Mycobacteria

Question 1

Properties of mycobacteria

Answer 1

• aerobic, non-motile
• slowly replicating
• may lie dormant
• intracellular pathogens
• multi-laminate cell wall
• thicker cell wall
• hydrophobic mycolic acid cell wall

Question 2

M. TB

Answer 2

mainly infects macrophages. prone to resistance. multiple agents used to treat (can last months to years)

Question 3

First line agents for TB

Answer 3

Isoniazid
Rifamycins
Ethambutol
Pyranzinamide
Streptomycin

Question 4

Second line for TB

Answer 4

Moxifloxacin
ethionamide
amino salicylic acid
cycloserine
amikacin
caperomycin
linezolid
bedaquiline

Question 5

components of multi-laminate cell wall

Answer 5

glycolipids, mycolic acids, arabinogalactan, peptidoglycan

Question 6

Isoniazid MoA

Answer 6

Bactericidial:

inhibits synthesis of mycolic acids (for cell wall)

Question 7

Clinical application of Isoniazid

Answer 7

first line. treatment for latent infections - less active against other mycobacteria

Question 8

PK of isoniazid

Answer 8

hepatic clearance. short half life 1h. reduces levels of phenytoin

Question 9

Rifamycin MoA

Answer 9

bacteriacidal (lots of resistance if used alone):

inhibits DNA dependent RNA polymerase - block production of RNA

Question 10

clinical applications of rifamycin

Answer 10

first line for TB. also used for atypical mycobacterial infections. meningococcal and staph infections.

Question 11

PK of rifamycin

Answer 11

Hepatic clearance (t1/2=3.5h). induces CYP450. 
AE: TURNS BODY FLUID ORANGE; blood problems, flu like symptoms for intermittent dosing

Question 12

Pyrazinamide MoA

Answer 12

Bacteriostatic in TB. may also be bactericidal in dividing organisms.
it is converted to active pyrazinoic acid under acidic conditions in macrophage lysosomes.

Question 13

Pyrazinamide clinical application

Answer 13

“sterilizing agent” - first 2 months of therapy to shorten duration to 6 months

Question 14

PK Pyrazinamide

Answer 14

Hepatic clearance. Long half life (9h) but metabolites are renally cleared so decrease to 3 doses Qwk if CrCl

Question 15

Ethambutol MoA

Answer 15

Bacteriostatic:

inhibits mycobacterial arabinosyl transferase (polymerization reaction of arabinoglycan - cell wall)

Question 16

Ethambutol clinical application

Answer 16

4-drug initial combination until sensitivities are know. also other mycobacterial infections (atypical)

Question 17

PK Ethambutol

Answer 17

dose changed with renal failure- mixed clearance

AE: Retrobulbar neuritis.

Question 18

Streptomycin MoA

Answer 18

Bactericidial:

prevents bacterial protein synthesis by binding to 30s ribosomal subunit.

Question 19

Streptomycin clinical application

Answer 19

Injectable drug for drug resistant strains of TB

Question 20

PK of streptomycin

Answer 20

IM/IV. renal clearance. 2.5h half life.

AE: nephrotoxicity, ototoxicity. Toxicities are dose related and increase with age.`