Mycobacteria Flashcards

(51 cards)

1
Q

What is the difference between a TB infection and TB disease?

A

TB Infection - Positive skin test
Normal immune function means that only 7-10% of people with TB infection will progress to develop TB Disease

TB Disease is active disease, commonly with upper lung infiltrate or cavitation

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2
Q

Which people are most likely to be infected with TB?

A

Close contacts of an active case

Foreign-born people

Medically underserved, low income

Homeless; Migrant farm workers

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3
Q

Who is more likely to progress from a TB infection to disease?

A

HIV infection (immunocompromised)

Recently infected with TB

Silicosis predisposes to TB

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4
Q

How is TB transmitted?

A

Airborne, so close contacts at high risk

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5
Q

Describe the basic pathogenesis of TB

A

TB gets inhaled and gains access to alveolar macrophages. May spread to regional lymph nodes and has a bloodborne spread.

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6
Q

Describe the basic immune response to TB infection

A

TB antigens swallowed and presented macrophages to CD4 T cells, which release cytokines to activate macrophages. See caseous necrosis with granulomas

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7
Q

What are the two potential outcomes of a Primary TB infection?

A

Latent TB infection (over 90%)

Progression to active TB disease (less than 10%)

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8
Q

What are the potential manifestations of TB Disease?

A

80-90% get an upper lung infiltrate with cavitation

10-15% get extrapulmonary manifestations from initial bloodborne spread (meninges, heart, bone, GU)

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9
Q

What is the Ghon focus?

A

The primary local area of infection, seen on CXR

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10
Q

What si the Ranke Complex?

A

When a Ghon focus becomes calcified, it becomes known as a Ranke Complex

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11
Q

What are common sites for Extrapulmonary TB?

A
Brain
Epiphyses of long bones
Kidneys
Vertebral bodies
Lymph nodes
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12
Q

Describe the PPD Skin Test

A

Intradermal inoculation of TB antigen. If there was a TB infection, you would see a lump of CD4 lymphocytes having a response a few days later

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13
Q

Describe the Quantiferon Gold Test

A

In vitro blood test that senses how much IFN-y is released when exposed to TB antigen

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14
Q

Describe the NAAT

A

NAAT= Nucleic Acid Amplification Test

Take a sputum sample, submit to lab, they do a PCR-like assay to assess for evidence of TB-like antigen

Rapid diagnosis!

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15
Q

Describe the use of Acid-Fast staining for TB detection

A

This stains the organisms red with blue background staining

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16
Q

Describe the use of bacterial culture in TB diagnosis

A

Liquid media can be more rapid, but in general, culture media can take many weeks to grow.

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17
Q

Where are nontuberculous mycobacteria most commonly acquired?

A

Bioaerosols
Water
Soil
Nosocomial

NOT human-to-human transmission

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18
Q

What are predisposing conditions for a Nontuberculous Mycobacteria infection?

A

Preexisting underlying lung abnormality (COPD, bronchiectasis, IPF, congenital abnormalities)

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19
Q

Where are infections with Nontuberculous Mycobacteria usually contained?

A

They are usually contained in the lung, but they may spread in AIDS patients

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20
Q

You suspect that a patient has TB. Is it more likely that they have TB or an NTM disease?

A

NTM disease

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21
Q

List some basic principles of TB treatment.

A

Multi-Drug Therapy (reducing emergence and enhancing response rates/cures)

Increase adherence

Long duration therapy (at least 6 months)

22
Q
Isoniazid HCl (INH)
Clinical Use
A

May be used as monotherapy in LATENT TB infection

First line drug for active pulmonary TB, used in combo with at least 2 others

23
Q
Isoniazid HCl (INH)
MOA
A

Prodrug, activated by catalase peroxidase (TB katG gene)

Targets inhA gene product, inhibiting TB cell wall synthesis (mycolic acid)

24
Q
Isoniazid HCl (INH)
Resistance Mechanisms
A
Mutations in either...
katG gene (prevents activation of prodrug to active form)

inhA gene (cell wall/mycolic acid synthesis)

25
``` Isoniazid HCl (INH) Toxicity ```
Hepatotoxicity (monitor baseline liver enzymes and their changes over time) Neurotoxicity Hypersensitivity rxns
26
Rifampin | Clinical Use
First line drug for TB, always used in combo Could also be used in combo for S. aureus, N. meningitidis (meninigitis prophylaxis)
27
Why can't Rifampin be used alone as an antibacterial agent?
Rapid development of resistance
28
Rifampin | MOA
Inhibits DNA-dependent RNA polymerase encoded by rpoB gene
29
Rifampin | Resistance Mechanisms
rpoB mutations
30
Rifampin | Toxicity
Hepatotoxicity (increased with INH) Red discoloration of urine and tears Influenza syndrome - more common in intermittent dosing Thrombocytopenia
31
Rifampin | Drug Interactions
Interacts with over 100 drugs Accelerates clearance and reduces effective serum concentrations of.... Warfarin, Estrogen, Anticonvulsants, Antiretroviral drugs
32
Ethambutol | Clinical Use
"Helper" drug that inhibits resistance to other drugs
33
Ethambutol | MOA
Inhibits TB arabinosyl transferase encoded by embB gene
34
Ethambutol | Toxicity
``` Optic neuritis (blurred vision, could cause blindness) Periphral neuropathy ```
35
Pyrazinamide (PZA) | Clinical Use
First line TB drug for the 1st two months of therapy | Good penetration into CSF in tuberculous meningitis
36
Pyrazinamide (PZA) | MOA
Prodrug activated y TB pyrazinamidase, encoded by pncA gene
37
Pyrazinamide (PZA) | Toxicity
Hepatitis
38
Streptomycin | Clincial Use in TB infection
Second line TB drug
39
Streptomycin | MOA
Inhibits protein synthesis by binding ribosome
40
Streptomycin | Toxicity
Ototoxicity | Nephrotoxicity
41
What is the difference between primary and secondary resistance with TB?
Primary- infection of a TB disease that is ALREADY drug resistant Secondary- an initially susceptuble TB population was selected for resistance
42
What are some factors that can select for drug resistance?
Too few drugs | Suboptimal drug dosing or absorption
43
How do you calculate the risk of multi-drug resistance developing?
Risk of evolution of resistance to two drugs is the PRODUCT of the risk of the development of resistance to each drug
44
Define Multi-Drug Resistant TB
Resistance to both INH and rifampin
45
When you discover that the TB disease is resistant to rifampin, how does that change your therapy?
Rifampin resistance eliminates short course (6 mo) TB therapy Now, the pt will need 18-24 months of therapy
46
What is the typical multi-drug therapy for TB?
``` 4 drug regimen = RIPE in initial phase Rifampin INH PZA Ethambutol ``` Continuation phase- only INH and rifampin
47
Describe the use of intermittent therapy for TB
2-3x weekly dosing Only done with Directly Observed Therapy A nurse visits the patient's house multiple times weekly to dose them
48
What are the three methods used to treat a LATENT TB infection?
INH monotherapy for 9 months Rifampin monotherapy for 9 months, daily INH + Rifapentene (once weekly, DOT regimen)
49
Which drugs are used to treat both TB and NTM infections?
Rifampin Ethambutol Fluoroquinolones Aminoglycosides
50
Which drugs are used to treat exclusively Non-tuberculous mycobacterial infections?
Clarithromycin | Azithromycin
51
What combination of drugs is used to treat leprosy?
Rifampin and Dapsone for 12 months, daily