30 - Bacterial Infections of the Lower Respiratory Tract III Flashcards
1
Q
There are two different types of mycobacteria. What are they?
A
Tuberculosis and non-tuberculosis types
2
Q
What type of mycobacteria causes tuberculosis?
A
Mycobacterium tuberculosis
3
Q
What types of mycobacteria do NOT cause tuberculosis?
A
Nontuberculous Mycobacteria:
- Mycobacterium avium-intracellulare complex
- Mycobacterium leprae
- Mycobacterium kansasii
4
Q
What type of bacteria are mycobacteria?
A
Weakly gram positive, acid-fast rods
5
Q
What is another distinguishing feature of mycobacteria?
A
They have a lipid rich cell wall (60% of the wall weight)
This is responsible for the acid-fast staining)
6
Q
What stains can you use in the acid fast test?
A
Ziehl-Neelsen or Kinyoun stains
7
Q
What does a positive acid fast stain tell you?
A
It confirms that there is mycobacteria in the sample, but it does NOT confirm that it is mycobacteria TB
8
Q
What are the seven components of the mycobacteria tuberculosis (Mtb) cell wall?
A
1 - Membrane 2 - Peptidoglycan 3 - Arabinogalactan 4 - Lipoarabinomannin 5 - Plasma membrane andCell wall associated protein 6 - Mycolic Acids 7 - Mycolic acid-associated glycolipids
9
Q
How many people are estimated to be infected with Mtb?
A
- 1/3 of the world’s populations
- 2 billion people
10
Q
What percentage of those infected are active TB?
A
Only 10%, but the 90% with latent TB have a 10% chance of reactivation
11
Q
What is the number one disease burden in the world?
A
Mtb
12
Q
What species can become infected with Mtb?
A
ONLY HUMANS
13
Q
How is Mtb transmitted?
A
- Person to person transmission via respiratory aerosol droplets
Examples: Coughs, sneezes, speaking, singing…
14
Q
What are the four disease states of TB?
A
1 - Primary TB
2 - Active TB
3 - Latent TB
4 - Reactivation
15
Q
What is the disease mechanism of Mtb?
A
- Mtb is inhaled
- Enters the lung alveoli
- Bacilli are taken up into alveolar macrophages
- Lymphocytes are recruited to infection site
- The body forms a multinucleated giant cell around the tubercle baccilus
- A wall of cells and fibrous materials forms around the giant cell to protect surrounding tissues
16
Q
What is the large structure with tubercle baccilus in the center?
A
A “tubercle”
Hence, tuberculosis
17
Q
What is a latent TB infection?
A
Inability of immune system to kill Mtb
18
Q
What will remain in the body during a latent infection?
A
- CD4+, CD8+ and NK cells surround necrotic mass of Mtb infected macrophage
19
Q
Why does it remain latent and not spread?
A
Granuloma prevents further spread or other parts of the body – immune system has controlled it
20
Q
Is primary TB typically bad or not too bad?
A
Primary TB is usually asymptomatic
21
Q
What are the three things that primary TB can directly lead to?
A
1 - Clearance
2 - Active TB
3 - Latent TB
22
Q
Which is the most common?
A
Latent TB
23
Q
When does active TB typically happen?
A
When the individual is already immunocomprimised
24
Q
When does reactivation typically happen?
A
When a healthy individual undergoes a period of becoming immunocomprimised
25
Why are some individuals able to clear the primary disease?
Not sure - it is not well understood
26
Why do we say that cell-mediated (innate) immunity is a "double edged sword" in the case of TB?
- CMI is able to control the TB infection in most cases and sent the patient into an asymptomatic latent TB state
- BUT... Most of the pathology of the disease is a direct consequence of the CMI response
27
How does the CMI contribute to pathology of TB?
When Mtb is rapidly dividing, it increases CMI activation, which in turn causes necrotic lesions and inflammation in the lungs causing permanent damage
28
What is a "disseminated infection" of TB?
When the TB spreads outside of the lung tissue - Technically granuloma formation can occur at any site in the body, such as the spleen
AKA military TB or extrapulmonary TB
29
What are the symptoms of active TB?
- Gradual onset, variable manifestations...
* ** Weight loss
* ** Night sweats
* ** Cough (possibly)
Other symptoms could include:
- Fatigue, weakness
- Fever
- Chest pain, SOB
30
What type of couch do you see in active TB?
Cough could be absent or mild with scant sputum
Severe productive cough with yellow/yellow-green/blood-streaked sputum (hemoptysis)
31
Why would this type of a cough occur?
Cell-mediated immunity is damaging your lungs and sores are forming
32
What are the symptoms of reactivation TB?
*****
Patients can often be asymptomatic for 2-3 years and be infectious ***
33
What occurs in reactivation?
Granulomas fall apart, Mtb can move to other parts of the lung, can be expectorate or aerosolized and transmitted to other individuals
Can spread systemically
34
What are the symptoms of reactivation TB once they eventually occur?
Symptoms similar to or the same as active TB
35
How do you diagnose latent TB?
- Rapid lab tests
| - Chest x-ray
36
What would you see in a chest x-ray of a patient with latent TB?
- Ghon focus
| - Ghon complex
37
What is a Ghon focus?
A lung lesion - the granuloma is seen on the chest x-ray because it has calcified and contains LIVE Mtb
38
What is a Ghon complex?
When you have BOTH a calcified granuloma AND an affected lymph node seen on the chest x-ray
39
How do you test a patient for active or reactivated TB?
- Symptoms
- Rapid lab test
- Chest x-ray
40
What will a chest x-ray of a patient with active or reactivated TB look like?
- Focal infiltration with cavitation
| - Often in the apical posterior segment of the upper lobes of both lungs
41
When should you consider TB?
In immunosuppressed patients with other diagnoses
42
What should you do when you suspect or confirm TB?
Report known or suspected cases of TB to the health department immediately
***
43
What is the laboratory diagnosis test for TB (immuno-diagnosis)?
- TB skin test
- IFN-gamma release assay
- Microscopy
44
What is the TB skin test?
- An intradermal injection of PPDs *** (puified protein derivatives), which are proteins derived from the Mtb cell envelope
45
What is a implication in the TB skin test?
BCG-vaccinated people will test positive
Which is why the US does not use this vaccine
46
What is the IFN-gamma release assay?
- Measures the IFN-gamma release by T-cells in whole blood stimulated with Mtb antigen (previously sensitized T cells)
47
Is this test okay to use with BCG-vaccinated patients?
Yes
48
What three things can you do with microscopy to diagnose TB?
- Ziehl-Neelsen or Kinyoun stains
- Nucleic Acid Amplification tests
- Culture
49
How will Mtb stain with Ziehl-Neelsen or Kinyoun stains?
***
Acid-fast staining because of lipid rich cell wall
Confirms mycobacterial disease but NOT specific to Mtb***
50
What nucleic acid amp tests can you do?
Commercial 1 hour test or PCR, which is expensive, but quick
51
What are the implications of an Mtb culture?
- Mtb slow growing
- Contamination issues = KOH or NaOH treatment of samples prior to culture
- Rapid culturing now 10-21 days down from 4-8 weeks
- Hard to keep it that sterile for that long
52
How do you treat TB?
4 drugs for 2 months...
- Isoniazid (INH)
- ethambutol
- pyrazinamide
- rifampin
Followed by 26 months of...
- INH
- rifampin
- Or an alternative drug combination
53
How effective is the TB treatment?
Risk of reactivation reduced 90% in patients with latent TB
54
Does it make sense to take these drugs then?
Yes - This makes sense to take the drugs – drastic reduction
55
What is important to know about Isonaizid?
****
- A prodrug
- Inhibits mycolic acid synthesis
- HEPATOTOXICITY and multiple adverse reactions
- Makes patient VERY sick and causes liver damage
*******
56
What issues do we commonly face in patients being treated for TB?
Compliance issues- side effects of isoniazid
57
What is the vaccine for TB?
BCG-vaccine
58
Which countries use this vaccine?
Not US
Used in endemic countries (most of Europe, Asia, Africa, South and Central America)
59
Is the BCG vaccine completely protective?
No, that's why we don't use it
60
Why else doesn't the US use it?
Can't use the cheap TB skin test
61
What is the relationship between TB and AIDS?
- Primary TB infection risk much greater in HIV infected individuals
- Progression to active TB much more likely in HIV infected individuals
- 200-300 times more likely to undergo reactivation
- More likely to have disseminated TB (like to spleen)
62
What is the leading cause of PREMATURE death in the world?
Tuberculosis and AIDS are the leading causes of premature death in the world ***
63
What is problematic about the strains of TB in Africa?
Multi- and extended-drug resistant strains are prevalent in populations with a high incidence of HIV infection
64
What is Mycobacterium avium-intracellulare?
A type of atypical, non-tuberculosis mycobacteria
- a complex of several mycobacteria
- leads to a pulmonary infection resembling TB in immunocompromised patients or with lung disease
65
What is mycobacterium kansasii?
A type of atypical, non-tuberculosis mycobacteria
- More common in the elderly
- Chronic gradulomatous pulmonary disease
- Seen in COPD patients
66
How do you diagnose and treat atypical, non-TB mycobacteria?
Similar to TB
67
What is different about TB and non-TB mycobacteria
Non-TB is...
- Less severe
- Not as fatal
68
What is the next section we are moving on to?
Laryngitis, Tracheitis & Epiglotitis
69
What are the symptoms of Laryngitis, Tracheitis & Epiglotitis?
Hoarseness and burning retrosternal pain
70
What is causing the symptoms?
Larynx and trachea have non-expandable cartilage rings in the wall
Inflammation and swelling of mucous membranes can lead to obstruction (especially in children)
71
What is the cause of Laryngitis, Tracheitis & Epiglotitis?
Most likely viral
72
What are some less common bacterial causes of Laryngitis, Tracheitis & Epiglotitis?
- GAS
- Haemophilus influenzae
- Staphylococcus aureus
73
What is Haemophilus influenzae serotype B
AKA HiB
| - a gram negative coccobacilli
74
What does fastidious mean?
Wikipedia
A fastidious organism is any organism that has a complex nutritional requirement. In other words, a fastidious organism will only grow when specific nutrients
75
What are the fastidious requirements of Haemophilus influenzae serotype B (HiB)?
Requires NAD and hemin for growth (chocolate agar
76
What does a "typed strain" of Haemophilus influenzae serotype B (HiB) mean?
***
It has a polysaccharide capsule of polyribosylribitol phosphate (PRP)
******
77
What does a non-typable strain?
No capsule
78
Which patient population does HiB mostly affect?
Pediatric patients
79
How do you transmit HiB?
Transmission via respiratory droplets or direct contact with respiratory secretions
80
What are the virulence factors of HiB?
***
- LPS exotoxin
- IgA protease
*** Typed strains have a polysaccharide capsule of polyribosylribitol phosphate (PRP) and are ANTIPHAGOCYTIC ***
81
How do you diagnose HiB?
Gram staining of a culture of blood, nasopharyngeal swab, sputum or spinal fluid
82
What happens in HiB gets to the brain?
Meningitis
83
What is the treatmetn for HiB?
- Severe cases – broad-spectrum cephalosporin
| - Less severe cases – amoxicillin (if sensitive)
84
What is the mortality rate of untreated HiB?
More than 90%
85
How do you prevent HiB?
Vaccination to combat H. influenzae type B
| ***
86
What type of vaccination is this?
Conjugate vaccine - PRP capsule liked to a protein carrier
87
What is bacterial acute bronchitis?
Inflammation of the tracheobronchial tree
88
What is the common bacterial agent in bronchitis?
Mycoplasma pneumoniae
89
Why does the Mycoplasma pneumoniae cause bronchitis?
***
The Adhesin/receptor combination has a strong affinity for the bronchial mucosal epithelium
***
90
What specifically does the mycoplasma pneumonia bind to?
Specifically the ciliated epithelium cells
91
What are the symptoms of bronchitis?
Dry cough
92
How do you treat bronchitis?
Just treat the symtpoms
93
What is the bacteria that causes the specific type of bronchitis called pertussis?
Bordetella pertussis
94
What is pertussis commonly called?
Whooping cough
95
What is the signature feature in whooping cough?
The paroxysmal cough ***
96
What causes this cough?
- High respiratory secretions
| - Low mucociliary clearance
97
What type of bacteria is bordetella pertussis?
Gram-negative coccobacilli
98
Is bordetella a fastidous bacteria?
Yes - it is highly susceptable to toxic metabolites
99
What is the disease mechanism of bordetella pertussis?
- Adhere to ciliated respiratory mucosa
| - Multiply, produce toxic factors (uses them to make the resp. epithelium secrete fluid)
100
What species do we see pertussis in?
Humans ONLY
101
What is a high risk population for pertussis?
Infection risk high for >1 yr old or unvaccinated
102
How do we spread pertussis?
Person to person and by aerosols
103
How long is the incubation period for pertussis?
7-10 days
104
When will symptoms peak?
1-2 weeks
105
How long will the infection last?
3-4 weeks
106
When will a bacterial culture be most positive?
1-2 weeks
107
When are you most likely to spread pertussis?
1-2 weeks
108
What are the two MAJOR adhesins in pertussis that act as virulence factors?
*******
Filamentous and Hemagglutinin
********
109
What do these adhesins mainly bind to?
Ciliated epithelial cells
110
What is the MAJOR toxin in pertussis that acts as a virulence factor?
Pertussis toxin (an AB toxin)
111
What is the function of this toxin?
****
Increases respiratory secretions *****
And leads to the paroxysmal cough *****
112
How do you diagnose pertussis?
- Pertussis is a clinical diagnosis
| - Laboratory tests to confirm
113
What laboratory tests can you do?
- Culture (Bordet-Gengou agar, 3-7 days growth (not routine))
- Nucleic acid amplification test (specific/sensitive – from throat swab/nasal swab or sputum)
- Microscopy (non-specific/insensitive)
- Serology can be confirmative
114
How do you treat pertussis?
1 - Supportive therapy (Oxygenated, eating, management)
2 - Macrolides (azithromycin, clarithromycin) to treat infection
115
How can you prevent pertussis?
******
Vaccination with DTaP (aP = acellular Pertussis)
116
What type of vaccine is DTaP?
Vaccine contains a detoxified pertussis toxin, peractin, filamentous hemagglutinin
117
How frequently do pertussis epidemics tend to occur?
Every 3-4 years
118
When was the last epidemic of pertussis?
2010
119
Do you need to know what type of sputum appearance is most indicative of the type of pneumonia or cause of pneumonia?
YESSSSSS
120
What is the most likely cause of a pneumonia that presents with sputum appearing purulent?
Typical pneumonia
121
What is the most likely cause of a pneumonia that presents with sputum appearing scant, watery and mucoid?
Interstitial pneumonia
122
What is the most likely cause of a pneumonia that presents with sputum appearing rust-colored?
Streptococcus pneumoniae
123
What is the most likely cause of a pneumonia that presents with sputum appearing thick, like currant jelly?
Klebsiella pneumonia
124
What is the most likely cause of a pneumonia that presents with sputum appearing with a large amount of blood?
Cavitary tuberculosis or lung abscess
125
What is the most likely cause of a pneumonia that presents with sputum that is foul smelling?
Anaerobic bacterial pneumonia
126
Case study:
A 8-year-old man is involved in an accident at home while playing in the basement near a natural gas furnace and incurs partial thickness burns to 20% of his body. In the hospital, he requires intubation and mechanical ventilation because of an inhalation injury. The patients develops systems consistent with typical pneumonia. A chest x-ray is taken (shown below). A sputum culture is taken and reveals the infection is caused by a gram-negative rod that is oxidase-positive and negative for lactose fermentation. Which one of the following options would be the best choice for treatment in this case?
Ticarcillin and an aminoglycoside
127
Case study:
A 46-yo man was admitted to the hospital with cough productive of purulent sputum, pleuritic chest pain, fever, & chills. His medical history included only hypertension & smoking. The patient’s temperature was 40°C; breath sounds were diminished at the right lung base, but there were bronchial breath sounds and rales just above that area. WBC count was elevated. A chest X-ray showed right lower lobe consolidation with right pleural effusion. A gram stain of a sputum sample shows a gram-positive cocci. Which one of the following is a component of a vaccine that is commonly administered to prevent infection by the most likely causative agent?
Capsular polysaccharide
128
Case study:
A 77-year-old female patient recently underwent knee replacement surgery. A surgical complication has required the patient to be on mechanical ventilation to assist with breathing for that last two months. The patient has spiked an abrupt fever of 41˚C, is now coughing up foul smelling sputum and complains that it is painful to breathe. A lung aspirate culture reveals a gram-negative rod, that is oxidase negative, grows anaerobically, and forms large mucoid colonies. Which of the following is a virulence factor produced by the pathogen that is causing the described infection?
Capsule
