Anti-Mycobacterial Agents

Question 1

Mycobacterium tuberculosis-Mtb causes

Answer 1

TB

Question 2

Mycobacterium leprae causes

Answer 2

leprosy

Question 3

Slow-growing, slender, rod-
shaped aerobic bacteria with a unique
lipid-rich (waxy, acid-fast)) cell wall.
May remain dormant in the host for
long periods.

Answer 3

Mycobacterium tuberculosis

Question 4

Mycobacterium tuberculosis is transmitted by

Answer 4

inhalation of airborne droplets that can remain aloft for minutes to hours

Question 5

Why are antimicrobials for TB treatment combined?

Answer 5

To decrease emergence of resistant strains.

Question 6

TB bacteria can become active if

Answer 6

immune system

doesn’t prevent growth

Question 7

Latent TB infection

Answer 7

Exposure to bacteria, but bacteria become inactive

Question 8

Latent TB symptoms

Answer 8

no symptoms or physical findings suggestive of TB

Question 9

In LTBI, respiratory smear and culture are

Answer 9

negative

Question 10

Symptoms of pulmonary TB disease

Answer 10

fever,cough, nightsweats,weight loss,fatigue,hemoptysis,
decreasedappetite

Question 11

Pulmonary TB disease respiratory specimens and culture are

Answer 11

positive

Question 12

5 Principles of Active TB Treatment

Answer 12

1. Multiple drugs MUST be used.
2. Drug sensitivity testing is mandatory.
3. Single daily dosing of drugs is preferred.
4. Prolonged therapy is necessary (generally >6 months).
5. Monitoring for patient compliance and toxicity is
   required (DOT, Directly observed therapy or VOT, Video
   Observed Treatmen

Question 13

First line agents for TB

Answer 13

Rifamycins: Rifampin (RIF), Rifabutin, Rifapentine
Isoniazid (INH)
Pyrazinamide (PZA) Ethambutol (EMB)

Question 14

Second line agents for TB

Answer 14

Streptomycin 
Amikacin 
Quinolones
(Moxifloxacin) 
Cycloserine 
P-Aminosalicyclic Acid Ethionamide

Question 15

Second line drugs used for TB treatment considered if

Answer 15

a) Resistance to first-line agents
b) Clinical failure of first-line therapy
c) Serious adverse drug reactions that limit treatment

Question 16

Initiation phase treatment of TB

Answer 16

isoniazid, rifampin, pyrazinamide and ethambutol

(the 4 first –line agents) administered for 2 months.

Question 17

Continuation phase treatment of TB

Answer 17

At two months, treatment with isoniazid and rifampin
are continued for 4 months - or 7 months w/ the
following:
• cavitation on chest X-ray
• positive acid fast bacillus smear
• positive culture

Question 18

What inhibits synthesis of mycolic acids

Answer 18

Isoniazid (INH)

Question 19

What is a pro-drug activated inside the mycobacterium

Answer 19

Isoniazid (INH)

Question 20

Isoniazid (INH) resistance

Answer 20

Mutations in katG or inhA promoter region (increased expression)

Question 21

Isoniazid is metabolized in

Answer 21

liver by acetylation

Question 22

Isoniazid ADME

Answer 22

-Oral absorption
-Aluminum containing antacids can interfere with absorption
(take on empty stomach, 2 hours from taking antacids)
- penetrates CSF

Question 23

Isoniazid is hepatotoxic so monitor

Answer 23

for signs of hepatic dysfunction/ hepatitis (LFTs)

Question 24

inhibits mycobacterial cell wall synthesis but primarily enhances activity of lipophilic drugs

Answer 24

Ethambutol (Myambutol®

Question 25

Ethambutol (Myambutol® ADME

Answer 25

-Oral absorption -Aluminum containing antacids can interfere with absorption -Hepatic metabolism

Question 26

most important toxicity associated with use of Ethambutol

Answer 26

Optic neuritis

Question 27

- The pro-drug enters M. tuberculosis by passive diffusion - Converted to pyrazinoic acid (POA) by nicotinamidase/pyrazinamidase (PZase). - Disrupts intracellular pH and membrane transport (may effect metabolism- energy production…exact MOA unresolved)

Answer 27

Pyrazinamid

Question 28

Pyrazinamid ADME

Answer 28

- Well absorbed - Wide tissue distribution, CSF - Hepatic metabolism

Question 29

Pyrazinamid ADE

Answer 29

-Liver injury (15%) with jaundice (2-3%), rarely fatal -Do not use with decreased liver function -Monitoring: LFTs

Question 30

Binds to the β-subunit of bacterial DNA-dependent RNA polymerase. Inhibits RNA synthesis

Answer 30

Rifamycins (Rifampin, Rifabutin, Rifapentine)

Question 31

Use Rifabutin instead of Rifampin in

Answer 31

HIV patients on ART therapy (to avoid drug interactions)

Question 32

causes orange staining of host secretions

Answer 32

Rifampin

Question 33

Rifampin ADME

Answer 33

- Oral administration (food/antacids decrease absorption) - Distributes to all body fluids and organs, including CNS - Induces hepatic mixed-function oxidases increasing its own metabolism as well as other drugs. (i.e. oral contraceptives) - Eliminated via feces and urine

Question 34

TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampicin

Answer 34

Multidrug-resistant TB (MDR TB)

Question 35

relatively rare type of MDR TB. XDR TB is defined as TB that is resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin)

Answer 35

Extensively drug-resistant TB (XDR TB)

Question 36

Inhibits proton pump for mycobacterial ATP | synthase

Answer 36

Bedaquiline (Sirturo®)

Question 37

approved for combination use against XDR TB

Answer 37

Pretomanid