Tuberculosis Meds

Question 1

Mandel-Mantoux Test

Answer 1

• TST aka PPD
• must be read within 48-72 hours
• immunosuppressed pts (HIV, transplant, prior tb)
  
  • 5+mm = positive
• Immunocompetent pts but high risk
  
  • 10+ mm = positive
• Anybody with no known risk
  
  • 15+ mm = positive

Question 2

2-step TST testing

Answer 2

• if negative rxn = retest 1-3 weeks later
  
  • if positive = rxn = boosted due to TB infx that happened a while ago, may or may not treat LTBI
  • if negative = person most likely does NOT have TB infx
• if positive rxn = f/u for + TST and evaluate for LTBI tx

Question 3

IGRAs

Answer 3

interferon-gamma release assays → infected WBCs produce interferon-gamma (IFN-g)

• used to detect TB via blood test
• Quantiferon-TB Gold plus
  
  • measure IFN-g level in blood
• T-spot
  
  • measure of # of IFN-g producing cells (spots) – WBC
• Advantages:
  
  • unaffected by BCG vaccine or other non-TB mycobacteria
  • results <24 hours vs 3 days with TST (PPD)
• Disadvantages:
  
  • samples need to be processed in 8-30hours when WBCs are still viable
  • sensitivity may lower in immunocompromised
  • limited data for kids <5 yo; recently exposed to TB; and healthcare workers
  • more expensive

Question 4

Sputum Test and TB

Answer 4

AM sputum collections x 3 days

• can be induced by using aerosolized hypertonic saline
• sputum is then smeared on a slide and stained with an “acid-fast” procedure
• results available in a few hours
• postive result? → presumptive positive diagnosis of tb

Question 5

LTBI

Answer 5

Latent TB Infection

• TB is in the body but is encapsulated by immune system cells
• no s/sxs of TB
• Results:
  
  • TST/IGRA results = +
  • CXR = -
  • smear and cx = -
• cannot spread to others
• High Priority for tx:
  
  • HIV infected pts
  • fibrotic changes on CXR
  • organ transplant recipients
  • immunosuppressed pts
    
    • >15mg/day of prednisone for 1+ months
    • taking TNF-alpha antagonists
      
      • etanercept (Enbrel)
      • infliximab (Remicade)
      • adalimumab (Humira)
  • IV drug users
  • immigrants <5 yrs

Question 6

Mycobacterial Cell Wall

Answer 6

Two important layers:

• mycolic acid layer more superficial
• arabinogalactan layer is deep to the other layer

Question 7

Which TB drugs inhibit cell-wall synthesis

Answer 7

IPE:

Isoniazid

Pyrazinamide

Ethambutol

and TCA1 (and inhibits cofactor biosynthesis)

Question 8

Which TB drug inhibits RNA synthesis

Answer 8

Rifampin

Question 9

Which TB drug inhibits ATP synthase

Answer 9

bedaquiline (Sirturo)

Question 10

Rifamycins

Answer 10

• Rifampin (Rifadin)
  
  • SEs: nausea, anorexia
    
    • hepatotoxicity
    • discoloration of body fluids
  • DDI: 1A2, 2C9, 3A4 inducer
• Rifabutin (Mycobutin)
  
  • SEs:
    
    • neutropenia, leukopenia, thrombocytopenia
    • uveitis
    • hepatotoxicity
    • flu-like sxs
    • discoloration of body fluids
  • DDI: less than rifampin, weak inducer
• Rifapentine (Priftin)
  
  • SEs:
    
    • similar to rifampin
  • DDI:
    
    • similar to rifampin

Question 11

Isoniazid

Answer 11

• prodrug
• SEs:
  
  • hepatitis → elevation of LFTs (liver function tests)
  • neuropathy→ Should give with Vitamin B6
  • lupus-like syndrome → swollen, painful joins, fever, butterfly-shaped rashes (Milar rash)
• monitor LFTs monthly if pt has liver dz
• DDI:
  
  • 2C19 and 3A4 inhibitor (weak) → increase levels of AED and warfarin

Question 12

Pyrazinamide

Answer 12

• MOA unclear but more active in acidic pH
  
  • active against dormant or semi-dormant TB in cytoplasm
• prodrug→ pyrazinoic acid (POA)
• SEs:
  
  • hepatotoxicity
  • N/V
  • hyperuricemia → gout attack
  • rashes
• Monitoring:
  
  • LFTs with liver disease
  • uric acid levels (a good marker for compliance)→ gout problems
• DDI: allopurinol, febuxostat, probenicid (PZA antagonizes effects)

Question 13

Ethambutol

Answer 13

• SEs:
  
  • optic neuritis → irreversible blindness
  • neuropathy, headache, dizziness, confusion
  • rashes, hepatotoxicity
• Monitoring:
  
  • baseline visual acuity and color
    
    • espec in pts with renal insufficiency or therapy longer than 2 months
• DDI:
  
  • antacids reduce absorption
    
    • should separate by 4 hours

Question 14

Treatment Interruptions for TB Intensive Phase

Answer 14

• Initial phase:
  
  • 2 months with 4 drugs
• <14 days: continue tx, if not totally completed in 3 months, restart from beginning
• ≥ 14 days: restart from beginning

Question 15

Treatment Interruptions for TB in Continuation Phase

Answer 15

• Continuation phase:
  
  • ~4.5 months total of 2 drugs
• <80% of planned doses completed
  
  • < 3 months → continue treatment, if not completed in 6 months, start from beginning
  • ≥ 3 months → restart 4-drug regimen from the beginning
• ≥ 80% → additional tx may not be necessary

Question 16

Tx for Active TB

Answer 16

• Preferred tx:
  
  • intensive phase interval: (RIF, INH, PZA, EMB)
    
    • 7 days/week for 2 months
    • 5 days/week for 2 months
  • Continuation phase interval: (INH, RIF)
    
    • 7 days/week for 18 weeks (4.5 months)
    • 5 days/week for 18 weeks (4.5 months)
• Preferred alternative:
  
  • same intensive tx
  • Continuation Phase interval (INH, RIF)
    
    • 3 days/week for 18 weeks (4.5 months)
• Alternatives: can do 3days/week for 8 weeks (4 drugs) then 3 days/week for 18 weeks (2 drugs) but caution with HIV pts
  
  • ***DO NOT USE twice weekly regimens for HIV pts****

Question 17

Tx for Latent TB

Answer 17

• Once a week: INH + Rifapentine x 3 months
  
  • Not for: resistant cases, <2 yo, HIV/AIDs, Pregnancy
• Twice a week: INH x 6 months
  
  • INH x 9 months for preggos
    
    • add Vitamin B6 to prevent neuropathy
  • ****NOT for resistant cases****
• Daily: Rifampin x 4 months (not for preggos)
  
  • Rif + INH x 3 months
  • INH x 6 months
  • INH x 9 months
    
    • preferred for preggos+ Vitamin B6 and HIV/AIDS
  • *****Not for resistant cases*****

Question 18

Risk Factors of TB

Answer 18

• location and birth place
• ethnicity (Hispanic; asian; non-hispanic black)
• age = 25-65
• HIV infx
• Recently (last 2 yrs) infected with TB bacteria
• immunocompromised
• abuses of alcohol or other illegal drugs
• not treated correctly for TB in the past

Question 19

Elderly and Children TB sxs

Answer 19

• Elderly:
  
  • mental status change = most common sxs
• Children:
  
  • may present as atypical bacterial PNA due to immature cellular immunity → lower and middle lobes
  • extrapulmonary TB more common (i.e. lymph nodes, GI & GU, bone marrow, and meninges)

Question 20

Other TB drugs

Answer 20

• Cycloserine
• Ethionamide→ All the SEs
• Streptomycin
• Amikacin
• Capreomycin
• Paraaminosalicyclin
• Levo/Moxi
• Bendaquiline (Sirturo) → reserved for resistant cases, affects ATP synthesis (QT prolongation)