Kozel > Lower Respiratory Tract Infections Flashcards
what is the definition of pneumonia?
infection of the alveoli & surrounding lung
what is the definition of bronchitis?
inflammation of the large & mid-sized airways (bronchi)
are viruses or bacteria primarily responsible for most of bronchitis cases?
viruses
what is bronchiolitis?
inflammation of the bronchioles (smallest air passages of the lungs)
are viruses or bacteria primarily responsible for most cases of bronchiolitis?
viruses
RSV = 50-90%
what is acute pneumonia?
inflammation of the lungs d/t MICROBIAL INFECTION of the alveoli & surrounding lung
how long does acute pneumonia last?
days
what are the sx of atypical pneumonia?
moderate amt of sputum
no physical findings of consolidation
moderate WBC elevation
no alveolar exudates
what is chronic pneumonia?
inflammation of the lungs d/t microbial infection of the alveoli & surrounding lung OR non-infectious causes
how long does chronic pneumonia last?
weeks to months
what is pleural effusion & empyema?
accumulation of pus in the pleural cavity
what is a bacterial lung abscess?
infection causing necrosis of lung parenchyma
what are the 4 factors in development of pneumonia?
- defect in host defenses
- exposure to virulent microbe
- overwhelming inoculum
- a combo of these
what are the pulmonary host defenses in the nasopharynx?
nasal hair
anatomy of upper airways
mucociliary apparatus
what are the pulmonary host defenses in the oropharynx?
saliva
cough
bacterial interference
what are the pulmonary host defenses in the trachea & bronchi?
cough & epiglottal reflex
mucociliary apparatus
airway surface liquid
what are the airway surface liquid components?
lysozyme
lactoferrin
what are the pulmonary host defenses in the terminal airways & alveoli?
alveolar lining fluid
alveolar macrophages
neutrophil recruitment
what are the components of the alveolar lining fluid?
surfactant
fibronectin
iron binding proteins
what types of ALOC can impair pulmonary defenses?
stroke seizure drugs anesthesia alcohol
how does ALOC impair pulmonary defenses?
compromises epiglottic closure st pt aspirates oropharyngeal flora
how does cigarette smoke impair pulmonary defenses?
disrupts mucociliary fxn
disrupts macrophages
how does alcohol abuse impair pulmonary defenses?
impairs cough & epiglottic reflexes
increased colonization of oropharynx w/ gram neg bacilli
decreased cellular responses
what type of bacteria colonize the oropharynx when the host pulmonary defenses are impaired?
gram negative bacilli
how do M. pneumoniae, H. influenzae, & viruses impair pulmonary defenses?
interfere w/ or destroy cilia
defective cell fxn
what are the 3 iatrogenic mechanisms that bypass or interfere w/ pulmonary defenses?
endotracheal tubes
nasogastric tubes
respiratory therapy machinery
what age group is susceptible to impaired pulmonary defenses?
old farts
what are the 4 things that impair pulmonary defenses in old people?
- inc # & severity of diseases
- less effective mucociliary clearance & coughing
- increased mucoaspiration
- immune senescence
what are 3 underlying diseases that can impair pulmonary defenses (there are A LOT but these are the 3 listed)?
COPD
immune deficiencies
asplenia
what are the 7 pneumonia syndromes?
- community-acquired acute
- community-acquired atypical
- hospital-acquired
- aspiration
- chronic
- necrotizing & lung abscess
- pneumonia in immunocompromised host
what are the 1st line pathogens assoc w/ community-acquired ACUTE pneumonia?
Strep pneumoniae
Legionella pneumophila
Klebsiella pneumoniae
what are the 2nd line pathogens assoc w/ community-acquired ACUTE pneumonia?
Haemophilus influenzae
Staph aureus
Pseudomonas
what are the 1st line pathogens assoc w/ community-acquired ATYPICAL pneumonia?
mycoplasma pneumoniae
what are the 2nd line pathogens assoc w/ community-acquired ATYPICAL pneumonia?
chlamydia (pneumoniae, psittaci, & trachomatis)
what are the 1st line pathogens assoc w/ hospital-acquired pneumonia?
Klebsiella sp
Legionella pneumophila
what are the 2nd line pathogens assoc w/ hospital-acquired pneumonia?
Pseudomonas sp Staph aureus (usu penicillin resistant)
what are the 1st line pathogens assoc w/ chronic pneumonia?
Nocardia Mycobacterium tb + atypical mycobacterium Histoplasma capsulatum Coccidioides immitis Blastomyces dermatitidis
what are the 1st line pathogens assoc w/ necrotizing pneumonia & lung abscesses?
klebsiella pneumoniae
what are the 2nd line pathogens assoc w/ necrotizing pneumonia & lung abscesses?
Staph aureus
what are the 1st line pathogens assoc w/ pneumonia in immunocompromised hosts?
pneumocystis jiroveci
mycobacterium avium-intracellulare
what is the exposure hx assoc w/ Legionnaires’ disease?
contaminated aerosols (air coolers, hospital water supply)
what is the exposure hx assoc w/ anthrax?
goat hair, raw wool, animal hides
what is the exposure hx assoc w/ brucellosis?
ingestion of unpasteurized milk
what is the exposure hx assoc w/ histoplasmosis?
bat droppings (GUANO!!)(caves) or dust from soil enriched w/ bird droppings
what is the exposure hx assoc w/ leptospirosis?
water contaminated w/ animal urine
what is the exposure hx assoc w/ hantavirus?
rodent droppings, urine, saliva
what is the exposure hx assoc w/ anthrax, plague, & tularemia?
potential bioterrorism exposure
what is the possible zoonotic exposure assoc w/ brucellosis?
employment as abattoir or vet
what is the possible zoonotic exposure assoc w/ anthrax & brucellosis?
exposure to cattle, goats, pigs
what is the possible zoonotic exposure assoc w/ plague?
exposure to rodents in Africa or SW US
what is the possible zoonotic exposure assoc w/ tularemia?
hunting/exposure to rabbits, foxes, squirrels
bites from flies or ticks
what is the possible zoonotic exposure assoc w/ psittacosis?
exposure to birds
what is the possible zoonotic exposure assoc w/ pasteurella multocida & coxiella burnetii (Q fever)?
exposure to infected dogs & cats
what is the possible zoonotic exposure assoc w/ Q fever?
exposure to infected goats, cattle, sheep, domestic animals, & their secretions (milk, amniotic fluid, placenta, feces)
what is a possible travel exposure assoc w/ coccidioidomycosis?
San Joaquin Valley southern CA SW TX southern AZ NM
what is a possible travel exposure assoc w/ histoplasmosis & blastomycosis?
Mississippi or Ohio River Valleys
Caribbean
central America
Africa
what is a possible travel exposure assoc w/ SARS & avian influenza?
china
what is a possible travel exposure assoc w/ MERS-CoV?
Arabian peninsula
what is a possible travel exposure assoc w/ melioidosis?
SE Asia
W Indies
Australia
Guam
what is the pathogenesis of cystic fibrosis?
lung obstructed by viscous secretions
what causes airway wall damage in cystic fibrosis?
persistent bacterial infection
what are the 4 microbes assoc w/ CF?
- staph aureus
- pseudomonas aeruginosa
- burkholderia cepacia complex
- H. flu
what are the 3 treatment guidelines for CF?
- REMOVE viscous & purulent airway SECRETIONS
- control bacterial infection w/ ABX
- provide proper nutrition for HOST DEFENSE
what things in a pt hx suggest pneumonia?
- sx
- clinical setting
- defects in host defense
- possible pathogen exposure
T/F: sensitivity & specificity of physical exam findings is high for pneumonia
FALSE relatively low (50-75%)
what 2 general things during physical exam can be suggestive of pneumonia?
systemic > fever
chest exam findings
what are the 5 diagnostic tests you can use for pneumonia?
- radiology
- examination of sputum
- examination of pleural effusions
- bronchoscopy
- blood culture, serology, urine studies (incl ag detection)
what is the gold standard for making a clinical diagnosis of pneumonia?
Radiology!
what is the PRIMARY CAUSE of bacterial pneumonia & meningitis?
strep pneumo
what are the 4 characteristic sx of pneumococcal pneumonia?
abrupt onset
fever
sharp pleural pain
bloody rusty sputum
T/F: pneumococcal pneumonia is a disease of otherwise healthy pts
FALSE
“a disease of compromised host > age, physical condition, genetics (sickle cell)”
where does pneumococcal pneumonia localize?
lower lobes
i.e. lobar pneumonia
have you gone over the other set of Kozel flash cards?
you should! (mainly for lab dx & pneumococcal vax)
what does treatment approach of pneumococcal pneumonia vary w/?
site of infection
setting of infection
pt condition
is klebsiella pneumoniae encapsulated?
YEP
how does klebsiella pneumoniae cause pneumonia?
necrotic destruction of alveolar spaces
what is the sputum like in klebsiella pneumonia?
thick
bloody
MUCOID!!!
T/F: pts w/ klebsiella pneumonia are usu compromised
TRUE
immunosuppressed or impaired respiratory defenses
what are the 4 other infections that klebsiella pneumoniae can cause?
UTI
wound infection
bacteremia
meningitis
what is the 2nd most common cause of UTI among oldies after E. coli?
klebsiella pneumoniae
what is the colony morphology of klebsiella pneumoniae?
mucoid
what word should you associate w/ klebsiella pneumoniae?
MUCOID
what samples can you use for lab dx of klebsiella?
sputum
blood
pus
CSF
how do you isolate klebsiella pneumoniae (medium)?
typical enteric medium
is klebsiella pneumoniae an enterobacter?
YES
how do you identify klebsiella on media?
fermenter
mucoid colonies
typical enteric differential media
T/F: healthy people get klebsiella pneumonia
FALSE
disease of SICKIES!
where is klebsiella mainly spread?
hospital
HOW is klebsiella spread?
person to person
OR
contamination of ventilators, IV catheters, wounds
how do you prevent klebsiella pneumonia?
strict attn to infection control measures
T/F: klebsiella is easily treated w/ abx
FALSE
highly resistant!
what are the 4 mechanisms of resistance of klebsiella?
- overpdtion of beta lactamase
- extended spectrum beta lactamases
- efflux pump
- carbapenem resistance
what is CRKP?
carbapenem-resistant klebsiella pneumoniae
what encodes carbapenem resistance?
blaKPC gene
what does CRKP do w/ beta lactam abx?
hydrolyzes ALL OF THEM
T/F: klebsiella pneumoniae is resistant to beta lactamase inhibitors
TRUE
what are the treatment options for CRKP?
polymyxins or sometimes nothing
what is treatment of klebsiella pneumoniae dependent on?
susceptibility testing
gotta find an abx that works
T/F: Legionella pneumophila stains really well
FALSE
stains poorly w/ common reagents
what 2 things does Legionella pneumophila require to grow?
cysteine
iron
where does Legionella pneumophila replicate?
inside macrophages
what does Legionella pneumophila do inside the macrophage?
prevents phagolysosome fusion
how many legionella species infect humans?
20
how many legionella species are there?
50+
what is Legionnaires’ disease?
severe acute pneumonia
what are the sx of Legionnaires’ disease?
fever
non-pdtive cough
SOB
myalgias
what are the risk factors of Legionnaires’ disease?
50+ yo
smoker (now or previously)
chronic lung disease
weakened immune system, diabetes, kidney failure, immunosuppression
what is the mortality rate of Legionnaires’ disease?
15-20%
this is high!
what is Pontiac fever?
mild form of respiratory infection
NOT pneumonia!
what causes Pontiac fever?
exposure to aerosol
high attack rate
what is the mortality of pontiac fever?
very low, <1%
what cells are infected in Legionnaires’ disease?
alveolar macrophages
monocytes
alveolar epithelial cells
what does inhibiting phagolysosomal fusion prevent in Legionnaires’ disease?
exposure to superoxide H2O2 & OH radicals (ROS)
what is the eventual immunity assoc w/ Legionnaires’ disease?
cell-mediated
how do you dx Legionnaires’ disease?
urinary ag test
x-ray/physical exam to dx pneumonia
expectorated sputum or endotracheal aspirate
what is the most commonly used dx tool in Legionnaires’ disease?
urinary ag test
what does the urinary ag test detect for Legionnaires’ disease?
serogroup 1 LPS
what serogroup is responsible for 80-90% of community acquired infections of Legionnaires’ disease?
serogroup 1
what % of hospital-acquired infections are d/t serogroup 1?
<50%
T/F: culture of legionella pneumophilae requires special media
TRUE
where is legionella pneumophila found?
aqueous environments > warm water
what is the host of legionella pneumophila?
free-living amoebas
how do you acquire legionella pneumophila?
exposure to contaminated aerosols > air conditioning, cooling towers, hot tubs, misters, etc
T/F: legionnaires disease is common
true!
20k-100k cases in US/yr (estimated)
is subclinical infection w/ legionella pneumophila common?
YES
indicated by serological testing
why is legionella pneumophila infection often hospital acquired?
high # of high-risk pts
how do you prevent & control legionnaires’ disease?
routine surveillance for microbial burden
clean & disinfect as appropriate
do you do susceptibility tests for legionnaires’ disease?
NOPE
bc it’s too hard to grow the bacterium
why are many abx ineffective against legionnaires’ disease?
bc they have poor penetration of macrophages
what abx can you use to treat legionnaires’ disease?
macrolides > azithromycin
fluoroquinolones > levofloxacin
tetracyclines > doxy
how do you treat pontiac fever?
you don’t
what is the smallest free-living bacterium?
mycoplasma
what is unique about mycoplasma’s cell wall?
it doesn’t have one
so it is RESISTANT to abx that target the cell wall
what does the cell membrane of mycoplasma contain?
sterols from the host
e.g. cholesterol
what does growth in culture of mycoplasma require?
medium containing sterols
e.g. animal serum
what is the pathogenesis of mycoplasma?
adheres to respiratory epithelium via attachment organelle > destroys cilia then ciliated epithelial cells > irritation & secondary infection
what causes a persistent cough w/ mycoplasma infection?
the irritation & secondary infection
what is the primary adhesin for mycoplasma?
P1 protein
where are the receptors for mycoplasma?
host cells
T/F: most infection w/ mycoplasma is asymptomatic
TRUE
what are the 2 clinical diseases assoc w/ mycoplasma?
tracheobronchitis
primary atypical pneumonia
what is the most common clinical disease assoc w/ mycoplasma?
tracheobronchitis
what are the sx of tracheobronchitis?
low-grade fever
malaise
HA
non-productive cough
what is primary atypical pneumonia d/t mycoplasma like for the pt?
it’s okay
pts not terribly ill
“walking pneumonia”
what is more impressive than clinical signs in mycoplasma primary atypical pneumonoia?
patchy bronchopneumonoia on chest radiograph
how is mycoplasma pneumonia usually diagnosed?
empirically, based on clinical signs
can you use microscopy for mycoplasma pneumoniae?
NOPE
and it stains poorly too
what does mycoplasma pneumoniae require for growth?
special media supplemented w/ serum (sterols)
PLUS it grows really slow (2-6 weeks)
so DON’T CULTURE IT
why don’t you use serology to dx mycoplasma pneumoniae?
lacks sensitivity & specificity (both complement fixation & cold agglutinin)
how does cold agglutinin serology work?
IgM ab bind to I blood group ag on human RBCs at 4C
how is mycoplasma pneumoniae spread?
respiratory droplets
is mycoplasma pneumoniae zoonotic?
nope
strictly human
T/F: mycoplasma pneumoniae incidence is seasonal
FALSE
all populations are susceptible to mycoplasma pneumoniae, but what age group is primarily infected?
children 5-15 yo
what are the 3 best treatments for mycoplasma pneumonia?
macrolide (erythro/azithro)
tetracycline (doxy)
fluoroquinolone
which abx can you NOT use for kids that have mycoplasma pneumonia?
tetracyclines
which abx is most expensive to treat mycoplasma pneumonia?
$$$: fluoroquinolones
$: tetracyclines
what are the 5 types of endemic dimorphic fungi?
histoplasmosis blastomycosis coccidiomycosis paracoccidioidomycosis penicilliosis
where does histoplasma capsulatum live?
soil w/ lots of Nitrogen i.e. bird & bat poop
where is H. capsulatum found in the world?
OH & Mississippi river valleys
Mexico, C & S America
what is a major risk factor of H. capsulatum in S & C America & Mexico?
AIDS
where is H. capsulatum var. duboisii found in the world?
tropical Africa
what are the 4 steps of natural history of H. capsulatum?
- inhale microconidia
- germination into yeast
- intracellular growth in lungs
- stay local or disseminate
where does h. capsulatum grow in your body?
intracellular in the lungs
what is the primary host defense against histoplasmosis?
cellular immunity
what type of histoplasmosis is common in endemic areas?
acute pulmonary
what are the 4 types of histoplasmosis?
acute pulmonary
chronic pulmonary
progressive disseminated
African
what are the sx of acute pulmonary histoplasmosis?
usu asymptomatic or flu-like
if sick, fever, HA, non-pdtive cough, chills, chest pain
what are the sx of chronic pulmonary histoplasmosis?
fever, pdtive cough, chest pain, CAVITARY LESIONS
what is affected in progressive disseminated histoplasmosis?
multiple organ systems
what are the risk factors for progressive disseminated histoplasmosis?
55+ yo
immunosuppression
what variant of histoplasma is implicated in African histoplasmosis?
h. capsulatum var. duboisii
what are the most commonly involved organ systems in African histoplasmosis?
skin & skeleton
what is the histopathology of histoplasmosis?
small budding yeasts w/i macrophages
does histoplasma display temp-dependent dimorphism?
YEP
what does histoplasma look like at 37 C?
yeast
small, oval, budding
what is the mycelium form of histoplasma (what does it look like at 20 C)?
tuberculate macroconidia
how does the ag immunoassay for histoplasmosis work?
detects cell wall polysaccharide (reference lab only)
what is the best sample for the ag immunoassay for histoplasmosis?
urine
how does serology for histoplasmosis work?
tests for serum ab via complement fixation or precipitation
what is the false seropositive rate of histoplasmosis in endemic areas?
10%
what % of pts w/ acute histoplasmosis develop the ab?
75%
what test has little value for diagnosing histoplasmosis but is useful for epidemiology?
skin test
what determines delayed hypersensitivity for histoplasmosis?
histoplasmin skin test
T/F: most cases of acute pulmonary histoplasmosis require no treatment
TRUE
what does the extent of treatment for histoplasmosis vary with?
severity of disease
what antifungals can you use for histoplasmosis?
itraconazole
amphotericin B or liposomal amphotericin B
where does blastomyces dermatitidis live?
soil w/ decaying organic matter
where is blastomyces dermatitidis found geographically?
OH & Mississippi river valleys
SE US
what does the endemic area of blastomyces dermatitidis overlap w/?
histoplasmosis
how does blastomyces dermatitidis get into your body?
inhalation of conidia from environmental site
what is the natural hx of blastomyces dermatitidis?
- inhale conidia
- germinate into yeast
- grow in lungs
- remain local or disseminate
what animal is highly susceptible to blastomyces dermatitidis infection?
dogs
but they are NOT a reservoir
what is the primary host defense against blastomycosis?
cellular immunity
what are the 3 types of blastomycosis?
acute pulmonary
disseminated
infection in immunocompromised host
what % of cases of acute pulmonary blastomycosis are asymptomatic?
50%
what is the clinical course of acute pulmonary blastomycosis?
asymptomatic but may progress to fulminant respiratory disease w/ abrupt onset of myalgia, arthralgia, chill, fever
what is most often involved in disseminated blastomycosis?
skin
what sites may also be affected in disseminated blastomycosis?
lymph nodes bones joints prostate CNS
what does infection of blastomycosis in an immunocompromised host look like?
aggressive! but less common than other fungi
what is the histopathology of blastomycosis?
broad-based large budding yeasts
what does blastomycosis look like at 20C?
non-specific mycelium
what does blastomycosis look like at 37C?
small oval broad-based budding yeasts
how do you confirm blastomycosis culture?
PCR
what 2 tests are USEFUL in diagnosing blastomycosis?
culture
ag immunoassay of urine
what does the ag immunoassay of urine detect in blastomycosis?
detects cell wall polysaccharide (reference lab only) but it’s LOW SPECIFICITY bc it’s cross-reactive w/ other fungi
what meds can you use to treat blastomycosis?
itraconazole
lipid amp-B
what med should you use for mild/moderate blastomycosis?
itraconazole
what med should you use for severe blastomycosis or blastomycosis in an immunocompromised pt?
lipid amp-B
what does coccidioides immitis look like in soil?
mycelium w/ “barrel shaped” arthroconidia
what does coccidioides immitis look like in tissue?
endosporulating spherules
what does coccidioides immitis live in?
soil of dry, low-rainfall areas
what is the geographic distribution of coccidioides immitis?
SW US (CA, AZ, NM)
Mexico
C & S America
there are 2 species of coccidioides. are they distinguishable?
nope
what species of coccidioides is in California?
immitis
what species of coccidioides is found in all infectious OUTSIDE of California?
posadasii
what is the natural history of coccidioides immitis?
inhale arthroconidia > germinate in lungs > form spherules > stay local or disseminate
what is valley fever?
coccidioidomycosis
what is the primary host defense against coccidioidomycosis?
cellular immunity
what are the 3 types of coccidioidomycosis?
primary pulmonary
pulmonary nodules & cavities
extrapulmonary dissemination
in endemic areas, what % of ppl have primary pulmonary coccidioidomycosis?
30-60%
how long after exposure do you get symptoms of coccidioidomycosis?
7-21 days (1-3 weeks)
what are the sx of coccidioidomycosis?
cough chest pain SOB fever fatigue
what % of pulmonary coccidioidomycosis infections get pulmonary nodules & cavities?
4%
what are the sx of pulmonary nodules & cavities of coccidioidomycosis?
pleuritic pain
cough
hemoptysis
in 0.5% of the general pop that gets primary coccidioidomycosis infection progresses to what?
extrapulmonary dissemination
what are the risk factors for extrapulmonary coccidioidomycosis dissemination?
immunosuppression
genetics (African or Filipino descent)
what is the most serious form of extrapulmonary coccidioidomycosis dissemination?
coccidioidal meningitis
what establishes diagnosis of coccidioidomycosis?
endosporulating spherules in sputum, exudates, or tissue
can you culture coccidioides?
you can, but it’s less useful than other fungi AND it’s an EXTREME BIOHAZARD!
is the mycelium form of coccidioides specific?
no
but it does have characteristic arthroconidia (?)
what test can be useful in diagnosing coccidioidomycosis in pts w/ non-pdtive cough?
serology > tests for serum ab
what % of pts w/ acute coccidioidomycosis develop ab?
75%
what % of normal ppl are positive for coccidioidomycosis in endemic areas?
10%
what test is useful for epidemiology but not for diagnosis of coccidioidomycosis?
coccidioidin skin test
what does coccidioidin skin test determine?
delayed hypersensitivity
what are the treatments for coccidioidomycosis?
oral azole (fluconazole, itraconazole, ketoconazole) amp-B
why is pneumocystis classified as a fungus?
rRNA sequences
what does pneumocystis lack?
ergosterol
what species of pneumocystis lives in rats?
carinii
what species of pneumocystis lives in humans?
jirovecii
is there an in vitro culture system for pneumocystis?
nope
T/F: the life cycle of pneumocystis is sexual only
FALSE
has sexual & asexual components
which microbial forms of pneumocystis are found during human infection?
all of them (trophic, sporozoite, & spores)
what microbial form of pneumocystis is “free”?
trophic
what microbial form of pneumocystis is precystic?
sporozoite
what do pneumocystis cysts contain?
up to 8 intracystic bodies
what are the 3 microbial forms of pneumocystis?
free (trophic)
sporozoite (precystic)
cysts (spores)
is natural resistance to pneumocystis high or low?
high
what happens if a host is compromised and infected w/ pneumocystis?
organisms proliferate & gradually fill alveolar lumens
what happens in the alveoli w/ pneumocystis infection?
foamy exudate in alveolar space
AND
intense interstitial infiltrate of plasma cells
what does pneumocystis infection progress to after alveolar infiltration?
interstitial fibrosis
edema
what classical presentation of pneumocystis occurs in debilitated infants?
interstitial plasma cell pneumonitis
what sx do immunosuppressed pts get w/ pneumocystis pneumonia?
SOB
fever
non-pdtive cough
what sx do HIV pts get w/ pneumocystis pneumonia?
similar to immunosuppressed presentation but SUBTLE
what sx do infants get w/ pneumocystis pneumonia?
insidious onset
respiratory distress
cyanosis
why is the mortality rate of PCP high if untreated?
respiratory failure
how do you dx PCP?
empirically via clinical signs in an immunosuppressed pt
or
microscopy
what is most useful in diagnosing PCP?
microscopy
what is the sensitivity of BAL fluid staining for PCP?
90-100%
what forms does the Wright-Giemsa stain work on for PCP?
all forms
what stain can you use for the cyst form?
silver stain
what does the cyst form stain look like?
(silver stain)
crushed ping pong ball
what age does ubiquitous colonization of pneumocystis occur at?
early in life, first 2 years
how is pneumocystis communicable (what route)?
airborne
how does immunocompromise allow for pneumocystis infection?
reactivation of latent infection
OR
progression of recently acquired infection
what are the risk factors for PCP?
malnourished/preemie babies SCID hyper-IgM syndrome immunosuppressive meds AIDS
what has made PCP less frequent in AIDS pts?
HAART
what is the tx for PCP?
TMP-SMZ (prophylaxis AND treatment)
who should you use chemophrophylaxis for against PCP?
AIDS pts w/ CD4 counts <200/mm3
who discovered mycobacteria?
Koch
what does mycobacteria have in the cell wall?
mycolic acid
what are mycolic acids?
long fatty acids
what properties do mycolic acids confer to mycobacteria?
acid-fast resistant to gram stain resistant to detergents & hydrophobic abx survive in macrophages "cording" arrangement
how is the cell wall structure of mycobacteria like a gram+?
inner membrane
thick peptidoglycan layer
NO outer membrane
how the cell wall structure of mycobacteria NOT like gram+?
LAM
additional lipids
what is LAM?
lipoarabinomannan
functionally similar to O-ag
how much of the cell wall weight (%) of mycobacteria is d/t lipids?
60%
what causes TB?
m. tuberculosis complex
what are the 5 components of the m. tuberculosis complex?
m. tuberculosis
m. bovis
bacille Calmette-Guerin
m. africanum
m. canetti
what species cause TB in Africa?
m. africanum (duh)
m. canetti
what species causes TB in cattle?
m. bovis
how is m. bovis spread to humans?
eating/drinking contaminated dairy products
what is bacille calmette-guerin?
less virulent strain of m. bovis
what is the mycobacteria species that is not part of the m. tuberculosis complex?
m. leprae
what is another name for atypical mycobacteria?
non-TB mycobacteria
what is cord factor?
trehalose dimycolate
subset of cell wall mycolic acids
glycolipid cell wall component
where can you find cord factor?
in the cell wall of VIRULENT STRAINS
what does cord factor bind to?
macrophage surface receptor called MINCLE (minkus!)
what does cord factor do once it binds (3 things)?
blocks macrophage activation by IFN-gamma
induces secretion of TNF-alpha
causes cord formation
is tuberculosis intra or extracellular?
INTRACELLULAR
what must tuberculosis avoid being killed by?
macrophages
what are the 2 types of TB?
primary
reactivated
how does reactivation TB happen?
waning/loss of cellular immunity allows for bacterial outgrowth
what is the response to reactivation TB?
destructive delayed-type hypersensitivity
in primary TB, what phagocytizes the bacteria?
alveolar macrophages
how does primary TB survive in the body?
prevents fusion of phagosome w/ lysosome (in macrophage)
what happens to infected macrophages in primary TB?
secrete cytokines (IL-12 & TNF-alpha)
what do the cytokines from primary TB-infected macrophages drive?
drive T cells to differentiate into Th1 cells that secrete IFN-gamma
in primary TB, what does IFN-gamma do?
activates infected macrophages
promotes phagosome-lysosome fusion & killing via ROS & RNS
in primary TB, what can the delayed-type hypersensitivity response lead to?
granuloma
what is a primary TB granuloma composed of (5 things)?
lymphocytes macrophages epithelioid cells fibroblasts giant cells
how is primary TB resolved?
either the bacteria go dormant or you have to kill them
what are the sx of primary TB?
usu asymptomatic
OR can be mild fever & malaise
what can you see on radiographs of primary TB?
mid-lung infiltrates
hilar lymphadenopathy
what 2 things can primary TB progress to?
reactivation
dissemination
what % of pts w/ primary TB reactivate?
10%
what pt population gets reactivation TB?
men 50+yo
what disease is reactivation TB most often assoc w/?
immunosuppression
AIDS is most common
what are the sx of reactivation TB?
dry cough that becomes productive & mixed w/ blood (hemoptysis) fever malaise sweating weight loss
what do the lungs look like in reactivation TB?
cavities in apices (it rhymes!)
cavities have TONS of bacteria
what happens if you don’t treat reactivation TB?
death in 2-5 years
what disorders can lead to a more rapid course of reactivation TB?
AIDS
other T cell compromise
make sure you look at SLIDE 69 > extrapulmonary TB bc idk how to make a card about it
okie dokie
what allows for a presumptive dx of TB?
radiology
why is radiology important w/ TB?
central to dx
asses extent & character of disease
evaluate response to tx
on radiology, what is highly suggestive of TB?
patchy or nodular infiltrate in the lung apices, esp if the infiltrate is cavitary
what are the 2 things you can do to immunodiagnose TB?
skin test
IFN-gamma-release assay
what can you do on microscopy to dx TB?
acid-fast stain
when you do a TB skin test, what do you inject & where do you inject it?
INTRADERMAL injection of 5 tuberculin units of PPD
what is PPD?
purified protein derivative
cell wall protein
how long after the injection should you look at the skin site?
48-72 hours
what are you looking for w/ a TB skin test?
INDURATION
NOT ERYTHEMA!
what are the 3 cutoffs in size of the TB skin test reaction?
5 mm cutoff for immunosuppressed or recent contacts
10 mm cutoff for other high risk groups
15 mm cutoff for low risk groups
what does a positive TB skin test imply?
INFECTION NOT DISEASE (necessarily)!!!
what can cause a false positive TB skin test?
infection w/ non-mycobacterium TB mycobacteria (non-Mtb)
what can cause a false negative TB skin test?
generalized illness or immunosuppression
what are not necessarily recommended for negative skin TB tests, even though they can identify anergy?
additional skin tests w/ candida or mumps ag
how can you identify cell mediated immunity to TB (what test)?
IFN-gamma release assay
how do you do the IFN-gamma release assay?
incubate whole blood w/ Mtb ag
measure the release of IFN-gamma
what are the antigens in the IFN-gamma release assay (generally)?
3 Mtb proteins NOT FOUND in NON-Mtb species
what are the 3 advantages to the IFN-gamma release assay?
no rxn in ppl who received BCG
no need to return to have skin test eval
no booster effect w/ repeat testing
what are the 2 disadvantages to the IFN-gamma release assay?
$$$$$
lab infrastructure
what is now recommended by the CDC to detect Mt infection & surveillance?
IFN-gamma release assay
what do you do with a smear of a suspected TB sample?
cover w/ stain heat it up rinse decolorize w/ acid alcohol counterstain w/ methylene blue
what conc is required for Mtb positivity on a slide?
10,000 Mtb/mL is positive
>/= 10 Mtb on a slide = optimal
a single organism is highly suggestive
what dyes are the most sensitive for Mtb?
fluorescent
what should you use in resource limited countries to dx TB?
LED microscopes
what stain is hot acid fast?
Ziehl-Nielsen (cause Zayn is the hottest dude in one direction)
what stain is cold acid fast?
Kinyoun (Kin cold)
what stain is fluorochrome acid fast?
Truant (T & F both have crosses)
how do nucleic acid-based tests for TB work?
PCR amplification of a clinical sample
what is the sensitivity of nucleic-acid based tests (compared to other diagnostic tools, not a number)?
intermediate btwn acid fast & culture
what are the 2 advantages to the nucleic acid-based tests for TB?
simultaneously assess resistance to RIFAMPIN (surrogate for MDR)
AND
can be self-contained (Cephid) > advantage for resource-limited countries
what are the 3 disadvantages of nucleic acid-based tests for TB?
sensitivity & ease of use varies
some tests require advanced lab infrastructure
too $$$ for resource-limited
what is the GOLD STANDARD for TB dx?
CULTURE!
what can culture of TB detect (concentration)?
10-100 Mtb/mL (which is a lower conc than acid fast so it’s BETTER than acid fast)
what do samples from contaminated sites require?
decontamination
can mycobacteria survive decontamination?
yes
mild decontamination
what are the 2 culture media for TB?
solid
AND
liquid
what are the 2 types of solid culture media for TB?
Lowenstein-Jensen
Middlebrook
how long does TB culture on solid medium take?
3-8 weeks
how long does TB culture on liquid medium take?
1-3 weeks
how can you identify TB cultures?
colony morphology
biochemical tests
species-specific molecular probes
what are the 3 ways to detect abx sensitivity of TB?
agar proportion
liquid broth systems
molecular tests
how does the agar proportion for TB abx sensitivity work?
determines percentage of resistant Mtb
why are the liquid broth systems for TB abx sensitivity good?
provide FASTER results
what do the molecular tests for TB abx sensitivity detect?
resistance to RIFAMPIN
what % of the world’s population is infected w/ TB?
33% (1/3)
how many new cases & deaths does TB cause annually?
9 million new cases
2 million deaths
how many new cases of TB are there in the US per year?
11,000
most cases of TB in the US are what kind of TB?
reactivation
most are foreign-born
how is TB spread?
person-to-person (humans ONLY) via airborne droplets
how are most TB infections dealt with in the body (very generally)?
immune system
who is at risk of exposure to TB via close contact?
healthcare workers
“institutional exposure”
exposure to TB depends on what 2 things?
closeness of contact
infectiousness of source (i.e. cavitary TB)
what is the biggest risk factor for TB?
immunosuppression
what are the 4 first line drugs used in combo for TB treatment?
isoniazid rifampin ethambutol pyrazinamide (IREP)
how does isoniazid work?
inhibits synthesis of mycolic acid
how does rifampin work?
inhibits DNA-dependent RNA polymerase
how does ethambutol work?
inhibits cell wall synthesis
how does pyrazinamide work?
who knows
“mechanism not well understood”
what “other agents” does Kozel list that you can also use to treat TB?
aminoglycosides
fluoroquinolones
how do you combat the emergence of abx resistance in TB?
use 4 drugs
what are the 2 other treatment things you can do for TB?
directly-observed treatment
consulting current guidelines
what is MDR TB resistant to?
at least
isoniazid AND rifampin
in what population was MDR TB first observed?
in AIDS & homeless people in NYC & Miami
what causes MDR TB?
interrupted abx course
drug levels insufficient to kill 100% of bacteria
what is XDR TB?
EXTENSIVELY drug resistant TB
how does XDR TB start?
as MDR TB
what is XDR TB resistant to?
isoniazid rifampin quinolones AND at least 1 second-line drug
where can you find XDR TB?
most regions of the world
can you treat XDR TB?
maybe?
“potentially untreatable”
what is the BCG vaccine?
LIVE vaccine of Bacille Calmette-Guerin (less virulent strain of M. bovis)
how many people got BCG vaccine?
3-5 BILLION
more than any other vaccine
who gets the BCG vax?
infants in endemic countries
NOT in the US or other countries w/ low incidence of TB
what positive effect has the BCG vax had?
reduced incidence of disseminated TB in kids
what does the BCG vax do with the TB skin test?
produces false-positive
but skin test reactivity is low
what does BCG NOT consistently reduce?
incidence of adult pulmonary disease
what can happen if you give the BCG vax to pts w/ primary or acquired immune deficiency (AIDS)?
BCG disease
but not autism!
are non-TB mycobacteria (NTM) & atypical mycobacteria the same thing?
yup
how do you classify NTM?
growth rate
pigmentation (Runyon)
what are the 5 major disease producing species of NTM?
M. kansasii M. fortuitum M. abscessum M. ulcerans M. marinum (how fortuitous that in kansas, you can get an abscess and an ulcer at the marina)
how do you get NTM?
environmental sources i.e. tap water
how many species TOTAL are there of NTM that cause disease?
> 50
what diseases/syndromes can result from NTM?
- chronic bronchopulmonary disease
- skin & soft tissue disease
- lymphadenitis
- disseminated disease in immunosuppressed pts (AIDS)
how do you dx NTM?
same as Mtb
how do you treat NTM?
it depends on the species
“tx varies dramatically w/ various NTM species”
which NTM has a high degree of abx resistance?
m. abscessum
what are the abx resistance mechanisms of m. abscessum?
abx modifying enzymes
abx degrading enzymes
target modification
efflux pumps
what abx is m. abscessum resistant to via abx modifying enzymes?
aminoglycosides
what abx is m. abscessum resistant to via abx degrading enzymes?
beta lactams
what abx is m. abscessum resistant to via target modification?
macrolides
how do you treat m. abscessum?
long-term abx
surgical intervention to drain any lesions
what case study is assoc w/ m. abscessum?
medical tourism for cosmetic surgery in the dominican republic
what are the 2 species in the mycobacterium avium complex (MAC)?
m. avium
m. intracellulare
(birds INSIDE a birdcage)
what are the 4 diseases assoc w/ MAC?
- primary infection
- chronic localized pulmonary disease
- disseminated disease in advanced AIDS
- cervical lymphadenitis
can you get reactivation disease w/ MAC?
NOPE
what kinds of pts get chronic localized pulmonary disease d/t MAC?
pts have intact immunity
smokers
COPD pts
which AIDS pts get disseminated disease?
the ones w/ CD4 <100/mm3
it was very common prior to HAART
is microscopy for MAC good?
nope
lacks sensitivity & specificity
can you culture MAC?
yep
PLUS blood culture for disseminated disease
how do you get MAC?
from the environment via inhalation or ingestion
T/F: MAC spreads via person-to-person transmission
FALSE
none of that
what environmental sources can harbor MAC?
natural water sources
indoor water systems
pools
hot tubs (great)
T/F: treating MAC is easy peasy lemon squeezy
FALSE
very difficult!
high treatment failure rate!
what abx can you use for MAC?
clarithromycin or azithro PLUS ethambutol PLUS rifabutin (C you in the ER cause you got MAC)
what should you do for pts if they have a CD4 <50 cells/mm2?
azithromycin prophylaxis for MAC
T/F: Nocardia is WEAKLY acid fast
TRUE
what shape is Nocardia?
filamentous rods
what species of Nocardia should you be worried about?
Nocardia asteroides complex (asteroides, brasiliensis)
Rhodococcus
Gordonia
Tsukamurella
which Nocardia species are RARE and implicated in opportunistic infections?
Gordonia
Tsukamurella
which species of Nocardia is uncommon and involved in pulmonary, cutaneous, and CNS disease?
Rhodococcus
what is the virulence of nocardia related to?
ability to avoid intracellular killing
what inactivates the toxic metabolites of nocardia?
catalase
superoxide dismutase
what does cord factor do in nocardia?
prevents intracellular killing
prevents phagosome-lysosome fusion
what 2 disease classes can Nocardia cause?
bronchopulmonary
cutaneous
who gets bronchopulmonary nocardia disease?
immunocompromised pts
what is the course of bronchopulmonary nocardia infection?
disseminates to the CNS or skin
what is a mycetoma?
cutaneous Nocardia infection involving chronic granulomatous destruction of extremities
how can cutaneous nocardia manifest?
mycetoma
lymphocutaneous infection
cellulitis
subQ abscess
what does nocardia in sputum look like?
beaded filaments!
how do you distinguish Nocardia from actinomyces?
ACID-FAST STAIN!
Nocardia is weakly acid fast
how do you culture Nocardia?
special media
notify lab
what does nocardia look like on agar culture?
aerial hyphae (looks like cotton)
when you do a molecular analysis of nocardia, what are you doing?
sequencing the rRNA
where is nocardia ubiquitous?
soil that has organic matter
how do you get nocardiosis?
inoculation of skin or inhallation
who gets nocardiosis?
mostly immunocompromised pts
what is the primary abx for nocardiosis?
TMP-SMX
how do you treat nocardiosis in an immunocompromised pt?
TMP-SMX
PLUS
amikacin OR imipenem OR broad-spectrum cephalosporin
how long do you treat nocardiosis for?
12 months!
how can you treat a really extensive nocardia infection?
surgical mgmt
FUCK YEAH YOU JUST WENT THROUGH 443 CARDS ABOUT FUCKING STUPID ASS BACTERIA!
YOU DID IT! YOU’RE AMAZING!