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Tuberculosis Flashcards

1
Q

What is the causative organism of TB?

A

Mycobacterium tuberculosis

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2
Q

What are the characteristics of Mycobacterium tuberculosis?

A

Obligate aerobic, slow‐growing, acid‐fact bacilli

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3
Q

What is the pathophysiology of TB?

A

98% due to airborne transmission

  • If consumed by macrophages –> no infection
  • Successful cellular immunity (T Cells) –> Latent infection
  • Bad luck/immunocompromised –> Active TB
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4
Q

What is the epidemiology of TB?

A

~50% in foreign‐born individuals
~2/3 cases in patients > 50 years
#5 cause of CAP (Any patient in Singapore with unexplained cough ≥ 3 weeks should be
evaluated for tuberculosis)

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5
Q

What are the risk factors for latent and active TB?

A

Living in urban areas
Residents of prisons, homeless shelters, nursing homes
Close contact with pulmonary tuberculosis patients
Co‐infection with HIV

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6
Q

What are the risk factors for active TB?

A 
Children < 2 years
Elderly > 65 years
Malnutrition
Immunosuppression
Co‐infection with HIV
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7
Q

What is the biggest risk factor for TB?

A

Most impt risk factor is co-infection with HIV

  • high risk behavior that predisposes to both HIV and TB
  • immunosuppression
  • predisposes to both latent and progression from latent -> active TB
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8
Q

How does TB present clinically?

A 
Primarily pulmonary infection (extra-pulmonary possible)
– Weight loss
– Fatigue
– Productive cough
– Fever
– Night sweats*
– Hemoptysis*

*Classic sx

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9
Q

What are some radiological findings that implicate TB?

A

– Infiltrates in the apical* region
– Cavitary lesions

*(apical - upper lobe) –> obligate aerobe prefers higher oxgyen conc in upper lobe

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10
Q

What is the difference between TB and CAP in terms of symptoms?

A

Duration:
TB – gradual onset (over weeks – months)
CAP ‐ acute onset (over hours – days)

Radiological:
TB: Apical lobes
CAP: Usually middle/lower lobe infiltrates

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11
Q

What is the patient group indicated for latent TB screening?

A

– High‐risk group AND Intent to treat if positive
• Children with recent TB contact
• HIV‐infected individuals
• Patients considered for tumor necrosis factor antagonist therapy
• Dialysis patients
• Transplant patients

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12
Q

Why is it necessary to screen for latent TB?

A

Treat TB before progression to active TB

– Treatment reduces the lifetime risk of progression to active TB from ~10% to ~1%

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13
Q

What are the 2 diagnosis methods for TB?

A

Tuberculin Skin test (PPD)

IFN-gamma assay

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14
Q

What is the procedure for the Tuberculin Skin test? FYI

A

Inject 0.1mL of PPD intradermally
Read after 48‐72 hours by a trained reader
Read the diameter of induration (not area of redness)

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15
Q

What is the procedure for the IFN-gamma assay? FYI

A

Blood collection into special tubes

Measures the interferon‐gamma released by WBCs in response to incubation with M. tuberculosis (specific antigens)

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16
Q

Strengths of the Tuberculin Skin Test?

A

High sensitivity (95‐98%)
Low cost
No need to collect blood samples

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17
Q

Limitations of the Tuberculin Skin Test?

A

False negative: immunosuppressed
False positive: environmental contact with non‐tuberculous mycobacteria, BCG vaccination
No universally accepted standard for interpreting results
Inter‐reader variability

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18
Q

Strengths of the IFN-gamma assay?

A 
Performance is as good as PPD
No false positive in BCG‐vaccinated
individuals
Minimal cross‐reactivity with nontuberculous
mycobacteria
Results available within few hours
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19
Q

Limitations of the IFN-gamma assay?

A

More expensive
Need for blood samples
False negative: immunosuppressed

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20
Q

Explain why immunosuppressed individuals are likely to give a false negative for TB diagnostic tests.

A

No immune reaction to test (always negative) = false negative

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21
Q

Explain the relevance of Tuberculin Skin Test in the local SG context

A

Most Singapore residents are BCG‐vaccinated:
positive PPD ≥ 10 mm

*Diff from US CDC guidelines

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22
Q

How is TB clinically diagnosed?

A

Hx
Risk factors (immune/nutritional status, age, living conditions)
Clinical presentation (night sweats, persistent cough >3 wks, hemoptysis)
Physical exam findings
Chest X-ray findings
AFB smear (if positive, initiate tx)

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23
Q

What is the expected culture time for TB?

A

4-8wks for growth and confirmation of TB

Additional 4-6wks for drug susceptibility results

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24
Q

Is there a need to wait for culture results before initiating TB tx?

A

No. The cultures would take too long.

Look at consistent clinical sx + radiological exam + +ve AFB smear to diagnose

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25
What are the infection control measures for Latent TB pts?
NIL
26
What are the infection control measures for Active TB pts?
– In hospitals: need airborne precautions • Negative pressure rooms • Personal protective equipment (PPE) (i.e. gowns, N95 mask) – In community: no need to avoid household members (already exposed) • Take TB medications, practice cough etiquette, ventilate homes
27
How long must airborne precautions be taken for an active TB pt?
Generally, airborne precautions no longer needed after 2 weeks of effective treatment
28
What are some things to note prior to Latent TB tx initiation?
* Exclude active TB | * Weigh risk versus benefit
29
What are the treatment options for Latent TB tx?
- Isoniazid Monotherapy - Rifampicin Monotherapy - Isoniazid + Rifapentine Combination therapy
30
What is the dose for Isoniazid Monotherapy in Latent TB tx?
Dose: 5 mg/kg PO daily (max 300 mg PO daily)
31
What is the duration for Isoniazid Monotherapy in Latent TB tx?
Duration: 9 months (preferred) or 6 months (lower efficacy)
32
What are the considerations for Isoniazid Monotherapy in Latent TB tx?
Preferred regimen, especially in pregnancy, lactation, HIV | Co‐administer with Vit B6 pyridoxine (at least 10mg/day) to minimize neuropathy
33
What is the dose for Rifampicin Monotherapy in Latent TB tx?
10 mg/kg PO daily (max 600mg PO daily)
34
What is the duration for Rifampicin Monotherapy in Latent TB tx?
4 months
35
What are the considerations for Rifampicin Monotherapy in Latent TB tx?
Alternative in patients who cannot tolerate isoniazid i.e. due to hepatotoxicity *hepatotoxicity for isoniazid --> may not mean hepatotoxicity for rifampicin (no cross-toxicity)
36
What is the dose for Isoniazid + Rifapentine Combination therapy in Latent TB tx? FYI
900mg PO weekly
37
What is the duration for Isoniazid + Rifapentine Combination therapy in Latent TB tx? FYI
12 weeks
38
What are the considerations for Isoniazid + Rifapentine Combination therapy in Latent TB tx? FYI
Must be given under directly observed therapy (DOT) Not recommended for HIV patients *alot of monitoring to ensure compliance (not preferred)
39
Why is there a need to tx active TB?
– Benefits the patient • Reduces the number of replicating and persisting bacteria • Achieves durable cure and prevents relapse • Prevents development of resistance – Benefits public health • Minimizes transmission to others
40
What are some local healthcare initiatives when it comes to TB in SG?
– Mandatory reporting to the National Tuberculosis Registry – Singapore TB Elimination Program (STEP) • Promotes Directly Observed Therapy (DOT) • National Treatment Surveillance Registry • Contact investigations
41
What is Directly Observed Therapy (DOT)?
Coming back to polyclinic/hospital TB observation unit daily to take meds - Community outreach possible i.e. send nurses to ensure pt take meds - DOT must be done by HPs (cannot get family members to monitor)
42
State the ROA, dose (including max per dose), and available tablet preparations for Rifampicin (RIF)
PO 10mg/kg daily OR PO 10mg/kg 3x/week Max per Dose: 600mg Tablet: 100mg, 300mg
43
State the ROA, dose (including max per dose), and available tablet preparations for Isoniazid (INH)
PO 5mg/kg daily up to 300mg per dose OR PO 15mg/kg 3x/week up to 900mg per dose Tablet: 150mg, 300mg
44
State the ROA, dose (including max per dose), and available tablet preparations for Pyrazinamide (PZA)
PO 15‐30mg/kg daily Max per dose: 2g Tablet: 500mg
45
State the ROA, dose (including max per dose), and available tablet preparations for Ethambutol (EMB)
PO 15‐25mg/kg daily Max per dose: 1600mg Tablet: 100mg, 400mg *Note, renal adjustment needed
46
State the ROA, dose (including max per dose), and available dose preparations for Streptomycin (STM)
IM 10‐15 mg/kg daily Max per dose: 1g Vial: 1g *Note, renal adjustment needed
47
What is the treatment regimen for active TB?
6 month duration 1. Intensive phase (2months) with daily administration of RIPE/S 2. Continuation phase (4months) with daily/3x per wk of RIF + INH
48
Between STM and EMB, which is the preferred 1st line drug in tx of active TB?
EMB is preferred - PO *Both are viable 1st line drugs
49
What are the criteria for transferring a patient from the intensive phase to the continuation phase of active TB tx?
Confirmed susceptibility to RIF and INH OR Culture negative pulmonary tuberculosis
50
What should we do if the patient shows resistance to either one of RIF or INH after 2 months of intensive phase tx for active TB?
Pt has MDR-TB, we cannot step down to continuation phase. | Tx the MDR-TB
51
What should we do if the pt indicated for active TB tx is elderly or has liver disease?
Due to pt being unlikely to tolerate PZA, provide 9 month tx duration 1. Intensive phase (2months) with daily administration of RIF + INF + EMB 2. Continuation phase (7months) with daily/3x per wk of RIF + INH
52
If RIF, INH and PZA all cause hepatotoxicity, why is PZA the main consideration for a patient with liver impairment?
PZA can caused prolonged and severe hepatotoxicity, more of a problem than RIF/INH (cause reversible hepatotoxicity)
53
What are the criteria for transferring a patient from the intensive phase to the continuation phase of active TB tx for a patient undergoing the 9month tx?
Confirmed susceptibility to RIF and INH OR Culture negative pulmonary tuberculosis *Same as 6month tx
54
What are 4 things to note regarding administration of TB medications for active TB tx?
Conc-dependent kill Administer all drugs in 1 go (meant for same infection) OD dosing Many DDIs --> Evaluate medications CAREFULLY
55
R.R. is a 54-year-old male with weight loss and hemoptysis at home. He is found to have a positive sputum AFB smear in the hospital. His weight is 72kg and all labs are normal. Which ONE of the following is the MOST appropriate treatment? - Wait for final sputum culture because a positive AFB smear may be a false positive - Start INH 300mg PO OM + pyridoxine 50mg PO OM - Start RIF 600mg OM + INH 300mg PO OM + PZA 1500mg PO OM + EMB 1200mg PO OM - Start RIF 600mg OM + INH 300mg PO OM + PZA 1500mg PO OM + EMB 1200mg PO OM + pyridoxine 50mg PO OM - Start RIF 600mg OM + INH 300mg PO OM + PZA 1500mg PO OM + EMB 1600mg PO OM + pyridoxine 50mg PO OM
1. Look at RIF (10mg/kg) and INH (5mg/kg) --> adult pts typically will get max doses --> RIF 600 and INH 300 2. pt has active TB --> RIPE 3. For PZA and EMB: - use min-max range to multiply by pt weight --> EMB range is 1080 - 1800mg - use the lowest effective dose for tablets within the range --> pick 1200mg (three 400mg tabs) - abit of rounding involved + tablet selection = wide dose range - conc dependent killing doesnt mean higher conc used -> balance w toxicity (also conc dependent) 4. Pyridoxine always to be given with INH (no exception)
56
What are some things to note for monitoring Active TB tx?
RIF, INH, PZA all cause hepatotoxicity | EMB causes visual toxicity (reduced visual acuity and red-green discrimination)
57
What are the risk factors for hepatotoxicity for active TB tx?
Risk factors: age > 35 years, female, underlying liver disease, concurrent alcohol use, HIV
58
What are some patient education pointers for both latent and active TB tx?
Symptoms of hepatotoxicity (i.e. nausea, vomiting, unexplained fatigue, abdominal discomfort or pain) – If present, stop treatment and see a doctor immediately ``` Active only (EMB): stop TB treatment and see a doctor immediately if they experience changes in vision ```
59
LFT monitoring frequency for Latent TB tx for a patient w/o hepatotoxicity risk factors?
NIL
60
LFT monitoring frequency for Latent TB tx for a patient w 1 or more hepatotoxicity risk factors?
Before tx: baseline LFTs | During tx: LFTs every 2-4wks
61
LFT monitoring frequency for Active TB tx for a patient w/o hepatotoxicity risk factors?
Before tx: baseline LFTs
62
LFT monitoring frequency for Active TB tx for a patient w 1 or more hepatotoxicity risk factors?
Before tx: baseline LFTs | During tx: LFTs every 2-4wks
63
What are the definitions of hepatotoxicity while we are monitoring TB pts?
ALT > 3x upper limit of normal [ULN] with symptoms; OR | ALT > 5x ULN without symptoms
64
What is the management plan if hepatotoxicity is detected for a Latent TB pt?
1. Stop treatment immediately 2. Monitor LFTs 3. Re‐challenge with INH when ALT improves to < 2x ULN - If patient can’t tolerate INH, switch to RIF x 4 months - If both INF and RIF intolerable, cease tx
65
What is the management plan if hepatotoxicity is detected for an active TB pt?
1. Stop treatment immediately 2. Monitor LFTs 3. Re‐challenge sequentially when LFTs normalized and symptoms resolved - If re‐challenge fails, may need non-hepatotoxic regimen (e.g. EMB + FQ + STM)
66
What does 're-challenge' refer to in TB management of hepatotoxicity?
Re-challenge by adding the drugs back one by one so we can identify the drug that pt cannot tolerate
67
Visual acuity and color discrimination test frequency for a patient on RIPE TB tx?
Baseline for all pts Monthly monitoring if any of the following: • Taking doses > 25 mg/kg • Taking ethambutol for more than 2 months • Has renal insufficiency (e.g. chronic kidney disease)

Pharmacotherapy (10 decks)

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