Antimycobacterial Agents

Question 1

Isoniazid

Answer 1

Rx: Active and latent TB

MOA: inhibits synthesis of mycolic acid (need for mycobacterial cell wall)

Resistance: due to mutation of Kat G gene (lack of prodrug activation) and overexpression of Inh A protein (enzyme in mycolic acid synthesis)
MUST GIVE AT LEAST 2 ANTI-TB AGENTS

SE: hepatitis (↑ w/ age, alcohol), peripheral neuropathy (those w/ slower metabolism)

Question 2

Rifampin

Answer 2

Rx: Active TB (alternative to isoniazid in latent TB)

MOA: inhibits RNA synthesis

Resistance: point mutations in bacteria RNA polymerase gene (target of Rifampin)

SE: N/V, HA, fatigue, hepatitis (↑ w/ liver disease), red-orange color in urine, feces, sweat, tears, saliva

Strong inducer of Cytochrome P450 (can’t use in HIV pts)

Question 3

Pyrazinamide

Answer 3

Rx: Active TB

MOA: unknown; prodrug converted by bacterial pyrazinamidase; activity dependent on acidic environment

Resistance: mutation in pyrazinamidase

SE: hyperuricemia, hepatotoxicity

Always used in ComboTx

Question 4

Ethambutol

Answer 4

Rx: Active TB and MAC infections

MOA: inhibits arabinosyl transferases (mycobacterial cell wall synthesis)

Resistance: point mutations in arabinosyl transferase

SE: retrobulbar neutritis (impaired visual acuity, red-green color blindness)

Always used in ComboTx

Question 5

Streptomycin

Answer 5

Aminoglycoside
Rx: resistant TB (TB and MAC infections)

MOA: interferes w/ protein synthesis

Resistance: point mutations in ribosomal proteins

SE: ototoxicity (vertigo, hearing loss); nephrotoxicity

Question 6

Rifabutin

Answer 6

Rx: TB in HIV+ Patients (TB and MAC infections)

Greater activity against MAC infections than rifampin.

Less potent inducer of cytochrome P450 than rifampin.

Question 7

M. avium Complex (MAC) Treatment

Answer 7

ComboTx

1. Macrolide antibiotic (clarithromycin or azythromycin)
2. rifampin
3. ethambutol
4. +/- streptomycin

Question 8

Mycobacteria Leprae Treatment

Answer 8

ComboTx

1. Dapsone
2. Clofazimine
3. Rifampin

Tuberculoid: 1-2 years
Lepromatous: 5 years

Question 9

Dapsone

Answer 9

Para-amino-benzoic acid analogue
Rx: M. Leprae

MOA: inhibitor of folic acid synthesis

SE: non-hemolytic anemia; hemolytic anemia in pts w/ G6PD

Question 10

Clofazimine

Answer 10

Bacterial Dye
Rx: M. Leprae

MOA: unknown

SE: skin discoloration (red-brown to black)