TB Flashcards

1
Q

What is the treatment for latent TB?

A

Diagnosis

  • Mantoux
  • IGRA

Tx

  • Isoniazid + rifapentin weekly for 3 weeks OR
  • Rifampin daily for 4 moths OR
  • Isoniazid + rifampin daily for 3 months

OR
Isoniazid daily for 6 or 9 months

4 months of rifampicin = 9 months of isoniazid = 3 months of isoniazid + rifampicin

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2
Q

Treatment for active TB

A

Intensive Phase:
Rifampicin + Isoniazid + Pyrazinamide + Ethambutol for 2 months

Continuation Phase
Rifampicin + Isoniazid for 4 months

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3
Q

How does mycobacterium tuberculosis survive?

A

M. tuberculosis survives within macrophages because of the inhibition of both phagosome maturation and phagolysosome fusion

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4
Q

The cellular immune response in TB

A

Th1 cell activation
Macrophage activation and bacterial killing
Granulomatous inflammation and tissue destruction - IFNy activated macrophages secrete TNF a

Granuloma limits the spread of infection

Typically affect upper lobes of the lungs

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5
Q

What is the mantoux test

A

Tests cell-mediated immunity against M. tuberculosis through delayed hypersensitivity reaction (type IV HSR) mounted by T cells

Specificity compromised by previous BCG and exposure to non-TB mycobacterium

False Negatives

  • Sarcoidosis
  • Immunosuppressed state
  • Recent TB infection within 6-8 weeks
  • Recent live virus vaccine
  • Disseminated TB
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6
Q

What is the IGRA

A
  • Tests cell-mediated immunity against M. tuberculosis- specific antigens by measuring the amount of IFN-γ released by T cells
  • Advantage over mantoux is that antigens used are specific to TB and not present in BCG or the majority of non-tuberculosis myocbateria.
  • Positive test indicates active TB or latent TB;
  • Negative; Indeterminate, and commonly seen in: Immunosuppressed states, children < 5yo
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7
Q

Can IGRA or Mantoux differentiate between acute or latent TB?

A

○ Both the tests are unable to differentiate between active and latent TB
○ Neither TST or IGRA differentiate latent or active disease, new infection/reinfection and have a poor predictive value for who will develop active disease
○ Both perform less well in immunocompromised patient
○ Test at least 8 weeks since last exposure
Target testing to those at high risk of developing TB (i.e. test those you will treat)

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8
Q

What does drug resistant TB mean?

A

The term “drug-resistant TB” refers to cases of TB caused by an isolate of M. tuberculosis that is resistant to one of the first-line anti-TB drugs: isoniazid, rifampicin, pyrazinamide, ethambutol, or streptomycin.

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9
Q

What does mutli-drug resistant TB mean?

A

The term “multidrug-resistant TB” (MDR-TB) refers to an isolate of M. tuberculosis that is resistant to at least isoniazid AND rifampicin and possibly additional chemotherapeutic agents.

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10
Q

What does pre-extensively drug resistant TB mean?

A

The term “pre-extensively drug-resistant TB” (pre-XDR-TB) refers to an isolate of M. tuberculosis that is resistant to isoniazid and rifampcin as well as fluoroquinolones (levofloxacin or moxifloxacin)

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11
Q

What does extensively drug resistant TB mean?

A

The term “extensively drug-resistant TB” (XDR-TB) refers to an isolate of M. tuberculosis that is resistant to at least isoniazid, rifampicin, and any fluoroquinolone and at least 1/3 injectable drugs (Kanamycin, capreomycin, amikacin)

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12
Q

Risk factors for drug resistant TB

A
  • Previous treatments
  • Contact with MDR-TB or residence in a high burden centre
  • 60-70% have no history of prior treatment
  • Patients with history of TB (current or past)
  • Persistent or progressive clinical and/or radiographic findings while on anti-TB therapy
  • Lack of conversion of cultures to negative during first 3 months of anti TB therapy
  • Incomplete adherence to prescribed anti TB therapy
  • Lack of directly observed therapy or poorly supervised anti TB therapy
  • Documented treatment failure or relapse
  • Hx of inappropriate treatment regimen

Patient without prior history of TB

  • Exposure to an individual with known or suspected drug resistant TB
  • Residence in or travel to region with high prevalence of drug resistnat TB
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13
Q

Risk factors for progression to active TB

A
Highest Risk 
- HIV 
- Transplant 
Silicosis
- Chronic renal failure
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14
Q

In terms of TB drugs, what is the extent of activity for

  • prevention of resistance
  • Early bactericidal activity
A
Prevention of resistance 
From HIGH to LOW
- Isoniazid 
- Rifampicin
- Ethambutol 
- Streptomycin 
- Pyrazinamide

Early bactericidal activity - high to low

  • Isoniazid
  • Ethambutol
  • Rifampicin
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15
Q

What are the 1st and 2nd line TB medications?

A

1st Line

  • Rifampicin
  • Isoniazid
  • Pyrazinamide
  • Ethambutol

2nd Line

(a) Aminoglycosides
- Streptomycin
- Amikacin
(b) Fluoroquinolones
- Levofloxacin
- Moxifloxacin
(c) Ethionamide
(d) Linezolid

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16
Q

MOA of rifampicin and SE

A
  • MOA: inhibits bacterial DNA-dependent RNA polymerase → prevention of transcription (mRNA synthesis) → inhibition of bacterial protein synthesis → cell death (bactericidal effect)
  • SE: drug interactions (cytochrome P450 induction), hepatitis, hypersensitivity, orange discolouration of body fluids (urine, tears)

The 6 Rs of Rifampin: Red or organge urine, RNA polymerase Repression, Ramping up cytochrome P450 activity and Rapid Resistance if used alone

Rifampin really amplifies (induces) cytochrome P450 but rifabutin does not

17
Q

Isoniazid MOA and SE

A
  • MOA: prodrug and needs to be converted into its active metabolite by bacterial catalase peroxidase (encoded by KatG). Prevents cell wall synthesis by inhibiting the synthesis of mycolic acid
  • SE: hepatitis, rash, peripheral neuropathy (due to vitamin B6 deficiency, prevented with pyidoxine)
  • The only drug that can be used as monoprophylaxis against TB

INH is Not Healthy In Neurons and Hepatocytes

Neurotoxicity may be prevented by supplementing with pyridoxine

18
Q

MOA and SE of pyrazinamide

A
  • MOA:
    Not completely understood
    Prodrug: converted into active form pyrazinoic acid, most effective at acidic pH
    Bactericidal effect

SE: hepatitis, skin, polyarthralgia, gout

19
Q

MOA and SE of ethambutol?

A
  • MOA: inhibits arabinosyltransferase → ↓ carbohydrate polymerization → prevention of myobacterial cell wall synthesis (bacteriostatic effect)
  • SE: optic neuropathy

EYEthambutol: Ethambutol causes optic neuropathy

20
Q

Which TB medications causes hepatitis?

A

Pyrazinamide > Isoniazid&raquo_space; Rifampicin

ALT:

  • 2-5 x ULN and asymptomatic – monitor closely
  • > 5 x ULN or >3x ULN with symptoms – stop
  • If can’t safely stop then use: Amikacin, E, Moxi
  • Once ALT near baseline restart with drug challenge
  • Up to 75% of patients will tolerate re-introduction of isoniazid and rifampicin
21
Q

How does rifampin and isoniazid affect cytochrome P450?

A

Rifampin and isoniazid alter the efficacy of drugs metabolised by cytochrome P450 especially protease inhibitors, NNRTis, OCP, warfarin, sulfonylureas

22
Q

Primary vs secondary drug resistance

A
  • Primary drug resistance is said to occur in a patient who has never received anti-TB therapy.
  • Secondary drug resistance refers to the development of resistance during or following chemotherapy in patients who had previously had drug-susceptible TB - selection of drug resistant mutants by inadequate treatment
23
Q

Treatment for TB meningitis

A

isoniazid, rifampicin, pyrazinamide, moxifloxacin– moxifloxacin better CSF penetration than ethambutol

24
Q

What is the treatment for Mycobacterium avium infection?

A

Azithromycin/Clarithromycin +
Ethambutol +
Rifampicin/Rifabutin

25
Q

Treatment of MDR-TB

A

Group A: include all 3 medications

  • Levofloxacin/moxifloxacin
  • Bedaquiline: target ATP synthase
  • Linezolid

Group B: add both medications

  • Clofazimine
  • Cycloserine

Group C: add to complete the regimen and when medicines from Group A and B cannot be used

  • Ethambutol
  • elamanid
  • Pyrazinamide
  • Meropenem
  • Amikacin
  • Ethionamide
  • P-aminosalicyclic acid