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Pharmacotherapy > Tuberculosis > Flashcards

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
Q

What are the infection control measures for Latent TB pts?

A

NIL

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26
Q

What are the infection control measures for Active TB pts?

A

– 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

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27
Q

How long must airborne precautions be taken for an active TB pt?

A

Generally, airborne precautions no longer needed after 2 weeks of effective treatment

28
Q

What are some things to note prior to Latent TB tx initiation?

A
  • Exclude active TB

* Weigh risk versus benefit

29
Q

What are the treatment options for Latent TB tx?

A
  • Isoniazid Monotherapy
  • Rifampicin Monotherapy
  • Isoniazid + Rifapentine Combination therapy
30
Q

What is the dose for Isoniazid Monotherapy in Latent TB tx?

A

Dose: 5 mg/kg PO daily (max 300 mg PO daily)

31
Q

What is the duration for Isoniazid Monotherapy in Latent TB tx?

A

Duration: 9 months (preferred) or 6 months (lower efficacy)

32
Q

What are the considerations for Isoniazid Monotherapy in Latent TB tx?

A

Preferred regimen, especially in pregnancy, lactation, HIV

Co‐administer with Vit B6 pyridoxine (at least 10mg/day) to minimize neuropathy

33
Q

What is the dose for Rifampicin Monotherapy in Latent TB tx?

A

10 mg/kg PO daily (max 600mg PO daily)

34
Q

What is the duration for Rifampicin Monotherapy in Latent TB tx?

A

4 months

35
Q

What are the considerations for Rifampicin Monotherapy in Latent TB tx?

A

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
Q

What is the dose for Isoniazid + Rifapentine Combination therapy in Latent TB tx? FYI

A

900mg PO weekly

37
Q

What is the duration for Isoniazid + Rifapentine Combination therapy in Latent TB tx? FYI

A

12 weeks

38
Q

What are the considerations for Isoniazid + Rifapentine Combination therapy in Latent TB tx? FYI

A

Must be given under directly observed therapy (DOT)
Not recommended for HIV patients

*alot of monitoring to ensure compliance (not preferred)

39
Q

Why is there a need to tx active TB?

A

– 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
Q

What are some local healthcare initiatives when it comes to TB in SG?

A

– Mandatory reporting to the National Tuberculosis Registry
– Singapore TB Elimination Program (STEP)
• Promotes Directly Observed Therapy (DOT)
• National Treatment Surveillance Registry
• Contact investigations

41
Q

What is Directly Observed Therapy (DOT)?

A

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
Q

State the ROA, dose (including max per dose), and available tablet preparations for Rifampicin (RIF)

A

PO 10mg/kg daily OR
PO 10mg/kg 3x/week
Max per Dose: 600mg
Tablet: 100mg, 300mg

43
Q

State the ROA, dose (including max per dose), and available tablet preparations for Isoniazid (INH)

A

PO 5mg/kg daily up to 300mg per dose OR
PO 15mg/kg 3x/week up to 900mg per dose
Tablet: 150mg, 300mg

44
Q

State the ROA, dose (including max per dose), and available tablet preparations for Pyrazinamide (PZA)

A

PO 15‐30mg/kg daily
Max per dose: 2g
Tablet: 500mg

45
Q

State the ROA, dose (including max per dose), and available tablet preparations for Ethambutol (EMB)

A

PO 15‐25mg/kg daily
Max per dose: 1600mg
Tablet: 100mg, 400mg

*Note, renal adjustment needed

46
Q

State the ROA, dose (including max per dose), and available dose preparations for Streptomycin (STM)

A

IM 10‐15 mg/kg daily
Max per dose: 1g
Vial: 1g

*Note, renal adjustment needed

47
Q

What is the treatment regimen for active TB?

A

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
Q

Between STM and EMB, which is the preferred 1st line drug in tx of active TB?

A

EMB is preferred
- PO

*Both are viable 1st line drugs

49
Q

What are the criteria for transferring a patient from the intensive phase to the continuation phase of active TB tx?

A

Confirmed susceptibility to RIF and INH
OR
Culture negative pulmonary tuberculosis

50
Q

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?

A

Pt has MDR-TB, we cannot step down to continuation phase.

Tx the MDR-TB

51
Q

What should we do if the pt indicated for active TB tx is elderly or has liver disease?

A

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
Q

If RIF, INH and PZA all cause hepatotoxicity, why is PZA the main consideration for a patient with liver impairment?

A

PZA can caused prolonged and severe hepatotoxicity, more of a problem than RIF/INH (cause reversible hepatotoxicity)

53
Q

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?

A

Confirmed susceptibility to RIF and INH
OR
Culture negative pulmonary tuberculosis

*Same as 6month tx

54
Q

What are 4 things to note regarding administration of TB medications for active TB tx?

A

Conc-dependent kill
Administer all drugs in 1 go (meant for same infection)
OD dosing
Many DDIs –> Evaluate medications CAREFULLY

55
Q

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
A
  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
Q

What are some things to note for monitoring Active TB tx?

A

RIF, INH, PZA all cause hepatotoxicity

EMB causes visual toxicity (reduced visual acuity and red-green discrimination)

57
Q

What are the risk factors for hepatotoxicity for active TB tx?

A

Risk factors: age > 35 years, female, underlying liver disease, concurrent alcohol use, HIV

58
Q

What are some patient education pointers for both latent and active TB tx?

A

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
Q

LFT monitoring frequency for Latent TB tx for a patient w/o hepatotoxicity risk factors?

A

NIL

60
Q

LFT monitoring frequency for Latent TB tx for a patient w 1 or more hepatotoxicity risk factors?

A

Before tx: baseline LFTs

During tx: LFTs every 2-4wks

61
Q

LFT monitoring frequency for Active TB tx for a patient w/o hepatotoxicity risk factors?

A

Before tx: baseline LFTs

62
Q

LFT monitoring frequency for Active TB tx for a patient w 1 or more hepatotoxicity risk factors?

A

Before tx: baseline LFTs

During tx: LFTs every 2-4wks

63
Q

What are the definitions of hepatotoxicity while we are monitoring TB pts?

A

ALT > 3x upper limit of normal [ULN] with symptoms; OR

ALT > 5x ULN without symptoms

64
Q

What is the management plan if hepatotoxicity is detected for a Latent TB pt?

A
  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
Q

What is the management plan if hepatotoxicity is detected for an active TB pt?

A
  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
Q

What does ‘re-challenge’ refer to in TB management of hepatotoxicity?

A

Re-challenge by adding the drugs back one by one so we can identify the drug that pt cannot tolerate

67
Q

Visual acuity and color discrimination test frequency for a patient on RIPE TB tx?

A

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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