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TB Flashcards

1
Q

Mycobacterium tuberculosis characteristics

A

Obligate aerobic bacteria
Slow growing
- Can take weeks-months to get culture results
Waxy cell membrane
- Does not allow Gram-stain to penetrate
Acid fast bacilli
- AFB smear positive

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2
Q

Types of TB

A

1) Active TB
- Symptomatic
- Actively replicating

2) Latent TB
- Asymptomatic, not infectious
- Not actively replicating
- May develop into active TB later on in life
• Cumulative lifetime risk i.e. children have higher risk VS elderly (longer life left)

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3
Q

Pathophysiology

A

Transmission: Airborne (98% of cases)

M. tuberculosis accesses lower airways:

1) Consumed by macrophages –> no infection OR
2) Bacteria replicates in lungs
- Due to inadequate immune response
- Latent TB –> cellular immune system is able to contain infection
- Active TB –> unable to contain infection

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4
Q

Epidemiology

A 
Worldwide:
2018
- ~10 million new cases
- ~1.5 million deaths 
Most affected regions: SE Asia, Africa, Western Pacific 
SG:
2018: 1565 new cases
- 50% in foreign born individuals
- 2/3 in > 50 years 
#5 cause of CAP  
- Anyone with unexplained cough ≥ 3 weeks should be evaluated for TB
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5
Q

Risk factors

A

Latent & active TB:

1) Living in urban areas
2) Living in prisons, nursing homes, homeless shelter
3) Close contact with pulmonary TB patients
4) Co-infection with HIV

Active TB

1) Children < 2 years
2) Elderly > 65 years
3) Immunosuppressed
4) Malnutrition
5) Co-infection with HIV

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6
Q

Site of infection

A

Most common: Pulmonary infection
Extra-pulmonary TB possible (e.g. bone & joints, CNS)
- Antibiotics used similar but may require longer duration / adjunctive treatment

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7
Q

Clinical presentation - Signs & symptoms

A

1) Weight loss
2) Fatigue
3) Productive cough
4) Fever
5) Night sweats
6) Hemoptysis

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8
Q

Clinical presentation - Differential diagnosis

A

Signs & symptoms generally similar to pneumonia
- Night sweats & hemoptysis more classical for TB

Differential diagnosis based on duration of symptoms
TB: Gradual onset (weeks to months)
- Anyone with unexplained cough ≥ 3 weeks should be evaluated for TB
Pneumonia: Acute onset (hours to days)

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9
Q

Clinical presentation - Radiological findings

A

1) Infiltrates in apical region
- Obligate aerobe –> requires oxygen –> stays at apical region, where there is higher oxygen concentration
- VS Pneumonia: Generally infects middle/lower lobes

2) Cavitary lesions

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10
Q

Latent TB - Diagnosis

A

Asymptomatic - Must be screened/tested to diagnose
Diagnostic tests:
1) Tuberculin skin test
2) Interferon gamma release assay

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11
Q

Tuberculin skin test - How it works

A

Expose patient to bacteria antigen
Positive test: If patient has prior exposure –> will mount an immune response –> results in swelling, erythema
Negative test: No prior exposure –> body does not mount immune response

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12
Q

Tuberculin skin test - Procedure

A

1) Inject 0.1 mL of PPD intradermally
2) Read after 48-72h by trained reader
3) Measure diameter of induration NOT erythema

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13
Q

Tuberculin skin test - Strengths

A

1) High sensitivity (95 - 98%)
2) Low cost
3) No need to collect blood samples

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14
Q

Tuberculin skin test - Limitations

A

1) False negative
- Occurs with immunocompromised patients –> unable to mount immune response
2) False positive
- Environmental contact with non-tuberculosis Mycobacterium
- BCG vaccination
• Most SG residents are BCG vaccinated
• MOH guidelines: Only considered positive if induration ≥ 10 mm
3) Inter-reader variability
4) No universally accepted standard for interpreting result

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15
Q

Interferon gamma release assay - Procedure

A

1) Blood collection into special tubes

2) Measures interferon-gamma released by WBCs in response to incubation with M. tuberculosis-specific antigens

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16
Q

Interferon gamma release assay - Strengths

A

1) Performance is as good as PPD test
2) No false positives with BCG vaccinated individuals
3) Minimal cross-reactivity with non-tuberculosis Mycobacteria
4) Results available within few hours

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17
Q

Interferon gamma release assay - Limitations

A

1) More expensive
2) Need for blood samples
3) False negative with immunocompromised patients

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18
Q

Latent TB - Screening

A

Indication for screening:
High risk group AND Intend to treat if positive

High risk group:

1) Children with recent TB contact
2) HIV-infected individuals
3) Patients considered for tumour necrosis factor antagonist therapy
- Highly immunosuppressive drug –> may activate latent TB
4) Dialysis
- Chronic diseases cause certain level of immunosuppression
- Frequent encounter with healthcare system –> increase risk of transmission if activate TB
5) Transplant (immunosuppressed)

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19
Q

Latent TB - Infection control

A

No special infection control procedures (not infectious)

20
Q

Antibiotic treatment of latent TB - Benefits

A

Reduce lifetime risk of progression to active TB (from ~10% to 1%)

21
Q

Antibiotic treatment of latent TB - Prior to initiation

A

1) Exclude active TB

2) Weigh risk VS benefit

22
Q

Antibiotic treatment of latent TB - Treatment regimen

A

1) Isoniazid
- Recommended, especially with pregnancy, lactation, HIV
- Must co-administer with Pyridoxine PO min 10 mg/day (prevent peripheral neuropathy)
OR
2) Rifampicin OR
- Alternative if cannot tolerate Isoniazid (usually due to hepatotoxicity)
OR
3) Rifampicin + Isoniazid
- Less common
- Must be done under DOT
- Not recommended for HIV patients

23
Q

Antibiotic treatment of latent TB - Dosing

A

Isoniazid

  • PO 5 mg/kg daily x 9 months (preferred) OR 6 months (lower efficacy); Max 300 mg/day
  • Tables available: 150mg, 300mg
  • With PO Pyridoxine min 10 mg/day

Rifampicin

  • PO 10 mg/kg daily x 4 months; Max 600 mg/day
  • Tablets available: 100mg, 300mg

Isoniazid + Rifapentine
- PO 900 mg weekly x 12 weeks

24
Q

Active TB - Diagnosis

A

Suspect based on

  • History (gradual onset)
  • Risk factors
  • Clinical presentation
  • Physical examination findings
  • Chest X-ray findings

AFB smear
- If positive, initiate treatment (don’t need to confirm with cultures)

Cultures

  • 4-8 weeks to grow & get confirmation of TB
  • Another 4-6 weeks for susceptibility results
  • Difficult to grow M. tuberculosis –> may not get positive culture
25
Q

Active TB - Infection control

A

In hospitals:

1) Airborne precautions needed (isolation)
- Negative pressure rooms
- PPE
2) Airborne precautions not needed after 2 weeks of effective treatment

In community:

1) No need to avoid household members
2) Ventilate home
3) Avoid public places, wear a mask when going out
4) Cough etiquette
5) Take TB medications

26
Q

Management of active TB in SG

A

Mandatory reporting to National Tuberculosis Registry

Singapore TB Elimination Program (STEP):

1) Promotes Directly Observed Therapy (DOT)
- Patient brought back to polyclinic / hospital TB observation unit to take medications
- May involve community outreach –> trained nurse go to patient’s home
- Ensure compliance, especially with long treatment duration
2) National Treatment Surveillance Registry
- Monitor treatment progress & outcomes of all TB patients
3) Contact investigations

27
Q

Antibiotic treatment of active TB - Benefits

A

To patient:

1) Reduce no. of replicating & persisting bacteria
2) Achieves durable cure & prevent relapse
3) Prevent development of resistance

To public health
1) Minimize transmission

28
Q

Antibiotic treatment of active TB - Initiation

A

Initiate with positive AFB smear

No need to wait for confirmation with cultures

29
Q

Antibiotic treatment of active TB - Treatment regiments

A

1) Standard 6-month treatment OR
2) Standard 9-month treatment
- Used if unlikely to tolerate Pyrazinamide e.g. due to liver disease, elderly
- Pyrazinamide can cause severe & prolonged hepatotoxicity
- VS Rifampicin, Isoniazid –> hepatotoxicity usually reversible when stopped

30
Q

Antibiotic treatment of active TB - Standard 6 month treatment

A

2 month intensive phase:

  • Rifampicin + Isoniazid + Pyrazinamide + Ethambutol / Streptomycin
  • Daily administration

4 month continuation phase

  • Rifampicin + Isoniazid
  • Daily OR 3x/week administration

Note: Only progress to continuation phase (after intensive phase) if:
1) Confirmed susceptibility to Rifampicin & Isoniazid OR
2) Negative culture (assumed susceptible)
If show resistance to either Rifampicin & Isoniazid –> multi-drug resistant TB

31
Q

Antibiotic treatment of active TB - Standard 9 month treatment

A

2 month intensive phase:

  • Rifampicin + Isoniazid + Ethambutol
  • Daily administration

7 month continuous phase:

  • Rifampicin + Isoniazid
  • Daily OR 3x/week administration

Note: Only progress to continuation phase (after intensive phase) if:
1) Confirmed susceptibility to Rifampicin & Isoniazid OR
2) Negative culture (assumed susceptible)
If show resistance to either Rifampicin & Isoniazid –> multi-drug resistant TB

32
Q

Antibiotic treatment of active TB - Dosing

A

Should all be administered at the same time
Choose lowest effective dose, based on strengths available

Rifampicin

  • PO 10 mg/kg daily OR 3x/week; Max 600 mg/dose
  • Tablets available: 100mg, 300mg

Isoniazid

  • PO 5 mg/kg daily; Max 300 mg/dose OR
  • PO 15 mg/kg 3x/week; Max 900 mg/dose
  • Tablets available: 150mg, 300mg
  • With PO Pyridoxine min 10 mg/day

Pyrazinamide

  • PO 15 - 30 mg/kg daily; Max 2 g/dose
  • Tablets available: 500mg

Ethambutol

  • PO 15 - 25 mg/kg daily; Max 1600 mg/dose
  • Tablets available: 100mg, 400mg
  • Renal dose adjustment needed

Streptomycin

  • IM 10 - 15 mg/kg daily; Max 1 g/dose
  • Vials available: 1g
  • Renal dose adjustment needed
33
Q

Monitoring hepatotoxicity - Hepatotoxic agents

A

Rifampicin, Isoniazid, Pyrazinamide

34
Q

Monitoring hepatotoxicity - Hepatotoxicity definition

A

1) ALT > 3x ULN with symptoms OR

2) ALT > 5x ULN with/without symptoms

35
Q

Monitoring hepatotoxicity - Risk factors

A

1) > 35 years
2) Females
3) Underlying liver disease
4) Concurrent alcohol use
5) HIV

36
Q

Monitoring hepatotoxicity - Patient counseling

A

Signs & symptoms of hepatotoxicity: N/V, unexplained fatigue, abdominal pain/discomfort
If present, stop treatment & see a doctor immediately

37
Q

Monitoring hepatotoxicity - LFTs monitoring (latent TB)

A

No risk factors:
Before treatment - No need to check baseline LFTs
During treatment - No need for routine monitoring of LFTs

≥ 1 risk factor:
Before treatment - Check baseline LFTs
During treatment - Check LFTs every 2-4 weeks

38
Q

Monitoring hepatotoxicity - LFTs monitoring (active TB)

A

No risk factors:
Before treatment - Check baseline LFTs
During treatment - No need for routine monitoring of LFTs

≥ 1 risk factor:
Before treatment - Check baseline LFTs
During treatment - Check LFTs every 2-4 weeks

39
Q

Monitoring hepatotoxicity - Management (latent TB)

A

1) Stop treatment immediately
2) Monitor LFTs
3) Re-challenge with Isoniazid when ALT < 2x ULN
4) If cannot tolerate Isoniazid, switch to Rifampicin x 4 months

40
Q

Monitoring hepatotoxicity - Management (active TB)

A

1) Stop ALL drugs immediately
2) Monitor LFTs
3) Re-challenge sequentially when LFTs normalize & symptoms resolve
4) If re-challenge fails, may need non-hepatotoxic regimen
- E.g. Ethambutol + Fluoroquinolone + Streptomycin

41
Q

Monitoring visual toxicity - Agents causing visual toxicity

A

Ethambutol

42
Q

Monitoring visual toxicity - Visual toxicity

A

Reduced visual acuity

Reduced red-green colour discrimination

43
Q

Monitoring visual toxicity - Monitoring parameters

A

Visual acuity tests & colour discrimination tests

44
Q

Monitoring visual toxicity - Monitoring frequency

A

At baseline for ALL patients

Monthly for patients with ANY of the following:

1) Ethambutol > 25 mg/kg
2) Ethambutol > 2 months
3) Renal insufficiency (e.g. chronic kidney disease)

45
Q

Monitoring visual toxicity - Patient counseling

A

Monitor for changes in vision

If present, stop treatment & see a doctor immediately

46
Q

Drug interactions

A

Rifampicin
- Induces CYP1A2, CYP2C9, CYP2C19, CYP3A4, P-gp

Isoniazid
- Inhibits CYP2C19, CYP2D6, CYP2E1, CYP3A4

Errors (6 decks)

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