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Flashcards in Mycobacterial Infections Deck (79):
1

Acute cough exists for less than?

Whats it most commonly due to?

Subacute cough is how long?
Chronic cough is longer than what?

Three weeks

most commonly due to an acute respiratory tract infection, PE, pneumonia

3-8 weeks
8 weeks

2

HOw is TB charcterized pathologically?
6

1. by inflammatory infiltrations,
2. formation of tubercles, caseation,
3. necrosis,
4. abscesses,
5. fibrosis, and
6. calcification

3

What kind of pts account for 30-50% of the increase in TB?

HIV infected pts

4

Why do we do an acid fast stain?

Contains mycotic acid and needs the acid fast

5

Inhalation and deposition in the lungs leads to one of four possible outcomes. What are they?
4

1. Immediate clearance of the organism
2. Chronic or latent infection
3. Rapidly progressive disease (or primary disease)
4. Active disease many years after the infection (reactivation disease)

6

People with untreated active TB will die within how many years?

50% die 2 years

7

Chronic or Latent Infection
of TB is what?
3

This is the person that comes in with a positive PPD but who is asymptomatic, with a clear CXR.

8

Pathogenesis of TB?
3

1. Small bacilli carried in droplets small enough (5 to 10 µm) to reach the alveolar space
2. Bacilli proliferate inside alveolar macrophages and kill the cells
3. Infected macrophages produce cytokines and chemokines that attract other phagocytic cells, which eventually form a nodular granulomatous structure called the tubercle or
Gohn Focus

9

What phagocytic cells do the TB infected macrophages attract with cytokines and chemockines?
3

1. monocytes,
2. other alveolar macrophages, and
3. neutrophils

10

IF the bacterial replication is not controlled what happens?


What does this lead to?
2

tubercle enlarges and the bacilli enter the local draining lymph nodes

lymphadenopathy, a characteristic manifestation of primary TB

Caseation(cell necrosis-looks like cheese)/fibrosis/calcification
Ghon complex

11

What stage determines if the pt will have primary disease or chronic or latent TB?

Initial inflammatory granulomatous tubercle formation
--If bacterial replication is controlled here, patient will NOT develop primary disease and is said to have chronic or latent infection

12

What is the Ghon complex?

eponym which describes an inflammatory nodule in the pulmonary parenchyma (Gohn focus) with an accompanying hilar adenopathy, in line with lymphatic drainage from that pulmonary segment

Enlargemnt of tubercle and infiltration of lymph system!!

13

Frontal chest radiograph shows a calcified right lung nodule with associated calcified hilar lymph nodes.
What is this describing?

Ghon complex
(end is that the complex becomes calcified)

14

In those who develop active disease within the first two to three years after infection, it will cause severe illness. Including?
2

Lung necrosis
Extrapulmonary

15

Main symtpoms of pulmonary TB:
CNS?2
Lungs?3
Skin?2

1. appetite loss and fatigue
2. CHest pain, coughing up blood, productive prolonged cough
3. night sweats, pallor

16

Where does the infection proliferate?

inside the alveolar macrophages

17

Whats the distinct lymphadenopathy you would identify in TB?

Hilar lymphadenopathy
(need to look for this on an XRAY)

Can be calcified noduels in the lung/apex and in the hilar region

18

HOw does Secondary infection/Reactivation occur?
4
(what is important to note here?)

What is the bacteria doing in a reactivation infection?

1. Asymptomatic primary infection occurs!!!!
2. Cell-mediated immunity
3. Dormancy
4. Then, recurrance may occur

Results when the persistent bacteria in a host suddenly proliferate
(immunocomprimised)

19

Secondary/Reactivation is Clearly associated with immunosuppression and can be seen in the following circumstances?
5

1. HIV infection and AIDS
2. End-stage renal disease
3. Diabetes mellitus
4. Malignant lymphoma
5. Corticosteroid use

20

In contrast to primary disease, the disease process in reactivation TB tends to be what?

What is there little of compared to a primary infection?

Where do the lesions in secondary infections usually occur?

Localized (ghon region is reactivated)


there is little regional lymph node involvement and


the lesion typically occurs at the lung apices

21

Symptoms of Secondary/Reactivation infection?
6

1. Cough, hemoptysis
2. Persistent fever/night sweats
3. Weight loss
4. Malaise
5. Adenopathy
6. Pleuritic chest pain

22

What is Miliary Tuberculosis?

If the bacterial growth continues to remain unchecked, the bacilli may spread hematogenously to produce disseminated TB

miliary TB is now used to denote ALL forms of progressive, widely disseminated hematogenous tuberculosis, even if the classical pathologic or radiologic findings are absent.

23

Acute miliary TB presents how?
2 early
3 late

Who does it tend to infect?

1. High fevers
2. Night sweats

1. Occ. Resp distress
2. septic shock,
3. multiorgan failure

young pts

24

Chronic miliary TB presents how?
3

Who does it tend to infect?

1. Fever
2. Anorexia
3. Weight loss

Particularly in the elderly (FTT)

25

Extrapulmonary Manifestations of TB?
6

Frequency?
History?
Imagining?
Most commonly infection type?
Treatment?

1. Frequency is increasing
2. Past history is unreliable
3. 50% have normal chest radiographic findings
4. Clinical features vary widely
5. Most common type is infection of an individual organ system
6. In most cases, same regimens used for pulmonary TB are used

26

Extrapulmonary Manifestations:
PLaces where it can move to and affect?
7

1. Pleural/Pericardial effusions
2. Lymph node infection! (Scrofula)
3. Kidney
4. Skeletal (potts- in the spine)
5. Joints
6. CNS
7. Intraabdominal/GI

27

What kind of infections would be caused by CNS tuberculosis?
3

1. Meningitis;
2. Intracranial tuberculoma; 3. spinal tuberclous arachnoiditis

28

What kinds of Intraabdominal infections can be caused by TB?
4

1. GI tract;
2. peritoneum;
3. renal tuberculosis;
4. testicular granuloma

29

Most common cause of pericardial constriction in other countries?

TB

30

Most persons diagnosed with TB are begun on specific treatment before the diagnosis is confirmed by the laboratory (why do you think this is true?)

It can take months to grow the organims in the agar so you start it early

31

What constitutes a positive PPD?

10mm induration

32

What kind of technique will be used to examine Sung’s sputum?

Acid fast stain

33

What is the most important thing to understand about culturing for Mycobacterium?

Its going to take a long time to grow it so you should start treatment before

34

Whats the most sensitive test for the diagnoses of infection with a mycobacterium tb?

Far more sensitive than what?

Positive tuberculin skin test does NOT by itself prove the presence of active disease but DOES indicate that what has occured?

Tuberculin Skin Testing

chest radiography



Infection

35

What is the primary use of skin testing?

Primary use is in detection of Latent TB Infection (LTBI)

36

Testing is targeted in persons at high risk for what?
2

1. developing symptomatic TB who would benefit by treatment of LTBI or

2. those patients at increased risk for primary TB should they acquire infection.

37

What exactly is used with the Tuberculin Skin Test?

Purified Protein derivative

38

Importance of Technique with Tuberculin Skin Testing
2 things

What will subcutaneous administration result in?

1. MUST be done intradermally
2. MUST form a visible wheal with injection

(subcutaneous administration will result in a false-negative test if the patient indeed has been infected by TB!)

39

Importance of Reading Test Appropriately 3


1. MUST be read at 48-72 hours
2. Test is read by the diameter of the induration, NOT the diameter of erythema!
3. Finger versus Ballpoint pen method

40

Why is a TB skin test read late/describe the reaction?

(reaction is from delayed type hypersensitivity response mediated by T lymphocytes)

41

Indications for TB skin test screening?
8

1. HIV infection
2. Ongoing close contact with cases of active TB
3. Presence of medical condition that increases the risk of active TB
4. Medically underserved, low-income population
5. Residence in long-term care facility
6. Single potential exposure to TB (e.g. diagnosis of TB in a family member)
7. Presence of incidentally discovered fibrotic lung lesion
8. Immigrants and refugees from countries with a high prevalence of TB

42

What are examples of close contact with cases of TB on an ongoing basis?
3

Health care workers
Prison guards
Mycobacterial lab personnel

43

Presence of medical condition that increases the risk of active TB
Examples?
5

Examples include:
1. diabetes mellitus,
2. steroid therapy or other immunosuppressive agents
3. certain types of malignancies,
4. end-stage renal disease,
5. alcoholism

44

The interval from primary infection to tuberculin skin test conversion?

mean of about 6 weeks but could be up to 8 weeks.

exposure

45

Sources of false-negative tests?
7

1. Inadequate nutrition
2. Anergy
3. Nontubercular mycobacterium
4. Simultaneous presence of immunosuppressive disorder
5. Concurrent viral infection
6. Corticosteroid therapy
7. Bad skin testing technique

46

Guidelines for Determining Positive Tuberculin Skin Test:

Who is positive with a >5mm in induration?
4

1. HIV positive persons
2. Recent contacts of TB case
3. Fibrotic changes on chest radiograph consistent with old TB
4. Patients with organ transplants and other immunosuppressed patients (receiving the equivalent of >15 mg/d Prednisone for >1 mo)

47

Guidelines for Determining Positive Tuberculin Skin Test:

Who is positive with a
Induration >10 mm?
6

1. Recent arrivals (10 percent of ideal body weight, gastrectomy, jejunoileal bypass
6. Children

48

Guidelines for Determining Positive Tuberculin Skin Test:

Who is positive with a
Induration of 15mm?

Persons with no risk factors for TB

49

How about persons who have received BCG (Bacille Calmette-Guerin) vaccine (when should testing be done?)2

How will children react if they got the vaccine?




TB skin test responses indicative of new TB infection include:
Measurements under35?
Measurements over 35?

1. Baseline testing should be done several months following vaccination
2. Subsequent tests can be compared to baseline tests to evaluate the likelihood of true TB infection



Children who have received this vaccine generally demonstrate PPD reactions of 3 to 19mm several months after vaccination

1. Increase in skin test reactivity of > 10mm induration in persons less than 35yo
2. Increases in reactivity of > 15mm induration in persons greater than 35yo

50

If baseline values for PPD are unavailable, reactivity should be interpreted and treated as what?

unvaccinated persons

51

When active disease is suspected, there should be examination of sputum for what?2

If patient unable to produce sputum spontaneously, attempts should be made to induce sputum
4

Acid Fast Bacilli Staining and
Mycobacterium culturing


1. Hydration
2. Pulmonary physiotherapy
3. Mucolytic agents
4. Bronchoscopy or bronchoalveolar lavage may be necessary

52

One distinguishing feature of the organisms belonging to the genus Mycobacterium is their?

Unlike gram-negative bacteria, there is no?

The envelope is composed of a number of different macromolecules including what?

cell envelope


true outer membrane in Mycobacterium.



Mycolic acid

53

Is the AFB smear only specific for TB?

No
other acid-fast organisms will be positive such as Mycobacterium avium)

54

What are the two versions of AFB smear?


Which one is more sensitive and why?

1. Fluorochrome staining (Increases sensitivity, decreases examination time versus Ziehl-Neelsen method)
2. Ziehl-Neelsen method (the older method)

55

What is the gold standard for mycobacterium staining?

mycobacterium culturing

56

Although M. tuberculosis can grow on simple carbon and inorganic nitrogen sources, one distinguishing feature of this organism is its?

Slow growth rate

57

What are the two types of media for mycobacterium culturing?

What are the mediums called and how long does each take to grow?

1. Solid media

Lowenstein-Jensen or Middlebrook

Takes up to eight weeks or longer to detect growth

2. Liquid media

Broth formulations include BACTEC 460, ESP, MGIT

More rapid and can detect growth of mycobacteria in clinical samples in as few as seven days

58

Whole-blood interferon-gamma assay (e.g. QuantiFERON-TB Gold test)
is a screening for what?

Describe why it identifies the infection even in asymtomaic pts?

asymptomatic disease


T cells of individuals previously sensitized with tuberculous antigens will produce interferon-gamma when they reencounter mycobacterial antigens
(antibodies are present)

Can be used in all circumstances in which PPD is used

59

What might be some of the advantages of this test over the traditional TST with PPD?
5

1. Subject to less testing error
2. Subject to less reader bias and error
3. Can be accomplished after a single patient visit
4. May not be as likely to be positive following BCG vaccination
5. The RD1 antigens used in this testing are not shared with most nontuberculous mycobacteria.

60

Rapid Nucleic Acid Assays can produce results how quickly?

Why is it not done as often?


Who is it reccommended for and why?

Can produce results within two to seven hours after sputum processing

Requires higher level laboratories (technical expertise and skill are necessary for reliable results)

Highly specific for Mycobacterium Tuberculosis and is generally recommended on all AFB smear-positive respiratory specimens

61

Describe the shape of mycobacterium and describe their cell walls?

How do they react to anitbacterials?

Mycobacterium are rod-shaped bacteria with lipid-rich cell walls

They grow very slowly and take a long time to eradicate with antibacterials

62

What is the most important thing to educate our TB pts about treatment?
3

1. Drugs MUST be taken in appropriate doses
2. Drugs MUST be taken regularly
3. Therapy MUST continue for a sufficient period of time

63

Tb treament for a latent infection?

Alternative?

Generally the recommendation is nine months of Isoniazid (INH) monotherapy

Rifampin PO daily x 4 months

64

Active TB Disease
treatment?
4



Preferred initial therapy includes:
Isoniazid (INH)
Rifampin (RIF)
Pyrazinamide (PZA)
and Ethambutol (EMB)

65

MOA for Isomiazid?

Covalently binds to and inhibits enzymes essential for the synthesis of mycolic acid (key component of the cell wall)

66

Why INH never used alone?

as resistant organisms will rapidly emerge

67

What do we need to monitor with pts on INH?
2

Whats the most common?

Whats it associated with?

1. Hepatotoxicity, must monitor liver enzymes
2. Most common side effect is peripheral neuritis which manifests as paresthesias and is

associated with pyridoxine (vitamin B6) deficiency

68

Treatment for reactivation TB?

Requires at least 2 effective drugs because of the increased incidence of drug resistance

69

What is different about Rifampin (RIF) than INH?

MOA?

Broader antimicrobial activity than isoniazid

Blocks transcription by interfering with the beta subunit of bacterial RNA polymerase (doesn’t mess with human enzymes however ☺)

70

Who else is Rifampin effective against? 2


What infections is it used to treat prophylactically?
1 disease
2 infections

In addition to mycobacteria, is effective against many gram-positive and gram-negative organisms

Frequently used prophylactically for individuals exposed to

meningitis caused by

1. meningococci or
2. haemophilus influenzae

71

What to watch for in rifampin pts? 2


How would this affect other treatments?

1. Hepatotoxicity, liver enzymes
2. Inducer of cytochrome P450 enzymes and

therefore the patient may need higher dosage requirements for other drugs metabolized by this system

72

Pyrazinamide (PZA)
is only seen where?

What to watch for with these pts?
2

Only seen in antitubercular combo packages

What to watch for:
1. Extensively metabolized by the liver, must watch for hepatotoxicity!
2. Gout

73

Ethambutol (EMB)
MOA?

What to watch for?
Key to monitoring this?

inhibits an enzyme important for the synthesis of the mycobacterial arabinogalactan cell wall

Optic neuritis which results in diminished visual acuity and loss of ability to discriminate between red and green

Key here? Visual acuity should be periodically examined and drug should be removed if symptoms develop

74

Alternate second-line drugs
for TB management?
6

ASAs
Capreomycin
Cycloserine
Ethionamide
Fluoroquinolones
Macrolides

75

If the TB is mildly drug resistance what is our treatment plan? 2

Extremely drug resistant what is our treatment plan? 4
-how long is tretment?
-What is often required?

1. Multi-drug resistance
Isoniazid & Rifampin

2. Extremely drug resistant
Isoniazid, Rifampin, a fluoroquinolone, and an injectable (aminoglycoside)

18-24 months tx
Surgery often required

76

What is a big problem with pt education in TB?

Complicance is bad. And if they are taking it enough it wont work.

DOT therapy.
directly observed therapy (“DOT”)

77

It is important to know in what populations TB prevalence is highest including?
4

1. foreign born immigrants,
2. low socioeconomic groups,
3. HIV patients, and
4. drug users

78

The great majority of individuals infected with TB have what form?

latent disease (which is why screening is so important)

79

Classic chest xray of a patient with reactivation disease includes?

upper lobe apical infiltration with cavitation

(remember, reactivation disease tends to be local)