• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/56

Click to flip

56 Cards in this Set

  • Front
  • Back
Fungi
Eukaryotic organisms with nucleus, nuclear membrane, ER, & mitochondria
~80,000 species of which <400 (<0.5%) are medically important
<50 species cause >90% of human infections
Invasive fungal infections
(deep fungal infections or deep mycoses)→Infections that involve internal organs (skin +/- involved)
Filamentous fungi (moulds)
Grow as multinucleate, branching hyphae, forming a mycelium; undergo asexual reproduction
Yeast
Grow as ovoid or spherical single cells that multiply by budding & division
Dimorphic fungi
Form hyphae at environmental temperatures (25 degrees C) but grow as yeast in the body (37 degrees C)
I.e. Blastomyces, coccidiodes, histoplasma
Invasive Fungal Infections Epidemiology
Many of the fungi that cause human disease are free-living organisms in the environment (e.g. Aspergillus) that may be acquired by inhalation, ingestion, or inoculation thru the skin; certain of these fungi have a very restricted geographic endemicity (e.g. Coccidioides)→Exogenous in origin
Some fungal pathogens are part of the normal human flora (e.g. Candida) & invade when host defenses become impaired→Endogenous in origin
Human to human transmission is uncommon
Invasive Fungal Infections Incidence
Population of pts at risk for IFIs has expanded dramatically over past 20 yrs
-Aggressive chemoRx of malignancies
-Increasing #’s of transplants
-Expanding usage of immunosuppressive Rxs
-HIV epidemic
-Increasing encroachment of humans into sylvan habitats
As a consequence, incidence of, & mortality due to, IFIs has significantly ↑’ed
IFIs: Endemic Mycoses
Blastomycosis
Histoplasmosis
Coccidioidomycosis
Sporotrichosis
Paracoccidioidomycosis
Invasive Fungal Infections
Diagnosis
Epidemiology
Clinical features
Radiographic findings
Histopathology
-Potassium hydroxide (KOH)
-Gomori methenamine silver (GMS)
-Periodic acid-Schiff (PAS)
Culture
-Sabouraud’s agar
-Brain heart infusion agar
Serology or antigen detection
Blastomycosis
Clinical Features
Majority of infected pts manifest symptomatic clinical disease (≥ 90%)
Causes an acute or chronic pneumonia
May disseminate to skin, bone, GU tract, or liver
Mimics malignancy (esp. lung and skin)
Blastomycosis
Epidemiology
Endemic to southeastern/south central US, the Great Lakes region, & near St. Lawrence River
Acquired via inhalation during outdoor activities near decaying vegetation, moist soil, or body of water
Blastomycosis
Diagnosis
Smears & histopath
-Broad-based budding yeasts with thick refractile walls (KOH, GMS, PAS)
Culture
-Sabouraud dextrose agar→Grow as a mould
Serology
-Not reliable
Antigen detection
-Emerging utility as diagnostic test; serum & urine
Blastomycosis
Treatment
Severe disease
Amphotericin B
Blastomycosis
Treatment
Mild to moderate disease
Itraconazole (fluconazole)
Blastomycosis
Key Teaching Points
Dimorphic fungus
SE & south central US & Great Lakes area
<10% asymptomatic : >90% symptomatic
Chronic pneumonia; skin
Broad-based budding yeast
No useful serology (? serum antigen)
Amphotericin or itraconazole
Histoplasmosis
Epidemiology
Endemic to Ohio & Mississippi River valleys, Mexico, & Central America
Acquired via inhalation of conidia during dust storms or building renovation or near large quantities of bird or bat guano in caves
Histoplasmosis
Clinical Features
Majority of infections asymptomatic; 10% of patients have clinical disease
Chronic pneumonia; mucosal ulcers
Disseminated infection +/- CNS involvement in the compromised host
Which fungi grows readily in bird/bat droppings?
Histoplasmosis
Histoplasmosis
Diagnosis
Smears & histopath→Ovoid 3-5 µm yeasts with narrow-based budding; often within macrophages; seen best with GMS
Culture→Sab; grows as mould
Serology→Comp fix
Antigen detection→Mainstay of dx; urine > blood; sensitivity 75+%
Skin testing→Useful for epi not clinincal dx
Histoplasmosis
Treatment
Majority of pts require no Rx (remember it is asymptomatic)
Severe disease
Amphotericin B
Mild to moderate disease
Itraconazole or fluconazole
Histoplasmosis
Key Teaching Points
Dimorphic fungus
Mississippi & Ohio River valleys
90+% asymptomatic : <10% symptomatic
Pneumonia; disseminated infection
Small yeast often within macrophages
Serum and urine antigen assays
Amphotericin or itraconazole
Coccidioidomycosis
Epidemiology
Endemic to southwestern US (epicenter in south central Arizona), Mexico, & S. America→Travel hx
Inhalation of arthrospores when arid, sandy desert soil is disturbed→Military maneuvers in the desert; archaeological digs; off-road riding, etc
Coccidioidomycosis
Clinical Features
60% of infxns asymptomatic
Acute or chronic pneumonia
Disseminated disease→Skin, bones and joints, CNS
Erythema nodosum
Coccidioidomycosis
Diagnosis
Smears & histopath→Spherules & endospores
Culture→Grows on routine media as well as Sab→Mould
Serology→Comp fix useful in predicting dissemination (1:16)
Antigen detection→Under developement
Skin testing→Useful as epidemiologic tool
Coccidioidomycosis
Treatment
“Uncomplicated” pneumonia
-“Watchful waiting” (predictors of progression) or itraconazole
Progressive pneumonia or disseminated infection
-Amphotericin B or itraconazole
CNS infection
-Amphotericin B or fluconazole
Coccidioidomycosis
Key Teaching Points
Dimorphic fungus
Southwestern US
60% asymptomatic : 40% symptomatic
Pneumonia; CNS infection
Spherules and endospores
Complement fixation serology
Amphotericin or itraconazole (fluconazole)
what fungi has spherules?
Coccidioidomycosis
what fungi has broad based attachments?
Blastomycosis
Yeasts
**Candida species**
Cryptococcus
Trichosporon
Moulds
(Invasive filamentous fungi)
**Aspergillus**
The zygomycetes
Pseudallescheria/Scedosporium
Fusarium
Others
Opportunistic Mycoses
Yeasts and Molds
Candidiasis
Spectrum of infections
encompasses cutaneous, mucosal, and deeply invasive disease→Endogenous in origin
What is the most frequent cause of invasive fungal infections?
Candida (especially in meutropenic host and surgical ICU pts)
4th most common cause of BSIs in US (7.6%) with an associated crude mortality rate of 40%
25-50% of Candida infections occur in pts in ICUs
Candidiasis
Manifestations
fungemia, disseminated disease with multiorgan involvement, or single organ disease
Candida species
C. albicans is the most common species causing infection but the non-albicans species are increasing in frequency
-? Greater risk for invasion→dissemination
-Higher incidence of antifungal drug resistance
--C. glabrata→30% resistant to fluconazole
--C. krusei→91% resistant to fluconazole
Candidiasis
Spectrum of infections
encompasses cutaneous, mucosal, and deeply invasive disease→Endogenous in origin
What is the most frequent cause of invasive fungal infections?
Candida (especially in meutropenic host and surgical ICU pts)
4th most common cause of BSIs in US (7.6%) with an associated crude mortality rate of 40%
25-50% of Candida infections occur in pts in ICUs
Candidiasis
Manifestations
fungemia, disseminated disease with multiorgan involvement, or single organ disease
Candida species
C. albicans is the most common species causing infection but the non-albicans species are increasing in frequency
-? Greater risk for invasion→dissemination
-Higher incidence of antifungal drug resistance
--C. glabrata→30% resistant to fluconazole
--C. krusei→91% resistant to fluconazole
C. glabrata
30% resistant to fluconazole
C. krusei
91% resistant to fluconazole
Candidiasis
Risk Factors for Invasive Infection
Central venous catheters
Exposure to the ICU
Hemodialysis
Documented mucosal colonization
Parenteral hyperalimentation
Systemic antibiotics
Abdominal surgery
Neutropenia >1 wk
Immunosuppressive therapy
Candidiasis
Diagnosis
Identification of “typical” clinical features
Biopsies of involved tissues that reveal yeast and/or pseudohyphae
Cultures of blood or involved tissues
NO useful serologies or antigen detection techniques
Candidiasis
Treatment
Amphotericin B (or lipid formulations), azoles (fluconazole, itraconazole, voriconazole), or echinocandins (caspofungin, micafungin, anidulafungin)
Choice of agent and duration of Rx dependent upon type disease, severity, & causative species
Treatment changes of Candidiasis
Past: Amphotericin B
Currently: Fluconazole or echinocandins
Candidiasis
Key Teaching Points
Yeast
Normal human flora (GI, skin)
Colonizer or pathogen
Associated with ↓PMNs, ↓CMI, or ICU stay
Mucosal disease; fungemia; visceral abscesses
Yeast &/or pseudohyphae
No useful serologies; culture of blood or tissue
Amphotericin, azoles, echinocandins
Aspergillosis
most common form of invasive filamentous fungal disease (IFFD) in humans, with A. fumigatus the most common causative agent (Property of angioinvasion)
Angioinvasion is associated with what fungus?
Aspergillus
(it causes ischemic injury and necrosis)
Aspergillosis
Transmission
Inhalation of airborne spores is the usual route of infection (exogenous in origin)→Pneumonia is most common type of IA (>50% of pts)
Almost all pts with IA have an underlying immunocompromising condition (98%); < 5% of disease occurs in “normal hosts”
Pulmonary Aspergillosis
Allergic bronchopulmonary aspergillosis
Aspergilloma (fungus ball)
Semi-invasive (chronic necrotizing) aspergillosis
Invasive pulmonary aspergillosis
Invasive Pulmonary Aspergillosis (IPA)
Rapidly progressive disease, often disseminated, occurring in markedly immunocompromised pts, esp those with prolonged & severe neutropenia
Classic radiographic findings include a pleural based infiltrate, the “halo” sign (90%), or the “air-crescent” sign (~60%)
Organisms may or may not be demonstrable in sputum or bronchoalveolar lavage fluid specimens
Invasive Aspergillosis
Diagnosis
Clinical features and radiographs may suggest diagnosis but are not definitive
Whenever possible, dx should be based on compatible tissue histo + positive cx
Remember that tissue histology alone is not specific for Aspergillus
Serum antigen detection (galactomannan) is an evolving diagnostic test
Invasive Aspergillosis
Treatment
Primary Rx of proven or probable dz
-Voriconazole
Salvage Rx for non-responders
Lipid formulation of -Amphotericin B
-Caspofungin (Micafungin)
-Itraconazole
-Combination therapies
Role of surgery w/pulmonary & sinus dz
Aspergillus Histology
Acute angle (less than 90 degrees) branching
Septated
Aspergillosis
Key Teaching Points
Mould
Ubiquitous in the environment→Spore
Opportunistic pathogen→↓PMNs>↓CMI
Pneumonia>sinusitis>other
Septated hyphae w/ acute angle branching
Galactomannan antigen assay
Rx: Voriconazole>Ampho>Caspo or Itra
"air cresent" sign
in radiography of the lung, a crescent of gas near the top of a mass lesion, signifying cavitation with a space above the debris; seen in aspergilloma, hydatidoma