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
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
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
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
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
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
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
9 Pneumocystis jiroveci:
Mold/Yeast/Dimorphic Fungus?
Defining feature
Causes…
Prevention
Mold
Lacks ergosterol
Pneumonia (PJP) in immunocompromised (HIV, organ transplant)
TMP/SMX
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
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
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
9 Important Feature of Other Molds:
Dematiaceous molds
Penicillium marneffei
Fusarium
Scedosporium
Fungal meningitis
Southeast Asia
Hematological malignancies & bone marrow transplantations
Infection in immunocompetent
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
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
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
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
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
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
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
9 Allylamines:
Systemic or Topical Antifungal?
Mechanism
Example(s)
Systemic
Inhibits ergosterol biosynthesis
Terbinafine
- Treats dermatophytes
9 Griseofulvin:
Systemic or Topical Antifungal?
Mechanism
Accumulates in…
Treats…
Systemic
Disrupts mitotic spindle function of growing hyphae
keratinized tissues
Dermatophytoses
9 Nystatin:
Systemic or Topical Antifungal?
Mechanism
Treats…
Topical
Polyene (similar to amphotericin B)
- No systemic absorption
Local Candida infections
9 Clotrimazole, miconazole, & other azoles:
Systemic or Topical Antifungal?
Characteristics
Topical
Too toxic for systemic use, broad spectrum of activity
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LOs: 1-331
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Keywords: 1-826
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LOs: 427
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LOs: 521
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Antibacterials: Summaries33
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Antibacterials27
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LOs: 6-832
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LOs: 923
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Keywords: 9-1426
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LOs: 1024
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LOs: 11-1221
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LOs: 13-1426
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LOs: 15-1628
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Keywords: 15-2921
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LOs: 17-2032
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LOs: 21-2420
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LOs: 25-2719
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LOs: 28-3224
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Keywords: 30-4016
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LOs: 33-3522
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LOs: 36-3821
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LOs: 39-4019
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Micro Summary: Type & Growth94
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Micro Summary: Reservoir/Transmission82
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Micro Summary: Virulence Factors43
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Micro Summary: Diseases90
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Micro Summary: Treatment68
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Micro Summary: Drugs (For, Mechanism, & Side Effects)21
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Micro Summary: Vaccines54
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Micro Summary: Geographical Locations39
