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Clinical 2 - Antibiotics > 10 - Tuberculosis > Flashcards

10 - Tuberculosis Flashcards

1
Q

What 2 types of populations have a higher incidence of Tb in Canada?

A
  • Canadian-born Aboriginal

- Foreign born

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2
Q

What province/territory has highest incidence of Tb ?

A

North (the territories)

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3
Q

What bug causes Tb?

A

Mycobacterium tuberculosis

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4
Q

Describe Mycobacterium tuberculosis

A
  • bacillus
  • aerobic and anaerobic, intracellular and extracellular
  • slow growing, latent, dormant states
  • multi-drug resistance

**using 1 drug to treat Tb is not effective

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5
Q

Describe the transmission of Tb

A
  • communicable disease, aerosolized droplets
  • enters bronchioles and alveoli, settles in lower lobes
  • first-line macrophage-mediated immunity
  • followed by T-cell immunity over 2-8 weeks
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6
Q

What are the risk factors for Tb?

A
  • close contacts especially laryngeal or pulmonary TB (positive smear/culture stages)
  • endemic areas (Northern Canada)
  • poor or crowded living conditions, homelessness, correctional facilities
  • healthcare workers
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7
Q

Of those who get the initial infection, how many develop the disease and how many have a latent Tb infection?

A

5% have primary disease

95% have latent TB infection

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8
Q

Of those who have the latent TB infection, how many will have a reactivation and how many will have no disease?

A

5% will have a reactivation of Tb

90% will have no disease

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9
Q

Describe a latent TB infection?

A
  • asymptomatic or mildly symptomatic, non-contagious
  • normal X-ray, negative sputum stain and culture results
  • lymphatic spread to regional nodes, lung apices .. less commonly bone marrow, liver, spleen, kidney, meninges
  • latent or dormant in seeded foci (Ghon nodes) for months to years
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10
Q

How do we diagnose a latent Tb infection?

A

1) TST (Tuberculin skin test)
- heat sterilized, purified protein derivative
- delayed T-cell hypersensitivity response, induration within 48-72 hours
- false negative results if cutaneous anergy (pre-conversion, neonate, elderly, HIV, lymphoma, chemotherapy, corticosteroids); use positive control mumps or Candida
- does not distinguish latent from active disease !!!!, other mycobacterial infection or prior BCG vaccine

2) IGRA - interferon gamma release assay
- blood test measures T-cell release of IFN-gamma
- does not distinguish latent from active disease; more specific than TST in patients vaccinated with BCG

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11
Q

What does a TST result > 10 mm mean?

A

TST conversion (within 2 years)

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12
Q

In people who have been exposed to Tb in the past 2 years, they are at a higher risk of it becoming active. If you give them prophylaxis, you can reduce activation by ____%.

A

90%

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13
Q

What is the treatment for latent TB infection?

A

INH daily x 9 months

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14
Q

What is an alternative treatment for latent TB infection?

A

RMP daily x 4 months

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15
Q

INH and RMP are both associated with ______

A

hepatotoxicity

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16
Q

Primary TB:

Early progression typically within ____ months of exposure

A

4-12

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17
Q

Primary TB:

Risk factors?

A
  • age

- immune function

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18
Q

Primary TB:

Most common in ?

A

lymph node or pleural disease

in lungs

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19
Q

Primary TB:

Disseminated including CNS more common in ?

A

infants, immunocompromised

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20
Q

Reactivation TB:

Late progression ____ months or longer after exposure

A

18-24

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21
Q

Reactivation TB:

Most common upper lobe pulmonary disease (_____)

A

pneumonia

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22
Q

Reactivation TB:

Extra-pulmonary more common in _______

A

immunocompromised

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23
Q

What are some high risk factors for active TB infection ?

A
  • AIDS/HIV
  • Transplant
  • Lung disease (silicosis)
  • Hemodialysis
  • Carcinoma in head and neck
  • Recent TB infection in the past 2 years
  • Abnormal chest x ray
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24
Q

Clinical signs and symptoms of active Tb ?

A
  • dry then productive cough > 2 weeks
  • hemoptysis (coughing up blood), chest pain
  • fever, night sweats
  • anorexia, weight loss (advanced disease)
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25
Q

What type of microbiological testing occurs for active Tb?

A
  • acid-fast bacilli (AFB) smear stain is rapid and inexpensive, positive results in over 50% of cases (modest sensitivity)
  • mycobacterial culture/susceptibility testing is gold standard (2-8 weeks for complete results)
  • molecular diagnostics (PCR) and susceptibility screening
26
Q

A radiograph is not ______

A

conclusive

27
Q

Treatment of active TB infection:

___% mortality without treatment

28
Q

Goals of treating an active TB infection ?

A
  • rapidly kill and eliminate MTB to cure clinical disease (without relapse), prevent complications and reduce mortality
  • prevent antimicrobial resistance
  • prevent transmission
29
Q

What are the principles of anti-TB drugs?

A
  • Combination therapy optimizes MTB killing & prevents resistance
  • Adherence optimizes efficacy and minimizes resistance
  • Drug dosing, PK-PD and role of TDM (therapeutic drug monitoring) not well understood
  • Follow-up sputum samples monthly until 2 consecutive negative culture results, predicts cure
  • Isolation to prevent transmission for initial 1-2 weeks and until 3 consecutive negative AFB smears
30
Q

What is Regimen 1 for treating Tb?

A

Initial phase (first 2 months):

  • INH - isoniazid
  • RMP - rifampin
  • PZA - pyrazinamide
  • EMB - ethambutol

daily or 5 days/week

Continuation phase:

  • INH for 4 months
  • RMP for 4 months

daily or 3 times/week

31
Q

What is Regimen 2 for treating Tb ?

A

Initial phase (first 2 months):

  • INH - isoniazid
  • RMP - rifampin
  • EMB - ethambutol

daily or 5 days/week

Continuation phase:
-INH for 7 months
RMP for 7 months

daily or 3 times/week

32
Q

What is the Regimen for the elderly?

A

Initial phase (first 2 months):

  • INH - isoniazid
  • RMP - rifampin
  • EMB - ethambutol

daily or 5 days/week

Continuation phase:
-INH for 7 months
RMP for 7 months

daily or 3 times/week

33
Q

What is the Regimen if you’re pregnant ?

A 
Initial phase (first 2 months):
-INH
-RMP
-EMB
\+/- PZA

daily or 5 days/week

Continuation phase:

  • INH
  • RMP
  • for 7 months if PZA not used
  • for 4 months if PZA used

daily or 3 times/week

34
Q

Why is EMB (ethambutol added) ?

A
  • incase there is restart bug to one or more of the first 3 meds
  • it is D/C at the time that you know it is sensitive to the other 3 meds
35
Q

Dose of Isoniazid?

A

300 mg daily

36
Q

Dose of Rifampin?

A

600 mg daily

37
Q

Dose of Pyrazinamide?

A

20-25 mg/kg daily

38
Q

Dose of Ethambutol?

A

15-20 mg/kg daily

39
Q

Which meds need dosage adjustment with renal failure?

A

Pyrazinamide

Ethambutol

40
Q

What dose of Pyrazinamide should be recommended for a CrCl < 30 or on hemodialysis ?

A

25-35 mg three times/week

*normal dose = 20-25 mg/kg DAILY

41
Q

What dose of Ethambutol should be recommended for a CrCl < 30 or on hemodialysis ?

A

15-25 mg three times/week

*normal dose = 15-20 mg/kg DAILY

42
Q

What are the 1st line agents?

A
  • Isoniazid
  • Rifampin
  • Pyrazinamide
  • Ethambutol
43
Q

Describe:

Isoniazid

A
  • extra-cellular (doesn’t go into cells)
  • bactericidal
  • inhibits protein, nucleic acid, lipid, mycelia synthesis in cell division
44
Q

Describe:

Rifampin

A
  • intra/extra-cellular
  • bactericidal
  • inhibits DNA-dependent RNA polymerase
45
Q

Describe:

Pryazinamide

A
  • intra-cellular
  • rapidly bactericidal
  • converted to pyrazinoic acid
  • toxicities of PZA limit it’s long term use
46
Q

Describe:

Ethambutol

A
  • intra-cellular
  • bacteriostatic
  • inhibits metabolite & RNA synthesis
47
Q

Why is EMB not the optimal anti-Tb drug?

A

bc it’s static, not cidal

-only added on in case of resistance to the other 3 bugs

48
Q

When are the 2nd line agents used?

A

if there is first-line drug resistance or intolerance

49
Q

What are the 2nd line agents used for Tb?

A
  • Fluoroquinolones (Levo/Moxi)

- Aminoglycosides (Amikacin/Streptomycin)

50
Q

% of adverse effects for INH + RMP + PZA

51
Q

% of adverse effects for INH + RMP

52
Q

% of adverse effects for INH

53
Q

Side effects of INH

A
  • Hepatotoxicity - LFTs, hepatitis, necrosis
  • Hypersensitivity
  • Peripheral neuropathy
  • Nausea, vomiting
54
Q

What does hepatotoxicity increase with?

A
  • increases with age, female, pre-existing liver disease, alcohol consumption, other hepatotoxins
  • Monitor baseline at 2 weeks and monthly
55
Q

INH is an inhibitor of CYP 2C9 and 3A4 which means it interacts with what drugs?

A
  • phenytoin
  • carbamazepine
  • warfarin
56
Q

______ reduce absorption of INH

57
Q

Side effects of Rifampin

A
  • hepatotoxicity
  • hypersensitivity
  • nausea, gastritis
  • orange-red discolouration of saliva, urine, tears
58
Q

What does Rifampin induce ?

A

CYP 2C9 and PgP

59
Q

Side effects of PZA ?

A
  • hepatotoxicity
  • hypersensitivity
  • hyperuricemia, arthralgias
  • nausea
60
Q

Side effects of EMB?

A
  • ocular neuritis (dose dependent)
  • hypersensitivity
  • CNS, peripheral neuritis

*eye exams are indicated for ppl on EMB

61
Q

How would you treat a drug-induced rash while on Tb meds?

A
  • D/C TB drugs and start FQ + other second line agent (like Amikacin)
  • Review history for other possible causes
  • When rash resolves, restart one TB drug (ex. INH)
  • After 3 days, restart second TB drug (ex. RMP)
  • After 3 days, restart EMB

*Once you know INH and RMP are fine, D/C FQ

  • After 3 days and if rash does not recur, assume PZA
  • If rash recurs with any of the above, discontinue agents dn start all remaining TB drugs
  • Adjust regimen based on agents discontinued
62
Q

How would you treat a drug-induced hepatitis while on Tb meds?

A
  • Discontinue TB drugs and start FQ + other second line drug
  • Review history for other possible causes, alcohol or other medications
  • Check viral hepatitis serologies
  • When transaminases return to normal, restart RMP
  • After 2 weeks, restart INH (unless initial severe toxicity ex. ALT > 1000)
  • After 2 weeks, if transaminases remain normal assume PZA
  • If hepatitis recurs with any of the above, D/C agent and start all remaining TB drugs
  • Adjust regimen based on agent’s discontinued

Clinical 2 - Antibiotics (14 decks)

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