Lower Respiratory Tract Infections-Kozel Flashcards
1
Q
What is the infection of the tonsils?
What is a “sore throat” or infection of the pharynx?
What is an infection of the trachea?
What is an infection of the larynx?
What is an infection of the small airways- the bronchioles?
What is an infection of the larynx?
What is an inflammation of the pleura often caused by an infection?
What is an infection of the large airways-the bronchi?
A
- tonsilitis
- pharyngitis
- tracheitis
- laryngitis
- bronchiolitis
- laryngitis
- pleurisy
- bronchitis
2
Q
What mostly causes bronchitis?
Bronchiolitis?
A
Viruses
Viruses (RSV 50-90%)
3
Q
What is this:
Inflammation of lungs caused by microbial infection of the alveoli and surrounding lung; present for days
A
Acute pneumonia
4
Q
What is this:
Characterized by moderate amounts of sputum, absence of physical findings of consolidation, only moderate elevation of WBC, and lack of alveolar exudates
A
atypical pneumonia
5
Q
What is this:
Inflammation of lungs caused by microbial infection of the alveoli and surrounding lung or non-infecious causes; present for weeks to months
A
Chronic pneumonia
6
Q
What is this:
accumulation of pus in the pleural cavity
A
Pleural effusion and empyema
7
Q
What is this:
infection causing necrosis of lung parenchyma
A
Bacterial lung abscess
8
Q
What are three factors in development of pneumonia?
A
- Defect in host defenses
- Exposure to particularly virulent microbe
- Overwhelming inoculum
(can involve one or more of the above)
9
Q
What are the pulmonary host defenses in the nasopharynx?
A
Nasal hair
Anatomy of upper airways
Mucocilliary apparatus
10
Q
What are the pulmonary host defenses in the oropharynx?
A
Saliva
Cough
Bacterial inferference
11
Q
What are the pulmonary host defenses in the trachea and bronchi?
A
Cough, epiglottal reflexes
Mucocilliary apparatus
Airway surface liquid (lysozyme (kills peptidoglycan in cell wall of gram positive, lactoferrin (binds iron that bugs need)
12
Q
What are the pulmonary host defenses in the terminal airways and alveoli?
A
Alveolar lining fluid (surfactant, fibronectin, iron-binding proteins)
Alveolar macrophages
Neutrophil recruitment
13
Q
How can alterations in level of consciousness impair pulmonary defenses?
A
Stroke, seizures, drug intoxication, anesthesia, alcohol abuse can
compromise epiglottic closure → aspiration of oropharyngeal flora
14
Q
How can cigarette smoke impair pulmonary defenses?
A
Disrupts mucociliary function
Disrupts macrophage activity
15
Q
How can alcohol abuse impair pulmonary defenses?
A
- Impairs cough and epiglottic reflexes
- Increased colonization of oropharynx with gram-negative bacilli
- Decreased cellular responses
16
Q
How can infection (M. pneumoniae, H. influenzae, viruses) impair pulmonary defenses?
A
- Interfere with or destroy cilia
- Defective cell function
17
Q
What are the iatrogenic manipulations that bypasses or interfere with host defenses?
A
Endotracheal tubes
Nasogastric tubes
Respiratory therapy machinery
18
Q
How come older patients have impaired pulmonary defenses?
A
Increased number and severity of underlying diseases
Less effective mucociliary clearance and coughing
Increased microaspiration
Immune senescence
19
Q
What are underlying disease that can impair pulmonary defenses?
A
COPD
Immune deficiencies
Asplenia
Others
20
Q
What causes community-acquired acute pneumonia?
A
1st line: -Strep pneumonia (MOST COMMON) -Legionella Pneumophila -Klebsiella pneumoniae 2nd line: -H. influenzae -Staph aureus -Pseudomonas spp.
21
Q
Bacteria in the mouth are (blank)
A
anearobes (and most are gram neg)
22
Q
What causes community-acquired atypical pneumonia?
A
1st line:
-Mycoplasma pneumonia
2nd line:
-Chlamydia spp. (C. pneumoniae, C. psittaci, C. trachomatis)
23
Q
What causes hospital-acquired pneumoni?
A
1st line: -Klebsiella spp -Legionella pneumophilia 2nd line: -Pseudomonas spp -Staph aureus
24
Q
What causes chronic pneumonia?
A
- nocardia
- Mycobacterium tuberculosis
- Atypical mycobacteria,
- Histoplasma capsulatum
- Coccidioides immitis
- Blastomyces dermatitidis
25
What causes necrotizing pneumonia and lung abscess?
1st line:
Klebsiella pneumoniae
2nd line:
Staph aureus
26
What causes pneumonia in immunocompromised host?
- Pneumocystis jiroveci (associated with AIDS)
| - Mycobacterium avium-intracellulare
27
What is this:
| Exposure to contaminated aerosols, e.g., air coolers, hospital water supply
Legionnaires' disease
28
What is this:
| Exposure to goat hair, raw wool, animal hides
Anthrax
29
What is this:
| Ingestion of unpasteurized milk
Brucellosis
30
What is this:
| Exposure to bat droppings (caving) or dust from soil enriched with bird droppings
Histoplasmosis
31
What is this:
| Exposure to water contaminated with animal urine
Leptospirosis
32
What is this:
| Exposure to rodent droppings, urine, saliva
Hantavirus
33
What is this:
| Potential bioterrorism exposure
Anthrax, plague, tularemia
34
What is this:
| Employment as abattoir work or veterinarian
Brucellosis
35
What is this:
| Exposure to cattle, goats, pigs
Anthrax, brucellosis
36
What is this:
| Exposure to ground squirrels, chipmunks, rabbits, prairie dogs, rats in Africa or southwestern U.S.
Plague
37
What is this:
Hunting or exposure to rabbits, foxes, squirrels
Bites from flies or ticks
Tularemia
38
What is this:
| Exposure to birds
Psittacosis
39
What is this:
| Exposure to infected dogs and cats
Pasteurella mutlocida, Q fever (Coxiella burnetii)
40
What is this:
| Exposure to infected goats, cattle, sheep, domestic animals, and their secretions (milk, amniotic fluid, placenta, feces
Q fever
41
What is this:
| Residence in or travel to San Joaquin Valley, southern California, southwestern Texas, southern Arizona, New Mexico
Coccidioidomycosis
42
What is this:
| Residence in or travel to Mississippi or Ohio river valleys, Caribbean, central America, or Africa
Histoplasmosis, blastomycosis
43
What is this:
| Residence in or travel to China
SARS, avian influenza
44
What is this:
| Residence in or travel to Arabian peninsula
MERS-CoV
45
What is this:
| Residence in or travel to Southeast Asia, West Indies, Australia or Guam
Melioidosis
46
What is this:
- Lung obstructed by viscous secretions
- Persistent bacterial infection produces airway wall damage
What causes this?
Cystic fibrosis
```
Staphylococcus aureus
Pseudomonas aeruginosa
Burkholderia cepacia complex
Haemophilus influenzae
Other bacteria, anaerobes, fungi and viruses
```
47
When you hear the word sickle cell disease what bacteria should you be thinking of?
strep pneumo
48
How should you treat CF?
Remove viscous and purulent airway secretions
Control bacterial infection with antibiotics
Provide proper nutrition for host defense
49
What is the gold standard for making a clinical diagnosis of pneumonia?
Radiology
50
What is the history you should look at for a pnt suspected of having pneumonia?
What are the physical exam findings?
Symptoms consistent with pneumonia
Clinical setting in which pneumonia takes place
Defects in host defense
Possible exposure to specific pathogens
fever, chest exam (not very helpful)
51
What are the diagnostic tests for pneumonia?
- Examination of sputum
- Fiber-optic bronchoscopy
- Examination of pleural effusions
- Blood culture, serology, and urine studies, including antigen detection
- Radiology – gold standard for making a clinical diagnosis
52
A 10-year-old child with a history of sickle cell disease was treated for pneumococcal pneumonia with a standard regimen of ceftriaxone. The treatment failed, and an antibiotic sensitivity test found that the bacterium was resistant to standard doses of penicillins. What is the most likely reason for resistance to penicillin in this isolate.
Production of altered penicillin binding proteins with reduced affinity for amoxicillin
53
What is the primary cause of bacterial pneumonia and meningitis?
Pneumococcal pneumonia (caused by strep pneumo)
54
In whom does pneumococcal pneumonia present in?
Where do you generally find it?
What does the sputum look like?
What are some clinical findings?
- immunocompromised hosts (age, physical condition, genetic i.e sickle cell)
- lower lobes
- bloody rusty sputum
- abrupt onset, fever, sharp pleural pain, bloody rusty sputum
55
How do you treat pneumococcal pneumonia?
Approach varies with site of infection, setting of infection and condition of the patient
56
```
What kind of bacteria is Klebsiella pneumoniae:
Gram pos or gram neg?
naked or encapsulated?
Rod or cocci?
fermenter?
What is it a member of?
```
- gram neg
- encapsulated-antiphagocytic
- lactose fermenting
- rod
- enterobacteriaceae
57
What is the disease the klebsiella pneumoniae cause and what does it do?
What does the sputum look like?
What patients does this present in?
Pneumonia- necrotic destruction of alveolar spaces
(also found in UTI in elderly, wound infection, bacteremia and meningitis)
Thick, bloody, MUCOID, sputum
-Compromised
Immune suppressed or impaired respiratory defenses
58
What samples should you take to check for Klebsiella?
What medium do you use?
What are identifiers?
Samples – sputum, blood, pus, CSF
Isolation – typical enteric medium
Identification
- Fermenter
- Mucoid colonies
- Typical enteric differential media
59
What is Klebsiella a disease of? Who doesnt get this?
How is it spread?
How do you prevent it
Disease of sick people; healthy people rarely develop disease
Spread in hospital setting
- Person to person
- Contamination of ventilators
- IV catheters or wounds
Prevention – strict attention to infection control measures
60
What are the mechanisms that can make K. pneumonia resistant to antibiotics?
- Overproduction of a beta lactamase
- Extended spectrum beta lactamases
- Efflux pump
- Carbapenem resistance
61
Why is carbapenem-resistant Klebsiella Pneumonia (CRKP) the scariest shit ever?!
IT hydrolyzes (destoys) ALL KNOWN beta lactam antiobiotics via its blaKPC gene
- resistant to beta lactam inhibitors
- leaves few or no tx options
- can use polymyxins (target outter membrane of gram - bacteria but are toxic to the body)
62
A 66-year-old male is seen in the emergency room complaining of chest pain of sudden onset, cough productive of purulent and blood-tinged sputum, and fever, which arose abruptly after an initial sharp chill. What is the most likely etiologic agent for this pneumonia?
Strep pneumonia
63
```
What kind of bacteria is Legionella pneumophila:
What's its shape?
Gram pos or gram neg?
Rod or cocci?
What does it need to survive?
What is its resistance mechanism?
How many species infect humans?
```
```
thin, pleomorphic
gram negative
rod
Needs cystein and iron (a fastidious i.e needy bacteria)
Prevents phagolysosome fusion
20
```
64
What does Legionnaries disease cause?
What are some symptoms of this?
Is it a fatal disease?
Disease
-severe, acute pneumonia
Symptoms
-Fever, non-productive cough, SOB, myalgias
Yes, 15-20% mortality
65
What are the risk factors for Legionnaire's disease caused by Legionella?
Risk factors
- Age 50 years or older
- Current or former smokers
- Chronic lung disease (COPD or emphysema)
- Weakened immune system
* ***diabetes, kidney failure, immunosuppression
66
What is this
Mild form of respiratory infection – no pneumonia
Follows exposure to aerosol; high attack rate
Pathogenesis not understood
Self-limiting; very low mortality, <1%
Pontiac fever caused by Legionnaires disease
67
What is the pathogenesis of Legionnaires' disease?
- inhale infectious aerosol
- infects alveolar macrophages, monocytes and alveolar epithelial cells
- inhibition of phagolysosomal fusion
- intracellular proliferation
- inflammatory response
- eventually, cell-mediated immunity
68
What do macrolides do?
protein synthesis on 50S
69
Why is inhibition of phagloysosomal fusion a defense mechanism for legionella?
Inhibition of phagolysosomal fusion prevents exposure to superoxide, H2O2 and OH radicals
70
How do you diagnosis Legionnaires disease?
| How do you get a specimen?
X-ray or physical exam, microscope, culture, URINARY ANTIGEN TEST, direct flourescence antibody, nucleic acid amplification assay
-use sputum or endotracheal aspirate and put on special medium (cystine and iron)
71
What is the most common diagnostic tool for diagnosis of Legionnaire's disease?
What does each serotype 1 tell you?
Urinary antigen test (most commonly used diagnostic tool)
- Detects serogroup 1 LPS
- Serogroup 1 – 80-90% of community acquired infections
- Serogroup 1 - < 50% of hospital-acquired infections
72
Where is legionella found? and how do you get it?
| Is it common?
Found in aqueous environments (likes warm water
Acquired by exposure to contaminated aerosols-AC, cooling towers, hot tubs, water misters. etc.
common (20,000-100,000 a year)
73
What did serological testing of legionella show? Why can you find it a lot in hospitals?
Serological testing indicates subclinical infection is very common
-due to number of high-risk patients
74
WHy dont you do susceptibility tests for legionnaires disease?
What antibiotics do you treat Legionnaire's with?
due to difficulty growing bacterium
Macrolides
- AZITHROMYCIN
- clarithromycin
Fluoroquinolones
- LEVOFLOXACIN
- moxifloxacin
Tetracycline
-Doxycycline
75
How do you treat pontiac fever?
Pontiac fever requires no treatment
76
An 85-year-old male nursing home patient with a history of alcoholism suddenly developed a flu-like illness. He complained of chills and fever and had frequent coughing spells of productive, thick, bloody sputum. The attending physician diagnosed bronchopneumonia and prescribed antibiotics, but regrettably, the patient died within a week. A gram-negative rod was isolated on MacConkey agar. What is the primary function of the pathogenicity determinant depicted in this photo?
Can see the capsule that he is pulling up. This is klebsiella and the capsule is antiphagocytic
77
What is the smallest free-living bacterium?
Does it have a cell wall?
What does it cell membrane look like?
How do you grow this?
Mycoplasma pneumoniae
nope so resistant to beta lactams (carbapenems, cephalosporins), and vancomycin
Contains sterols obtained from host e.g cholesterol
in medium with sterols
78
What is the MOA of azoles?
inhibit synthesis of ergosterol
79
What is the pathogenesis of mycoplasma pneumoniae?
adheres to respiratory epithelium via P1 protein adhesin and receptors on host cell-> destroys cilia and ciliated epithelial cells-> irritation and secondary infection cause persistent cough
80
Most infections of mycoplasma pneumoniae are (blank). What is the most common infection and how does it present?
What else does it cause and how does it present?
asymptomatic
tracheobronchitis- low grade fever, malaise, headache, non-productive cough
Primary atypical pneumonia-not terribly ill "walking pneumonia" with patchy bronchopneumonia on chest radiograph (more impressive than acutal clinical signs)
81
How do you diagnosis mycoplasma pneumoniae?
empirically on basis of clinical signs
| dont use microscope or cultures, or nucleic acid amp or serology -all lack sensitivity
82
Why dont you want to use culture for mycoplasma pneumoniae?
- Requires special media supplemented with serum (sterols)
- Slow grower – takes 2-6 weeks to result
- Most clinical labs not set up to do culture
83
Why dont you want to use serology for mycoplasma pneumoniae?
Complement fixation – lacks sensitivity and specificity
Cold agglutinin
-IgM antibodies that bind and cross react with I blood group antigen on human erythrocytes at 4ºC
-Lacks sensitivity and specificity; no longer recommended
84
In mycoplasma pneumoniae:
Strictly a (blank) pathogen; spread via (blank)
(blank) cases and 100,000 hospitalizations/year in U.S.
Worldwide with no seasonal incidence
Primarily infects children between ages (blank) years, but all populations susceptible
human
respiratory droplets
2,000,000
5-15
85
How do you treat mycoplasma pneumoniae?
Macrolide
- erythromycin
- azithromycin Tetracycline
- doxycycline Fluoroquinolone
*** NOTE: Each antibiotic has considerations
Cost - fluoroquinolones are expensive; tetracyclines are cheap
Age - no use of tetracyclines in children
86
The patient is a 72-year-old man who was hospitalized for complications of COPD. The patient developed headache, myalgia, chills and high fever. Two days later, the patient developed a cough, chest pain and shortness of breath. Legionnaire’s disease was suspected. Which of the following tests could be used to confirm a diagnosis of Legionnaire’s disease?
Presence of Legionella pneumophila antigen in urine
87
What are the 5 endemic dimorphic fungi that cause pneumonia?
- Histoplasmosis
- Blastomycosis
- Coccidiomycosis
- Paracoccidiodes brasiliensis
- Penicillium marneffi
88
What are the 2 types of histoplasmosis?
- Histoplasma capsulatum var. capsulatum
| - Histoplasma capsulatum var. duboisii
89
What are the 2 types of coccidiomycosis?
Coccidioides immitis
| Coccidioides posadasii
90
Where do you only find endemic h. capsulatum?
Where will you only find endemic penicillum marneffi?
Where do you find endemic blastomyces dermatitidis/histoplasma capsulatum?
Where do you find endemic paracoccidiodes barsiliensis/H capsulatum?
Where do you find endemic H. capsulatum var duboisii?
Where do you find endemic coccidioides immitis?
Brazil
Southeast Asia
East US
Mexico and south america (columbia etc)
Africa
Southern part of N. America
91
What does histoplasma capsulatum look like in the tissue phase?
In the saprobic phase?
- Intracellular budding yeast
| - tuberculate macroconidia
92
What does blastomyces dermatitidis look like in the tissue phase? In the saprobic phase?
Tissue - broad-based yeast
| Saprobic phase - nondescript mycelium
93
What does paracoccioides brasiliensis look like in the tissue phase? In the saprobic phase?
Tissue – large, multiply budding yeast
| Saprobic phase - nondescript mold
94
What does Coccidioides immitis look like in the tissue phase? in the saprobic phase?
Tissue – Endosporulating spherule
Saprobic phase – arthroconidia
95
What does Penicillum marneffei look like in the tissue phase? In the saprobic phase?
Tissue – sausage-shaped yeast
Saprobic phase – pigmented mold
96
What is this:
| inhabits soil with high nitrogen content. e.g. bird and bat droppings
Histoplasma capsulatum
97
What geographic location will you find Histoplasma capsulatum
```
H. capsulatum var. capsulatum
-N. America- Ohio and Mississippi River valleys
-Mexico, Central and S. America
H. capsulatum var. duboisii
-tropical areas of Africa
```
98
What is the major risk factor for Histoplasma capsulatum var. capsulatum?
AIDs!!!!!!!
99
What is the natural history (growth plan) of Histoplasma capsulatum?
Inhalation of microconidia-> Germination into yeasts-> Intracellular growth in lungs
100
T or F
| Histoplasma capsulatum can remain localized or disseminate
T
101
What is the primary host defense of Histoplamosis?
Cellular immunity
102
Acute pulmonary histoplasmosis is common in (blank) areas.
greater (blank) percent are asymptomatic or have (blank) symptoms.
What other 2 symptoms do they have?
endemic areas
90%
flu-like (fever, headache, chills)
-nonproductive cough and chest pain
103
How does chronic pulmonary histoplasmosis present?
fever, productive cough, chest pain, cavitary lesions (in most cases)
104
What is progressive disseminated histoplasmosis and how common is it? what are the risk factors of it?
- multiple organ systems, occurs in 1/2000 cases of histoplasmosis
- over 55 years or immunosuppression
105
What causes African histopasmosis? How common is it?
H. capsulatum var. duboisii
| -it is the most common: skin and skeletal involvement
106
What is the histopathology of histoplasmosis?
small budding yeasts within macrophages
107
What is the dimporphism of histoplasmosis dependent on?
temperature
108
What are the 2 ways that histoplasmosis presents itseld?
```
As mycelium (mold)-tuberculate macroconidia below 30 C
As Yeast at 37 C or in tissues (small, oval budding yeasts)
```
109
What will an antigen immunoassay on histoplasmosis show? What is the best sample to obtain for this?
- detects cell wall polysaccharide
| - urine
110
What wil serology test for in histoplasmosis?
(blank) percent of normals are positive in endemic areas.
(blank) percent of patients with acute histoplasmosis develop antibody.
Serum antibodys and
Complement fixation or precipitation
10%
75%
111
What will a histoplasmin skin test determine and what is it useful for? what isnt it useful?
delayed hypersensitivity
| epidemiology; little value for diagnosis
112
How do you treat histoplasmosis?
- most cases no tx
- antifungals
* Itraconazole, (flucanozole is much less effective)
* amphotericin B or liposomal amphotericin B
113
A 23-year-old man was seen after 2 weeks of cough with left-sided chest pain and fever. Physical examination revealed blood pressure of 142/78 mm Hg, respiratory rate 32/min, temperature 37.5°C, and dullness and decreased breath sounds over the left lower chest. A diagnosis of primary atypical pneumonia was made. What is the best antibiotic for treatment?
A macrolide such as azithromycin
114
Where do you find blastomyces dermatitidiz?
inhabits soil containing decaying organic matter
115
What is the geographic distrubtion of blastomyces dermatitidis?
Ohio and Mississippi River Valleys
Southeastern U.S
Endemic areas overlap with histoplasmosis
116
What is the natural history of blastomyces dermatitidis?
- inhalation of conidia from environmental sites
- germination into yeasts
- growth in lungs
- may remain localized or disseminate
117
(blank) are highly susceptible to blastomyces dermatitidis but not a reservoir
Dogs
118
What is the primary host defense of blastomycosis?
cellular immunity
119
acute pulmonary blastomycosis has (blank) percent being asymptomatic. May progress to fulminant (blank) with abrupt onset of (blank x 4)
50%
respiratory disease
myalgias, arthralgias, chills, and fever
120
In the disseminated disease of blastomycosis, what organ is most often involved?
It may involve multiple sites which are...?
skin
| -lymph nodes, bones and joints, prostate, CNS
121
Blastomycosis occurs in (blank) patients but less often than other endemic fungi, BUT when it does occur it takes an (blank) course
immunocompromised patients
| aggressive
122
What is the histopathology of blastomycosis?
-broad-based, large, budding yeasts
123
Blastomycosis exhibits (blank) dimporphism. When it is not in tissues or warm it grows as a (blank). When it is in the body or above 37 C then it grows as (blank). How do you confirm this?
temperature-regulated dimorphism
mycelium (non-specific morphology)
Yeast (small, oval, broad-based budding yeasts)
PCR
124
What will the antigen immunoassay of urine detect about blastomycosis? Why isnt this a good test?
```
Detects cell wall polysaccharide (refernce lab only)
Low specificity (cross-reactive w. other endemic fungi)
```
125
WHat tests are USELESS in blastomycosis?
serology and skin tests
126
What is the treatment of blastomycosis?
- Itraconazole (for mild or moderate)
| - lipid formulation of amphotericin B (severe disease, disease in immunocompromised patient)
127
A 13-month-old boy in severe respiratory distress was brought to the emergency department following a 3-day history of worsening cough and audible wheezing. The patient was tachycardic and lethargic and had a low-grade fever of 38.1°C. A chest X-ray revealed right upper and lower lobe opacities. Also of note, the patient had returned from a 3-month visit to Pakistan with his family 4 months prior to presentation in the ED. Respiratory secretions obtained by tracheal suction grew carbapenem-resistant Klebsiella pneumoniae. What is the mechanism for carbapenem resistance in this bacterium?
Production of a broad spectrum beta lactamase
128
What is coccidioides immitis like in nature? in tissues?
nature-> mycelium with "barrel shaped" arthroconidia in soil
Endosporulating spherules in tissues
tissues-> endosporulating spherules
129
Where do you find coccidioides immitis?
in the soil of dry, low-rainfall areas
130
What is the geographic distribution of coccidioides immitis?
-Southwestern U.S (regions of california, arizona, and new mexico), Mexico, Central and South America
131
What are the 2 indistinguishable species of cocciodioides immits and where are each found?
C. immitis – California
| C. posadasii – all Infections outside California
132
What is the natural history of Coccidioides immitis?
Inhalation of arthroconidia
Germination in lungs and formation of spherules
May remain localized or disseminate
133
What is the fever associated with coccioidomycosis?
valley fever
134
Primary pulmonary coccidioidomycosis infects (blank) percent of individuals in endemic areas.
You get symptoms (blank) days after exposure.
What are the symptoms?
30-60%
7-21 days
-cough, chest pain, SOB, fever, fatigue
135
Coccidiomycosis can cause pulmonary nodules and cavities in (Blank) percent of pulmonary infections.
What are the symptoms of this?
4%
| -pleuritic pain, cough, hemoptysis
136
Coccidiomycosis can cause extrapulmonary dissemination which occurs in (blank) percent of pulmonary infections. What are the risk factors? What is the most serious form?
- 0.5%
- immunosuppression, genetic (african or fillipino)
- Coccidioidal meningitis
137
What are the three major diseases that coccidioidomycosis can cause?
- Primary pulmonary coccidioidomycosis
- Pulmonary nodules and cavities
- Extrapulmonary dissemination
138
What is the histopathology of coccidioidomycosis? What will this tell us?
- endosporulating spherules in sputum, exudates or tissue
| - it establishes diagnosis
139
Should you culture coccidioidomycosis and why?
| What is the shape of coccidioidomycosis?
no-biohazard
Mycelium-arthoconidia
140
Should you use serology to detect coccidiomycosis? Who should you use it in?
(blank) % of normals are positive in endemic areas
(blank) % of patients with acute coccidiomycosis develop antibody
yes
-pnts w/non-productive cough
(Complement fixation or precipitation)
10%
75%
141
What will a coccidioidin skin test show? whats it useful for? Is it useful for a diagnosis?
delayed hypersensitivity
epidemiology
no
142
How do you treat coccidioidomycosis?
- Oral azole: fluconazole, itraconazole, or ketoconazole
| - Amphotericin B
143
An outbreak of coccidioidomycosis occurred in the Avenal and Pleasant Valley prisons in the California Central Valley, with 16 recent deaths in a period of a few months. As Medical Director for the California Prison System, what would you recommend to prevent serious illness and death?
transfer all high-risk inmates to other sites
144
Pneumocystis is classified as a fungus based on (blank) sequence
rRNA
145
What does pneumocystic lack even though its a fungus?
ergosterol
146
What are the species of pneumocystis?
Can you in vitro culture them?
Pneumocystis jirovecii-human
Pneumocystis carinii-rat
NO!
147
The life cycle of (blank) has sexual and asexual components
pneumocystis
148
(blank) microbial forms of pneumocystic are found during human infection. What are these?
All
- free trophic forms
- sporozite (precystic) form
- cysts with up to 8 intracystic bodies (spore)
149
(blank) is very specific species for very specific hosts.
Pneumocystis
| so this is dumb to try and grow it in a rat since it will be a completely different strain that a human
150
What is the resistance like in pneumocystis?
natural resistance is high
151
How do people get pneumocystis?
if they are compromised, it allows organisms to proliferate and gradually fill alveolar lumens
152
How can you recognize pneumoncystis?
foamy exudate in alveolar space w/ intense interstitial infiltrate of plasma cells
153
What will pneumocystis progress to?
interstitial fibrosis and edema
154
Pneumocystis will cause (blank) in debilitated infants (classic presentation)
Interstitial plasma cell pneumonitis
155
What are the symptoms of Pneumocystis pneumonia in immunosuppressed pnts?
-SOB, fever, nonproductive cough
156
What are the symptoms of Pneumocystis pneumonia in HIV pnts?
-SOB, fever, nonproductive, cough (same as immunosuppressed but more subtle)
157
What are the symptoms of Pneumocystis pneumonia in infants?
insidious onset, respiratory distress, and cyanosis
158
What is the rate of mortality in Pneumocystis pneumonia? What causes the mortality?
- high mortality if untreated
| - death due to respiratory failure
159
(blank) is the number one global cause of immunosuppression so kids in orphanges get it a lot.
malnutrition
| so these kids got Interstitial Plasma Cell Pneumonitis
160
How do you diagnose pneumocystis pneumonia?
empiric-clinical signs in immunosuppressed patients
| Microscopy MOST useful
161
If using microscopy to diagnose pneumocystis, what stains do you want to use?
- BAL fluid (use bronchial brushing, induced sputum) HIGHLY sensitive
- Wright-Giemsa stains all forms
- Silver stains for cyst
162
What does pneumocystis look like with a Gomori silver stain?
crushed ping pong ball appearance (due to cysts)
163
Pneumocystis has ubiquitous colonization early in life, within first (blank) years
2
164
How is pneumocystis spread?
communicable via airborne route
165
(blank) allows for reactivation of latent infection or progression of recently acquired infection in pneumocystis.
Immunocompromise
166
What are the risk categories for getting pneumocystis pneumonia?
- malnourished or premature infants, SCID, hyper IgM syndrome
- Immunosuppressive medications
- AIDs
167
Once the most common opportunistic infection in AIDs; less frequent with HAART> What am I talking about?
pneumocystic pneumonia
| 2nd most opportunistic infection caused by fungi behind cryptococcus
168
How do you treat pneumocystic pneumonia?
-Trimethoprim-sulfamethoxazone for prophylaxis and tx
169
If you patient has pneumocystic pneumonia and AIDs, what CD4 levels will indicate the need for chemoprophylaxis?
chemoprophylaxis for AIDS with CD4 counts <200/mm3
170
What does trimethoprim-sulfamethoxazone do?
inhibits folate acid synthesis and are synergistic
171
The patient is a 14-year-old female who developed fever, malaise, headache, and cough. The frequency and severity of cough increase over the next 1 to 2 days and became debilitating. The patient developed parasternal chest soreness due to muscle strain and sought medical attention. Examination of the chest was unrevealing. A diagnosis of mycoplasma pneumonia was made on the basis of clinical signs. What is the cause of the severe cough that is produced by this bacterium?
Microbial destruction of cilia and ciliated epithelial cells
| Makes the pnts more susceptible to other infections as well
172
What bacteria produces toxicity due to an M protein on the bacterial surface?
Group A strep (strep pyogenes)
173
What bacteria produces a tracheal cytotoxin?
Bordatella pertussis
174
The patient is a homeless 24-year-old male who presents with shortness of breath, fever and a non-productive cough. The patient was diagnosed with AIDS on the basis of CD4 counts and viral load. Examination of induced sputum showed cysts suggestive of Pneumocystis infection. What is the initial source of infection by Pneumocystis jirovecii?
an infected human
175
Is mycobacteria gram positive or gram negative? Is it a rod or cone? spore forming or non-spore forming? Aerobic or anaerobic?
- non-spore forming
- weakly gram pos
- acid-fast rods
- highly aerobic
176
What does mycobacteria have in the cell walls? What properties does this allow the bacteria to have?
mycolic acid -> long fatty acids
- acid-fastness
- resistance to gram staining
- resistance to detergents, hydrophobic antibiotics, survival in macrophages
- "cording" arrangment of cells
177
What is the structure of the cell wall like in mycobacteria?
Somewhat like gram-positives; inner membrane, thick peptidoglycan layer, no outer membrane
178
(blank) is a glycolipid, and a virulence factor associated with Mycobacterium tuberculosis, the bacteria responsible for tuberculosis. Its primary function is to inactivate (blank and blank)
- Lipoarabinomannan, also called LAM
| - macrophages and scavenge oxidative radicals
179
60% of the cell wall weight of mycobacteria is (blank) and also has some (blank)
```
lipids
Lipoarabinomannan (LAM): functionally similiar to O-antigens
```
180
What are the only 2 spore forming bacteria?
Clostridium and anthrax
181
What causes tuberculosis?
M. tuberculosis complex
182
How do humans get mycobacterium bovis?
its in cattle and spread to humans by eating or drinking contaminated dairy products
183
What is a less virulent strain of M. bovis?
Bacille (bacillus) Calmette-Guerin
184
What is a major cause of tuberculosis in Africa?
M. africanum and M. canetti
185
(blank) is an atypical mycobacteria?
non-tuberculosis
186
Mycobacterium (blank) is unusual and you cant grow it
leprae
187
(blank), or trehalose dimycolate, is a glycolipid molecule found in the cell wall of Mycobacterium tuberculosis
Cord factor
188
What is Trehalose dimycolate made up of?
- glycolipid cell wall component of virulent strains
| - subset of cell wall mycolic acids
189
What does trehalose dimycolate (cord factor) do?
it binds to a macrophage surface receptor called mincle
190
What is the macrophage surface receptor that trehalose dimycolate (cord factor) binds to in mycobacterium?
mincle
191
What does mincle do?
- blocks macrophage activation by IFN-gamma
- induces secretion of TNF-a
- causes formation of cords
192
What does mycobacterium tuberculosis need to do to survive?
it needs to get inside macrophages without dying
193
How does mycobacterium tuberculosis get inside macrophages without dying?
it gets phagocytized by alveolar macrophages and survives by preventing fusion of phagosome with lysosome (i.e. so lysosomes toxic secretions cant attack it)
194
If a mycobacterium TB is latent in a macrophage and then you get activation, what will be the DTH response?
Infected macrophages secrete cytokines (IL-12 and TNF-a)-> T cells-> TH1 secrete IFN-gamma-> IFN-gamma activates infected macrophages-> phagosome lysosome fusion and killing by reactive oxygen and nitrogen species
195
What will the DTH reaction associated with TB cause?
may lead to granuloma (lymphocyte, macrophages, epithelioid cells, fibroblasts and giant cells)
196
How do you get resolution of the DTH response in TB?
kill bacteria or if it goes dormant
197
How can you get reactivation of TB? It will results in (blank) response
- waning or loss of cellular immunity allows for outgrowth of bacteria
- destructive
198
How does primary TB typically present?
| What may it progress to?
- most often asymptomatic or mild fever and malaise
| - reactivation or dissemination
199
What do the radiographs show in primary TB?
mid-lung infiltrates and hilar lymphadenopatthy
200
(blank) percent of individuals with primary TB reactivate.
| Who does it typically present in? What is it typically associated with?
10%
men over 50
immunosuppression-AIDs most common
201
What are the symptoms of reactivation TB?
-dry cough that becomes productive and mixed with blood (hemoptysis)
202
What will the lung apices look like in mycobacterium TB?
filled with cavities and huge numbers of bacteria
203
If mycobacterium TB isnt treated, what is the prognosis? When is the course more rapid?
2-5 yrs
| AIDs or other T cell compromise
204
Where can you get mycobacterium infections?
ANY ORGANS (doesnt just stick to lungs)
205
How do you diagnose mycobacterium TB?
- H and P
- Clinical signs
- Radiology (allows presumptive diagnosis)
206
Why is radiology central to the diagnosis of mycobacterium TB? What finding is highly suggestive of TB?
determine extent, character, and therapy
-Patchy or nodular infiltrate in the lung apices, especilly if infiltrate is cavitary
207
How do you immunodiagnose TB?
What are a three other tests you can do?
skin testing
IFN gamma release assay
Nucleic acid based tests
Microscopy-acid fast staining
Culture
208
How do you do a tuberculin skin test?
- intradermal injection of 5 tuberculin units of PPD (protein-part of cell wall)
- read at 48-72 h for induration (not erythema)
209
Reading a TB test:
(blank) mm is the cut-off for immunosuppressed or recent contacts
(blank) mm is the cut off for other high-risk groups
(blank) mm is the cut-off for low risk groups
5 mm
10 mm
15 mm
210
What will a positive tuberculin skin test show?
infection, not necessarily disease
211
False-positives for TB is caused by infection with (blank)
non-Mtb mycobacteria
212
When will you get false negatives for TB? How can you double check?
- Generalized illness or immunosuppression
- additional skin tests with candida or mumps antigens can identify anergy but are not generally recommended for negative tests
213
How does the IFN-gamma release assay work?
- take whole blood incubated with Mtb antigens
- measures release of IFN-gamma
- three Mtb protein antigens should be found
214
What are the advantages to doing a IFN gamma release assay?
No reaction with people who received BCG
No need to return to have skin test evaluated
No booster effect with repeated testing
215
What are the disadvantages of IFN-gamma release assay?
What does the CDC recommend?
- much more expensive
- requires laboratory infrastructure
-to use it to detect Mt infection and for surveillance
216
A 27-year-old man from southern Mexico with newly diagnosed AIDS presents to the clinic with 4 weeks of fever, chills, night sweats, myalgias, dry cough, nausea, vomiting, and diarrhea. He recently had a negative tuberculin skin test. He is initially treated for presumptive Pneumocystis pneumonia and atypical pneumonia. Two weeks later, however, fungal blood cultures show growth of hyphal elements shown in the figure below. What is the diagnosis?
Disseminated histoplasmosis
217
What is the gold standard for finding mycobacterium TB?
culture (detects 10-100 Mtb/ml)
218
How do you culture mycobacterium TB?
samples from contaminates sites must be decontaminated (mycobacteria will survive this)
-->Use colony morphology and biochemical tests and species-specific molecular probes
219
What is the culture medium that Mycobacterium TB needs to grow on?
Solid-Lowenstein-Jensen or Middlebrook (3-8 wks)
| Liquid- 1-3 weeks
220
How do you identify mycobacterium TB on a culture?
- colony morphology
- biochemical tests
- species-specific molecular probes
221
What will an agar proportion tell you?
What is a liquid broth system good for?
What will molecular tests tell you?
- percentage of resistant Mtb
- rapid results
- detects resistance to rifampin
222
How many people does TB infect?
1/3 worlds pop
- 9 million new cases and 2 million deaths anually
- TB in US (11,000 new cases/year, most are foreign born, reactivation disease)
223
How does mycobacterium TB spread?
humans are only natural reservoir
| person-to-person spread via airborne droplet
224
What are the risk factors for mycobacterium TB?
- Most infections dealth with by the immune system
- Exposure (closeness of contact (i.e healthcare workers, institutional exposure) infectiousness of source e.g cavitary tuberculosis)
- Immune suppression
225
What is the tx for TB?
Antibiotics – first-line drugs used in combination
- Isoniazid (INH) – inhibits synthesis of mycolic acid
- Rifampin (RMP) – inhibits DNA-dependent RNA polymerase
- Ethambutol (EMB) – inhibits cell wall synthesis
- Pyrazinamide (PZA) – mechanism not well understood
226
What does this:
| inhibits synthesis of mycolic acid?
isoniazid (INH)
227
What does this:
| inhibits DNA-dependent RNA polymerase
Rifampin
228
What does this:
| inhibits cell wall synthesis
Ethambutol (EMB)
229
What does this:
| mechanism not well understood
Pyrazinamide
230
What are some other agents that can treat Tuberculosis?
Aminoglycosides
| Fluoroquinolones
231
What are the tx strategies for TB?
1) use of multiple drugs (4); (combats emergence of resistance)
2) Directly observed tx (DOT)3)
Consult current guidelines
232
What causes multidrug resistant Mtb (MDR TB) and what is it resistant to?
- Resistant to at least isoniazid and rifampin
| - course of antibiotics is interrupted, levels of drug insufficient to kill 100% of bacteria
233
What is extensively drug-resistant Mtb (XDR TB)? How does it start? What region is this found? Is it treatable?
- resistant to isoniazid + rifampin + quinolones + at least one second-line drug
- starts as MDR TB
- now in most regions of the world
- potentially untreatable
234
What is a less virulent strain of M. bovis?
BCG vaccine
235
Is BCG vaccine a live one?
Who is given this?
Has it helped?
yes
infants immunized with live bacterium in endemic countries
-yes, reduced incidence of disseminated TB in children
(not widely used in US or other countries with low incidence of TB)
236
Incidence of disseminated TB is (blank) in children
low
237
What will the BCG vaccine do to the TB skin test?
produces false-positive skin test; but skin test reactivity is low
238
Does BCG consistenty reduce incidence of adult pulmonary disease?
NO!
239
Whats sort of scary about the BCG vaccine?
May produce BCG disease in patients with primary or acquired immune deficiency e.g. AIDs
240
Will AIDs patients have delayed type hypersensitivity reactions?
If an AIDS patient has TB will their test turn up positive?
No they wont
| Only if their CD4 count is high enough to make a DTH reaction.
241
How is atypical mycobacteria (non-tuberculous mycobacteria NTM) classified?
basis of growth rate and pigmentation (Runyon)
242
What are the major disease-producing species (total>50) of non-tuberculous mycobacteria (NTM)?
```
M. kansasii
M. fortuitum
M. abscessum
M. ulcerans
M. marinum
```
243
How do you get non-tuberculous mycobacteria (NTM) ie. atypical mycobacteria?
acquired from environmental sources e.g. tap water
244
What are the disease/syndromes associated with non-tuberculous mycobacteria (NTM)?
- chronic bronchopulmonary disease
- skin and soft tissue disease
- lymphadenitis
- disseminated disease in immunosuppressed patient (e.g. AIDS)
245
(blank) is ubiquitous in the environment and is the most antibiotic-resistant and virulent of the NTM
M. abscessum
246
What are the resistance mechanisms of NTM?
- antibiotic modifying (aminoglycosides)
- degrading enzymes (beta lactams)
- target modification (macrolides)
- efflux pumps
247
What is the Tx for NTM?
```
surgical intervention (drain lesions)
antiobiotics
```
248
What are the 2 major species of Mycobacterium avium complex (MAC)?
M. avium and M. intracellulare
249
What are the diseases associated with MAC?
- primary infection (no reactivtion disease)
- chronic localized pulmonary disease
- Disseminated disease in advanced AIDS
- Cervical lymphadenitis
250
Who gets chronic localized pulmonary disease caused by mycobacterium avium complex (MAC)?
patients with intact immunity Risk factors:
| smoking and COPD
251
Who gets disseminated disease from mycobacterium avium complex (MAC)?
AIDS patients with CD4+ <100
| very common prior to HAART
252
What are the ways you can diagnose MAC?
- microscopy (generally lacks sensitivtiy and specificity)
- culture
- blood culture for disseminated disease
253
How do you acquire MAC?
- from environmental sources (no human-human spread)
- inhalation or ingestions
- natural water sources. indoor water systems, pools, hot tubs
254
How do you treat MAC?
very difficult to treat (high failure rate)
- clarithromycin or azithromycin + ethambutol and rifampin
- Azithromycin prophylaxis if CD4 < 50 cells/mm2
255
Is nocardia gram positive or gram negative? Is it acid fast? is it a rod or cone? is it aerobic or anearobic?
gram positive
weakly acid fast
filamentous rod
aerobic
256
What are the species of nocardia?
N. asteroides
N. brasiliensis
Rhodococcus (uncommon)
Gordonia (rare; opportunistic infections)
Tsukamurella (rare; opportunistic infections)
257
What does Rhodococcus affect?
pulmonary, cutaneous, CNS disease
258
What are the virulence factors of Nocardia?
Avoids intracellular killing
- catalase and superoxide dismutase inactivate toxic metabolites
- cord factor
259
What does cord factor do?
- prevents intracellular killing
| - prevents phagosome-lysosome fusion
260
What does nocardia do to the lungs? Who is it seen in? Where does it disseminate?
- causes bronchpulmonary disease
- immunocompromised patients
- to CNS or skin
261
What are the 4 cutaneous infections that nocardiosis causes?
- mycetoma
- lymphocutaneous infection
- cellulitis
- subcutaneous abscesses
262
What is this:
| chronic granulomatous destruction of extremities
mycetoma
263
How can you diagnose nocardiosis?
- sputum samples (abscess fluid, etc)
- acid-fast stain (distinguishes nocardia from actinomyces)
- culture (requires special media, notify lab)
264
How can you identify nocardiosis?
- filamentous, weakly acid-fast bacilli
- aerial hyphae on agar surface
- molecular analysis: sequencing of rRNA
265
If you see sulfur granules, what is the bacteria?
actinomyces
266
Where do you find nocardiosis?
| Who is this disease most common in?
- ubiquitous in soil rich in organic matter
- incoluation of skin or inhalation
-immunocompromised patient
267
What is the treatment of nocardiosis?
antibiotics
- trimethoprim-sulfamethoxazole (primary antibiotic)
- amikacin, imipenem, broad spectrum cephalosporins used in combo with TMP-SMX in immunocompromised patient
- surgical managment depending on site and extent of infection
268
How long do you treat nocardiosis with antibiotics?
up to 12 months
269
The patient is a 55-year-old man with productive cough, low grade fever, hemoptysis, weight loss, and pleuritic chest pain. Radiology showed lobar alveolar infiltrates without cavitation. Cytology of bronchial washings showed large yeast cells with single, broad-based buds (shown right). Culture of the washing grew mycelia at room temperature that converted to yeast cells when grown at 37ºC. What is the cause of the infection?
Blastomyces dermatitidis
| remember to ask where have you been
270
The patient is a 42-year-old male who is about to undergo treatment with Remicade (Inflixmab, a TNF-α inhibitor) for treatment of rheumatoid arthritis. Prior to initiation of therapy, the patient was given a tuberculin skin test to assess possible risk for tuberculosis. What is the correct interpretation of a positive PPD?
Infection by M. tuberculosis
271
The patient is a 23-year-old female who received cytotoxic drugs in the course of treatment for cancer. She developed shortness of breath and rapidly progressed to respiratory failure. Pneumocystis pneumonia is on the differential diagnosis. What would be the best test to establish an infection of Pneumocystis pneumonia?
Gomori silver stain of induced sputum
