Mycobacterial Infections

Question 1

Goals of TB Treatment is to NEVER

Answer 1

Treat w/ single drug or add single drug to failing regimen

Question 2

Directly Observed Therapy

Answer 2

Preferred management strategy for ALL patients

Question 3

For drug-resistant TB use

Answer 3

The daily regimen & DOT

Question 4

Anti -TB 1st line Drugs

Answer 4

Ethambutol
Isoniazid
Pyrazinamide
Rifabutin
Rifampin
Rifapentine

Question 5

Anti - TB 2nd line Drugs

Answer 5

Bedaquiline 
Capreomycin
Cycloserine
Ethionamide
p-Aminosalicyclic acid
Streptomycin

Question 6

4 regimens recommended for TB (drug susceptible) treatment are

Answer 6

Initial phase: standard 4 drugs INH, PZA, EMB, RIF for 2 months (1 excludes PZA)
Continuation phase: Additional 4 months or 7 months for some

Question 7

Isoniazid: MOA

Answer 7

1) Most potent - don’t use as single agent
2) Pyridoxine synthetic analog
3) Bacteriostatic for stationary phase; Bactericidal for dividing phase
4) Intracellular bacteria

Question 8

Isoniazid: PK

Answer 8

Oral - readily absorbed
Food disrupts absorption (Carbs, aluminum antacids)
In infected tissues
Glomerular filtration as metabolites

Question 9

Isoniazid: Pt metabolism

Answer 9

1) N-acetylation & hydrolysis = inactive products
2) Slow acetylators excrete more of the parent compound = long half life
3) Rapid acetylators = short half life
4) Poor renal function = drug accumulation
5) Chronic liver disease decreases metabolism (reduce dose)

Question 10

Isoniazid: drug interactions

Answer 10

Increases blood levels of phenytoin (dilatin) & disulfiram (antabuse)

Question 11

Pyrazinamide: MOA

Answer 11

1) Pyrazine analog of Nicotinamide
2) Hydrolyzed becomes pyrazinoic acid
3) Bactericidal for dividing phase - unknown mechanism
4) Bacteria in lysosomes & macrophages

Question 12

Pyrazinamide: PK

Answer 12

1) Oral >90% bioavailability
2) GI absorption
3) Found in lung epithelial lining fluid
4) Body distribution (CSF penetration)
5) Renal issues = poor metabolism

Question 13

Issues of Pyrazinamide & Ethambutol

Answer 13

Gouty attacks

Urate retention

Question 14

Ethambutol

Answer 14

1) TB, disseminated MAC, M. kansasii infection
2) Bacteriostatic
3) Arabinosyl transferase inhibition

Question 15

Arabinosyl transferase inhibition =

Answer 15

Disrupts arabinogalactan cell wall formation

Question 16

Ethambutol: PK

Answer 16

1) Oral ~ 80% BA
2) Body distribution (CSF penetration)
3) Glomerular filtration & Tubular secretion
4) Dose 3x a week in ESRD

Question 17

Ethambutol: Issues

Answer 17

Optic neuritis

• visual acuity decreased
• hard to discriminate red & green
• reversible

Question 18

Rifamycins

Answer 18

1) Similar macrocyclic antibiotics

2)

Question 19

Rifapentine & Rifabutin are

Answer 19

Rifampin derivatives

Question 20

Rifampin inhibits

Answer 20

Gram positive growth & some gram negative

Question 21

Rifampin is bactericidal against

Answer 21

M. leprae

Question 22

Rifampin: MOA

Answer 22

1) Never as a single agent

2) RNA polymerase inhibitor

Question 23

Rifampin: PK

Answer 23

1) Absorption (decreased with food)
2) Body distribution (CSF penetration)
3) Enterohepatic cycling
4) Bile elimination into feces or urine
4) Orange color secretions

Question 24

Rifampin: drug interactions

Answer 24

Induces CYPs of other drugs: 1A2, 3A4, 2C9, 2C19 = therapeutic failure of these agents

Question 25

Rifabutin

Answer 25

1) Food has no effect
2) Less potent inducer of P450
3) Used for HIV on protease inhibitors or nonnucleoside reverse transcriptase inhibitors
4) Uveitis, skin hyperpigmentation, neutropenia

Question 26

Rifapentine

Answer 26

1) High fat meal increases AUC by 50%
2) Intermediate CYP inducing effects
3) Toxicity similar to rifampin

Question 27

Bedaquiline

Answer 27

1) Adults >18 w/ MDR TB
2) 4-5 mo half life
3) DOT
4) Food to maximize absorption
5) QT prolongation, hepatotoxicity
6) Not with rifamycins or other CYP3A4 inducers

Question 28

Drug Susceptibility Test

Answer 28

Culture is standard.

Xpert MTB/RIF assay: NAA test, 2hrs

Question 29

INH monoresistant TB

Answer 29

1) Use other 3 1st line drugs for 6 months or add FQ fot the 3 drug regimen (6 mo)

Question 30

MDR TB or RIF resistant TB

Answer 30

1) Induction: 5 drugs to which isolate is susceptible including FQ and injectable aminoglycoside
2) Continuation: treat with 4 of the drugs (remove injectable)

Question 31

Shorter MDR TB regimen

Answer 31

7 drugs given for 9-12 months

Question 32

Latent TB - INH 9 months

Answer 32

Daily:

1) HIV
2) Children 2-11 yrs old
3) Pregnant women (w/ pyridoxine/vitamin B6 supp)

2x weekly
1) pregnant women (w/ pyridoxine/vitamin B6 supp)

Question 33

Latent TB - INH 6 months

Answer 33

Daily NOT for:

1) HIV
2) Fibrotic lesions
3) Children

Question 34

Latent TB - INH +Rifapentine 3 months DOT

Answer 34

Weekly, NOT for:

1) HIV/AIDs
2) Resistant MTb
3) Pregnant
4) Children < 2 yo

Question 35

Rifamycin 4 months

Answer 35

Daily, NOT for:

1) Pt. on drugs that interact w/ rifamycins
2) Pt. with contact lenses
3) Pregnant or expect to become pregnant

Question 36

Treatment Regimens: Pregnancy

Answer 36

1) Initial: INH, RIF, EMB
2) Streptomycin contraindicated
3) PZA can be used
4) 9 months therapy when PZA not used
5) Can breastfeed
6) Vitamin B6 recommended with INH
7) MDR TB? Consult expert

Question 37

Treatment Regimens: Children/Infants

Answer 37

1) same as adults except EMB
2) Treat as soon as diagnosis is suspected
3) Disseminated TB or TB meningitis in children, treat for 9 to 12 mo

Question 38

Treatment Regimens: HIV/AIDS

Answer 38

1) Same principles as HIV negative patients
2) 6 mo daily regimen
- 2 months of INH, Rifamycin, PZA, EMB
- 4 months of INH, Rifamycin
3) treat empirically, DOT

Question 39

Treatment Regimens: Latent TB HIV/AIDS

Answer 39

INH daily for 9 months

Question 40

HIV/AIDS Drug interactions

Answer 40

Rifampin does drug interactions with PIs & NNRTIs

Use Rifabutin

Question 41

Treatment of Disseminated MAC

Answer 41

Clarithromycin or Azithromycin and ethambutol w/ or w/o rifabutin

Question 42

Prophylaxis of disseminated MAC of AIDS w/ CD4 <50

Answer 42

Azithromycin or Clarithromycin