolerated except histamine-like reactions & liver metabolism

Caspofungin, Micafungin, Anidulafungin

19

9 Antimetabolites:

Systemic or Topical Antifungal?

Mechanism

Example(s)

Systemic

Interferes w/ DNA synthesis

5-flucytosine
- Combination therapy w/ amphotericin to treat cryptococcosis or candidiasis
- Monotherapy induces resistance

20

9 Allylamines:

Systemic or Topical Antifungal?

Mechanism

Example(s)

Systemic

Inhibits ergosterol biosynthesis

Terbinafine
- Treats dermatophytes

21

9 Griseofulvin:

Systemic or Topical Antifungal?

Mechanism

Accumulates in...

Treats...

Systemic

Disrupts mitotic spindle function of growing hyphae

keratinized tissues

Dermatophytoses

22

9 Nystatin:

Systemic or Topical Antifungal?

Mechanism

Treats...

Topical

Polyene (similar to amphotericin B)
- No systemic absorption

Local Candida infections

23

9 Clotrimazole, miconazole, & other azoles:

Systemic or Topical Antifungal?

Characteristics

Topical

Too toxic for systemic use, broad spectrum of activity