Tuberculosis

Question 1

How many people globally have tuberculosis?

Answer 1

10 million people worldwide with active TB and 1.4 million people died from TB in 2020

Question 2

What section of the Canadian population is disproportionately affected by TB?

Answer 2

Immigrants and Indigenous people

Question 3

What age group forms the largest number of reported cases of TB?

Answer 3

Almost 20% of the people with TB are between 25 and 34

Question 4

How concerning is TB in Saskatchewan?

Answer 4

It is spreading at an alarming rate within indigenous communities

Question 5

What bacteria is responsible for the most TB?

Answer 5

Mycobacterium tuberculosis

Question 6

What are some characteristics of Mycobacterium tuberculosis?

Answer 6

Acid fast bacillus (Ziehl-Neelson stain)

Impervious to gram-staining

Relatively slow growing, doubling in 20 hours

Question 7

How is Mycobacterium tuberculosis spread in the community?

Answer 7

• Spread airbone via coughing or sneezing
• Host inhales droplet nuclei
• Close contacts (family members, coworkers, co-residents of shelters, prisons, and nursing homes (co-habitating individuals are most likely to be infected)
• With prolonged contact (risk of infection can be up to 30%)

Question 8

Which patient groups have higher incidence rates of TB?

Answer 8

• Foreign born from highly endemic areas
• Canadian Indigenous people
• Close contacts
• Homelessness
• Incarceration
• Alcoholism, Intravenous Drug Users, malnutrition
• Co-infection with HIV (accelerated decline of immunological functions)

Question 9

What are some risk factors for TB infections?

Answer 9

• Once infected with M. tuberculosis (lifetime risk of active TB is approx. 10%)
• Greatest risk is during first 2 years after infection
• Extremes of age (1-5x greater risk of active disease)
• Immunosupression (4-16x greater risk)
• HIV-infected (100x greater risk)

Question 10

What does the likelihood of M. tuberculosis transmission to a new patient depend on?

Answer 10

The likelihood of a transmission event will depend on the number of infectious droplet nuclei per volume of air and the length of time that the uninfected perosn spends breathing that air

Question 11

What are some factors that increase the probablity of M. tuberculosis transmission?

Answer 11

• Bacterial burden
• Upper lung-zone disease on CXR in source patient
• Laryngeal disease in source patient
• Amount and severity of cough in source patient
• Duration of exposure
• Crowding and poor room ventilation
• Delayed diagnosis annd/or treatment

Question 12

How does a patient get infected by M. tuberculosis for the first time?

Answer 12

Occurs by inhalation of droplet nuclei which reach alveoli

Progression to clinical disease depends on the following:
- Infecting dose (# of organisms inhaled)
- Virulence of the organism
- Cell-mediated immune response (is innate immune system of macrophages capable of controlling infection, or does that adaptive immune system need to respond)

Question 13

What is TB reactivation disease?

Answer 13

• Occurs in about 10% of cases
• Organisms within granulomas emerge and infect the apices of the lungs (low host defences)
• If untreated, the bacterial infection will destroy the lung (hypoxia, respiratory acidosis, and death)

Question 14

What are some extrapulmonary manifestations of TB?

Answer 14

• Lymphatic and pleural disease are most common
• Vertebrae, joints, GU, and meninges can also be affected
• If organism gets into blood, can cause miliary TB (medical emergency)
• Can accelerate the progression of HIV via synergistic effect

Question 15

What are some signs and symptoms associated with TB?

Answer 15

• Gradual onset
• Patients may not seek care until hemoptysis (coughing up blood)
• Weight loss, fever, cough, fatigue, nightsweats
• Frank hemoptysis
• Chest exam (dullness to percussion, rales (crackling))
• Moderate increase in WBC
• Nodular infiltrates seen under CXR

Question 16

What is the Mantoux test?

Answer 16

Also known as the TB skin test

• 5 tuberculin unit dose is injected just below the dermis
• Read size of the bump in 48-72 hours to determine if patient has been infected with TB or has an active infection

Question 17

In addition to a postive Mantoux test result, what else needs to test positive to confirm TB diagnosis?

Answer 17

Sputum culture and sensitivity (3 consecutive days of positive results)

Question 18

What are the three subpopulations of TB that cause disease?

Answer 18

1. Extracellular (rapidly dividing within protective cavities)
2. Within granulomas (semidormant, very slow replication with bursts of activity)
3. Intracellular within macrophages

Question 19

What are the best drugs for Extracellular TB?

Answer 19

Isoniazid
Rifampin
Streptomycin

Question 20

What are the best drugs for TB within granulomas?

Answer 20

Pyrazinamide
Rifampin
Isoniazid

Question 21

What are the best drugs for intracellular TB?

Answer 21

Rifampin
Isoniazid
Quinolones

Question 22

What is the first line treatment for latent TB infection?

Answer 22

Rifampin OD for 4 months

Question 23

What is the second-line treatment for latent TB infection?

Answer 23

Rifapentine and Isoniazid once weekly for 3 months

Question 24

For patients who cannot tolerate rifamycin, what drugs are used to treat latent TB infections?

Answer 24

Isoniazid daily for 9 months, if cannot be tolerated this long then try 6 months

Question 25

What are the two most important drugs for treatment of active TB infection?

Answer 25

2 main drugs are isoniazid and rifampin (used together whenever possible)

Question 26

What is the standard treatment schedule for an active TB infection?

Answer 26

Quadruple therapy (isoniazid, rifampin, pyrazinamide, ethambutol) for 2 months, followed by isoniazid and rifampin for another 4 months Drugs are dosed daily 6 month total anti-TB therapy

Question 27

How often are patients with HIV dosed for active TB infection treatment?

Answer 27

Thrice weekly

Question 28

If a patient with an active TB infection cannot tolerate isoniazid and rifampin, how long are ethambutol and pyrazinamide used to complete course?

Answer 28

2 years

Question 29

What is the mechanism of action for isoniazid in TB treatment?

Answer 29

They inhbit bacterial wall synthesis (similar effect as penicillins, but different mechanism)

Question 30

What are some dosing and administration instructions for isoniazid?

Answer 30

- Take on an empty stomach - Polymorphisms exist for its metabolism (slow acetylators = higher risk of neurotoxicity) - Elevations in serum transaminases common (12-15%, so monitor liver function)

Question 31

What are some risk factors for hepatotoxicity while on isoniazid therapy for TB?

Answer 31

- Age - Pre-existing liver dysfunction - Excess ethanol (alcohol consumption) - Pregnancy - Post-partum

Question 32

What are some risk factors for neurotoxicity while on isoniazid therapy for TB?

Answer 32

- Pyridoxine deficiency - Pregnancy - Breastfeeding - Diabetes - CKD - HIV - Seizure disorders - Substance misuse - Children

Question 33

What are some drug interactions associated with isoniazid?

Answer 33

Inhibits metabolism of phenytoin, carbemazepine, primidone, and warfarin

Question 34

What is the mechanism of action for rifampin?

Answer 34

It inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription

Question 35

How long does anti-TB treatment last without rifampin?

Answer 35

Treatment is minimum 12-18 months

Question 36

What is the cross-resistance between rifampin and other antibiotics used to treat active TB infections?

Answer 36

Rifampin resistant strains are often resistant to isoniazid

Question 37

What are some dosing and administration instructions for rifampin?

Answer 37

- Empty stomach - Usual dose is 10mg/kg

Question 38

What are some side effects associated with the use of rifampin?

Answer 38

- Rash, flu-like symptoms - GI - Gives body secretions an orange-red hue - Hepatoxicity (1%) - elevation in liver enzymes

Question 39

What are some drug interactions associated with rifampin?

Answer 39

It is a potent CYP3A4 inducer (macrolides, methadone, warfarin, steroids, phenytoin) It also interacts with oral contraceptives (increased risk of unplanned pregnancy)

Question 40

What are some characteristics of rifabutin?

Answer 40

- Fewer drug interactions than rifampin - Preferred with some antiretrovirals and immunosuppressives - Arthralgias, myalgia - Less common (hepatoxicity, neutropenia, thrombocytopenia)

Question 41

What are some characteristics of rifapentine?

Answer 41

- Longer half-life than rifampin - Rash, hematologic (anemia, lymphocytopenia, thrombocytopenia) - More hypersensitivity reactions

Question 42

What is the impact of using pyrazinamide in anti-TB quadruple therapy?

Answer 42

When used in the first 2 months, shortens duration of therapy to 6 months instead of 9 months(preferred by HCPs and patients)

Question 43

What are some side effects associated with pyrazinamide?

Answer 43

- GI, arthralgias, and increased uric acid - Hepatoxicity (major SE and dose-related)

Question 44

What are some characteristics of Ethambutol?

Answer 44

Generally bacteriostatic (not used alone, pair with other drugs to prevent resistance)

Question 45

What is a common side effect associated with the use of Ethambutol?

Answer 45

GI side effects are common (avoid concurrent use of antacids)

Question 46

What is a serious side effect associated with ethambutol?

Answer 46

Retrobulbar neuritis (decreased visual acuity or inability to see green or both) Need regular eye exams to monitor for this side effect

Question 47

What is the role of fluoroquinolones in anti-TB therapy?

Answer 47

Levoflox. and moxiflox. are used as second line alternatives when first line options are d/c (due to hepatoxicity, neurotox., etc.)

Question 48

What are some side effects associated with the use of fluoroquinolones in anti-TB therapy?

Answer 48

Common: - Nausea - Headache - Diarrhea - Dizziness - Insomnia Serious: - Tendinopathy - QT prolongation - Blood glucose alternations

Question 49

What are some second-line agents used for anti-TB therapy?

Answer 49

- Streptomycin - P-aminosalicylic acid - Cycloserine - Ethionamide - Clofazamine - Quinolones (levoflox. and moxiflox.)

Question 50

What is the BCG vaccine?

Answer 50

Bacille Calmette-Guerin Vaccine - Contains an attenuated, hybridized live strain of M. bovis - Low efficacy rates, but still given to vulnerable populations - Can prevent severe forms of TB in children

Question 51

What is the main organisation that handles TB directly in Saskatchewan?

Answer 51

TB Prevention and Control Saskatchewan (TBPC SK) They have a head office in Saskatoon, and offices in Regina and PA. They also have mobile clinical and provide telehealth services

Question 52

What is the division of scope between TB pharmacy and community pharmacies?

Answer 52

TB pharmacy: - TB meds + relevant adverse effect management, check for interactions, efficacy, and safety Community pharmacy: - Directly observed therapy, manage new interactions (Rx and OTC), and report

Question 53

Review slide 42 for a treatment guideline for how TB is managed in Saskatchewan

Question 54

What is the interaction between rifamycins and hormonal birth control?

Answer 54

TB drug: Rifampin, rifapentine, rifabutin All of the above drugs reduce efficacy of hormonal birth control (use condom during therapy)

Question 55

What is often done to resolve drug interactions with rifampin?

Answer 55

Because rifampin is such a potent enzyme inducer, doses of the victim drugs are often increased to ensure therapeutic benefit

Question 56

Review slide 45 for common drug interactions with isoniazid

Question 57

Review slide 46 for common adverse effects associated with anti-TB therapy

Question 58

What are some patient monitoring tips for anti-TB therapy?

Answer 58

- Complete initial physical to determine baseline to which future readings will be compared against (ex. weight, visual acuity, colour vision, CXR, lab work) - Sputum (every 1-2 weeks until 2 consecutive negatives and repeat monthly until 2 consecutive negatives in 2-3 months) - Drug sensitivity testing - Adherence (directly observing therapy)