Mycobacterium Tuberculosis

Question 1

Exposure to TB can lead to either

Answer 1

1) Active TB: Symptomatic, Contagious
OR
2) Latent TB infection (LTBI)

Question 2

Streptomycin

Answer 2

Nephrotoxicity
Ototoxicity

• Avoid other ototoxic/nephrotoxic drugs
• CI: pregnancy

Monitor monthly: auditory, renal function, electrolytes

DOSE: 15 mg/kg - 1000 mg IM/IV daily

Question 3

Preferred Regimen for treating ACTIVE TB

Answer 3

For the first EIGHT weeks (2 months) = 4 drugs

• Isoniazid
• Rifampin
• Pyrazinamide
• Ethambutol

Then, for 18 weeks (4.5 months): Isoniazid and rifampin

Question 4

TB Drugs

Answer 4

RIPES
* All bactericidal except for Ethambutol

R- rifampin (Rifadin) - EMPTY stomach
I- isoniazid (INH) - EMPTY stomach
P- pyrazinamide
E-ethambutol (Myambutol): Bacteriostatic (mainly used to inhibit the development of resistant mutants).
S- streptomycin

Question 5

Mode of transmission

Answer 5

Air droplets; cough/close proximity

Question 6

Ethambutol

Answer 6

Optic neuritis: test color vision and visual acuity monthly if > 15 mg/kg/day.

Caution in kidney disease; monitor in renal impairment.

Increases uric acid

DOSE: 15-25 mg/kg - 2500 mg PO daily
- give ethambutol 4 hour before aluminum-containing antacids, sucralfate, or buffered didanosine.

Question 7

Rifamate

Answer 7

Isoniazid + Rifampin = Rifamate

*take daily on an EMPTY stomach

Question 8

Treatment of Latent TB infection

Answer 8

Patients with latent TB have NO symptoms (they do not feel sick). They are infected with M. tuberculosis, nut do not have TB disease are are NOT contagious.

The only sign is a POSITIVE REACTION to the skin test (TST or PPD). But 1 in 10 may develop active TB if they are not treated.

TREATMENT of Latent TB:
Isoniazid 300 mg daily for 9 months
Rifampin 10 mg/kg (600 mg MAX) daily for 4 months
Isoniazid and Rifampin daily for 3 months
INH and rifapentin weekly for 3 months (12 doses).

Question 9

What is BCG?

Answer 9

BCG = Bacillus of Calmette and Guerin

BCG is a vaccine against TB that is given in countries with a high prevalence of TB.

Receiving BCG vaccine will make the individual have a positive TB skin test (+PPD), but it might wear off after years just like any vaccine.

Not routinely given in the USA due to causing patients to be +PPD; will not be able to utilize PPD test to detect latent or active TB.

Question 10

What is a positive result?

Answer 10

Significance depends on the individual & size of the skin reaction.

The reaction site is measured in millimeters of induration (hardness) at the injection site between 48-72 hours.

5 mm (small reaction) is considered to be positive if the person has low immunity (e.g., HIV, steroid therapy), or at high risk for TB infection (close contact with a person who has active TB).

10 mm: DM, CKD, healthcare workers

15 mm or greater: POSITIVE for ALL.

Question 11

Rifater:

Answer 11

Isoniazid + Rifampin + Pyrazinamide = Rifater
- dose is weight dependent

• take daily on an EMPTY stomach

Question 12

Isoniazid (INH)

Answer 12

HEPATOTOCITY - monitor LFTs periodically. Tell patents to report fatigue, N/V, dark urine.

• D/c if AST >3x upper limit with s/sx of toxicity.
• D/c if AST >5x with no s/sx of toxicity.

DRUG INTERACTION - P450 1A2, 2C9 inhibitor, Theophylline, warfarin, phenytoin.

PERIPHERAL NEUROPATHY:

• Prevention: pyridoxine (Vit. B6) 10-50 mg PO daily
• Treatment: pyridoxine (Vit. B6) 50-200 mg PO daily.

DOSE: 5 mg/kg - 300 mg PO daily

FORMULATIONS: syrup, tablets (100, 300 mg), IV

Question 13

Rifampin

Answer 13

HEPATOTOXICITY (LFT)/ renal
Fever, rash, flu-like illness, GI upset
Thrombocytopenia (CBC): increase bleeding

Rifampin is an inducer of CYP 1A2, 2C9, 3A4

• decrease efficacy of oral contraceptives
• decrease INR with warfarin

Avoid Protease inhibitors; Increase risk of hepatotoxicity

Colors body red/orange/ discolor contact lenses.

Dose: 10 mg/kg - 600 mg PO/IV daily on EMPTY STOMACH (concentration decrease if taken with food).

FORMULATIONs: Capsules (150, 300 mg ), Suspension, IV

Question 14

Newer Medications for TB: Pretomanid

Answer 14

Indication: as part of a combo regimen with bedaquiline and linezolid for the treatment of adults with PULMONARY EXTENSIVELY DRUG RESISTANT (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).

DOSE: must be administered only as part of a regimen in combination with bedaquiline and linezolid.
200 mg PO daily with FOOD x 26 weeks.

Swallow tablet whole w/ water for 26 weeks

Question 15

Rifapentine (Priftin)

Answer 15

Long-acting derivative of rifampin.

ADRs: hepatotoxicity, thrombocytopenia, hyperuricemia, orange-brown discoloration of urine, contact lenses.

Question 16

Latent TB treatment (Positive TST, CXR negative)

Answer 16

Treatment of LTBI reduces the risk of developing active TB later in life by about 90%.

Isoniazid (INH) 300 mg PO daily x 9 months

• add vitamin B6 (pyridoxine) 50 mg PO daily
• Hepatotoxicity: check LFT if symptomatic.

ALTERNATIVE regimen:

Rifampin 600 mg PO daily x 4 months
OR
Isoniazide 900 mg + Rifapentine 900 mg PO WEEKLY x 12 months (3 months).

Question 17

Counseling Points

Answer 17

1) Hepatotoxicity - isoniazid, rifamycin (rifamin, rifabutin), or pyrazinamide; patients should report nausea, or abdominal pain and limit alcohol and acetaminophen.
2) Rifamycin cause orange discoloration of urine, sweat, and tears and can permanently stain soft contact lenses.
3) With rifamycins, patient’s complaint of “small red-purple spots” may be a sign of thrombocytopenia; refer to MD.
4) Drug interactions: Rifamycins are INDUCERS and can decrease the following:
-levothyroxine
-phenytoin
-warfarin
-oral contraceptives (patch, ring, or implant).
Suggest switching to depot medroxyprogesterone or an IUD or adding condoms.

5) Advise adding vit B6 to isoniazid
6) Recommend an antihistamine for mild, itchy rash. TB meds can cause itching.

Question 18

Combination Drugs for TB

Answer 18

Rifamate (isoniazid + rifampin) - EMPTY stomach

Rifater (isoniazid + rifampin +pyrazinamide) - EMPTY stomach

Question 19

Pyrazinamide

Answer 19

Hepatotoxicity
Hyperuricemia
Avoid in renal dysfunction

DOSE: 15-30 mg/kg - 2000 mg PO daily

Question 20

What is LTBI?

Answer 20

Latent TB infection - “dormant,” asymptomatic type of infection; infected, but not sick; NOT contagious.

LTBI patient will be PPD+, CXR negative.

LTBI can become active infection as a result of immunosuppression (e.g., steroids, DMARDs, HIV, old age)

Only patients with ACTIVE disease are contagious.

Question 21

Who needs the TB skin test?

Answer 21

1) Close contacts
2) Healthcare workers
3) People who have symptoms of TB (e.g., chronic cough, fever, weight loss, night sweats, fatigue, hemoptysis/ coughing up blood).
4) Job requirement
5) Low immunity conditions (e.g., HIV infection or for patients planning to start DMARDs)

Question 22

Resistant TB

Answer 22

Bedaquiline (Sirturo)

Question 23

Tests used to diagnose TB

Answer 23

1) TB Skin Test (TST) (PPD): given INTRA-DERMAL.
Read test 48-72 hours after administration. It
becomes positive 2-8 weeks after infection with TB
(latent or active infection).

2) CXR: Assists with locating infected areas of the lungs in active TB, or to rule out active TB if PPD+.
3) TB Blood Tests: QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT TB test.
4) AFB: If active TB is suspected, sputum sample can be checked for active TB under a microscope; stained with an acid (AFB: Acid Fast Bacilli) and then sent for culture (which can take weeks).

(+) AFB means active TB

Question 24

Bedaquiline (Sirturo)

Answer 24

Indication: Part of combination therapy for patients 18 years or older with multi-drug resistant-TB (MDR-TB). Should be administered by directly observed therapy (DOT)

DOSAGE FORMS: 100 mg tablets

DOSE: only used in combination with at least 3 other drugs

• Weeks 1-2: 400 mg (4 tabs of 100 mg) PO daily with FOOD
• Week 3-24: 200 mg (2 tabs of 100 mg) 3x per week with food (600 mg per week).

CAUTION: QT prolongation, hepatotoxicity (alcohol & other hepatotoxic drugs should be avoided).

DRUG INTERACTIONs: CYP 3A4 Inducers/inhibitors