Tuberculosis

Question 1

The aims of TB treatment are to:

Answer 1

Cure the patient of TB

• Decrease transmission of TB to others
• Prevent the development of acquired drug resistance
• Prevent relapse
• Prevent death from TB or its complications

Question 2

Intensive Phase

Answer 2

RHZE

(150,75, 400,275)

Question 3

30-37 kg TB dose IP

Answer 3

2 tabs

Question 4

38-54 kg TB dose IP

Answer 4

3 tabs

Question 5

55-70 kg TB dose IP

Answer 5

4 tabs

Question 6

>70kg TB dose IP

Answer 6

5 tabs

Question 7

Continuation phase

Answer 7

7 days a week for 4 months

RH (150,75)

OR

RH (300,150)

Question 8

30-37 kg TB dose CP

Answer 8

(150,75)

2 tabs

Question 9

38-54 kg TB dose CP

Answer 9

3 tabs

RH

(150,75)

Question 10

55-70 kg TB dose CP

Answer 10

RH (300,150)

2 tabs

Question 11

>70kg TB dose CP

Answer 11

RH (300,150)

2 Tabs

Question 12

Isoniazid mono resistant TB treatment

Answer 12

RHZE for 6 – 9 months

Question 13

Any Rifampicin resistant TB treatment

Answer 13

MDR-TB regimen for 18 – 24 months

Question 14

The second line drugs include

Answer 14

levofloxacin,

moxifloxacin,

bedaquiline,

delamanid

and linezolid

Question 15

GROUP A second line drugs

Answer 15

fluoroquinolones (levofloxacin and moxifloxacin), bedaquiline and linezolid

Question 16

Group B second line drugs

Answer 16

clofazimine and cycloserine or terizidone

Question 17

GROUP C tb second line treatment

Answer 17

included all other medicines that can be used when a regimen cannot be composed with Group A and B agents.

Question 18

Current Treatment Regimens for RR/MDR-TB in South Africa

Answer 18

 Most patients with RR/MDR-TB are still receiving the old long regimen made up of KM – MFX – ETO – TRD – Z (18-20 months duration)

 Some patients with RR/MDR-TB have started the short (9-11 months) MDR-TB regimen with an injectable agent: (4-6) KM – MFX – ETO – INHhd – CFZ – Z – E / (5) MFX – CFZ – Z – E

 Some patients have received BDQ to substitute the injectable agent in cases of toxicity or intolerance, within a short or long RR/MDR-TB regimen

 Patients with pre-XDR-TB and XDR-TB currently receive long, individualized regimens containing new and repurposed medicines.

Question 19

Rifampicin MOA

Answer 19

Rifampin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death

Question 20

Rifampicin adverse effects

Answer 20

Anorexia, nausea, abdominal pain

Orange/red coloured urine

Skin itching, rash

Jaundice/hepatotoxicity

Thrombocytopenia/purpura

Question 21

Pyrazinamide MOA

Answer 21

pyrazinoic acid and its ester inhibit the synthesis of fatty acids

Question 22

Pyrazinamide adverse effects

Answer 22

Joint pains

Skin itching, rash

Jaundice/hepatotoxicity

Question 23

Isoniazide MOA

Answer 23

Converted to avtive form by KatG. inhibit the formation of mycolic acids of the bacterial cell wall, causing DNA damage and, subsequently, the death of the bacillus

Question 24

Isoniazide adverse effects

Answer 24

Peripheral nneuropathy

Psychosis

Clinical heptitis

Lupus ike syndrome

Haematological alterations and vasculitis

Question 25

Isoniazide drug interactions

Answer 25

Isoniazid is an inhibitor of the cytochrome P450 (CYP450) system families CYP2C9, CYP2C19, and CYP2E1, but its effect on the CYP3A family is minimal. This inhibitory effect of isoniazid can increase the plasma concentrations of certain drugs to toxic levels.(3,36) The plasma concentrations of anticonvulsants, such as phenytoin and carbamazepine, can increase when these drugs are used in combination with isoniazid

Question 26

Ethambutol MOA

Answer 26

Ethambutol interferes with the biosynthesis of arabinogalactan, the principal polysaccharide on the mycobacterial cell wall

Question 27

Ethambutol advers effects

Answer 27

Retrobulbar neuritis GI side effects

Question 28

Ethambutol drug interctions

Answer 28

Concentration decreased by antacids Ethoniamide may increase its toxic effects

Question 29

Rifampicin drug interactions

Answer 29

Potent CYP 45o inducer will dcerease level of rugs metabolised in this pathway Anything that ends in –nib or –vir Rifabutin levels may increase with HIV meds, antifungals, and macrolides because these inhibit the metabolism of rifabutin

Question 30

TB TREATMENT RECHALLENGE AFTER DRUG-INDUCED LIVER INJURY (DILI) intensive phase

Answer 30

Intensive phase, rechallenge as follows: Continue background regimen (moxifloxacin, oral, 400 mg daily; and ethambutol, oral, 800-1200 mg daily; and either amikacin, IV/IM or kanamycin, IV/IM, 15 mg/kg daily). If eGFR \< 60 mL/min or INR is raised, substitute amikacin/kanamycin with ethionamide. Day 1: Rifampicin 10mg/kg/day (max 600 mg daily) Day 3: Check ALT Day 4-6: If ALT \< 100 IU/l, add isoniazid 5mg/kg/day (max 300 mg daily) Day 7: Check ALT Day 8: If ALT \< 100 IU/l, consider pyrazinamide 25 mg/kg/day Note: Consider pyrazinamide rechallenge in cases of severe forms of TB e.g. miliary TB or TB meningitis, resistance or intolerance to rifampicin and isoniazid. Day 10: Check ALT. If ALT \< 100 IU/l and pyrazinamide successfully rechallenged, re-start TB fixed dose combination (RHZE). If pyrazinamide not rechallenged, continue RHE Stop TB background regimen. Monitor ALT weekly for 4 weeks after rechallenge.

Question 31

TB treatment rechallenge after DILI Coninuation phase

Answer 31

Continuation phase, rechallenge as follows: Continue background regimen (moxifloxacin, oral, 400 mg daily; and ethambutol, oral, 800-1200 mg daily; and either amikacin, IV/IM or kanamycin, IV/IM, 15 mg/kg daily). If eGFR \< 60 mL/min or INR is raised, substitute amikacin/kanamycin with ethionamide. Day 1: Rifampicin 10mg/kg/day (max 600 mg daily) Day 3: Check ALT Day 4-6: If ALT \< 100 IU/l, add isoniazid 5mg/kg/day (max 300 mg daily) Day 7: Check ALT Day 8: If ALT \< 100 IU/l, continue rifampicin and isoniazid to complete the continuation phase Stop TB background regimen. Monitor ALT weekly for 4 weeks after rechallenge.

Question 32

Rechallenge of TB drugs should only be attempted once

Answer 32

ALT is \< 100 IU/L and jaundice has resolved1-3. Do not rechallenge TB drugs if drug-induced liver injury (DILI) resulted in acute liver failure (jaundice with encephalopathy and/or coagulopathy

Question 33

Role of national TB control programmes in research

Answer 33

Applied research Development of new tools Evaluation and demo o new tools Basic research

Question 34

TB preventive therapy Adults and children

Answer 34

INH 5mg/kg/day up to 300mg Children is 10mg/kg/day up to 300mg Give with Pyridoxine 25mg For 6 months up to 9 months Effects last for up to 18 months

Question 35

Recommendations for design of MDR-TB treatment regimen

Answer 35

Use any first-line oral agent to which isolate is sensitive. Isoniazid, rifampicin, ethambutol, or pyrazinamide. 2 Use an injectable to which an isolate is sensitive. An aminoglycoside or capreomycin. Injectable agents used for \>6 months after culture conversion since frequently one of only two bactericidal components of treatment regimen. 3 Use a quinolone. If isolate resistant to a lower-generation quinolone, but sensitive to higher-generation quinolones, consider use of the latter. Quinolones have been used in randomised controlled trials. 4 Add as many second-line bacteriostatic second line agents as needed to make up the five-drug regimen. Among the second-line agents, ethionamide and cycloserine are generally used first because of efficacy, side-effect profile, and price, shown through in-vivo and in-vitro evidence, and historical use in tuberculosis. P-aminosalicylic acid frequently used in patients with higher-grade resistance. 5 Other drugs. If regimen does not contain five adequate medications, consider use of additional agents such as amoxicillin or clavulanate and clofazimine, dependent on clinical status, disease burden, degree, and pattern of resistance and other factors.

Question 36

principles for treating of XDR-TB

Answer 36

Extended regimens consisting of multiple second-line and third-line anti-TB drugs, given for prolonged periods are needed. Many studies included Category E drugs, such as AMX/CLV, CFZ, IPM, LZD and clarithromycin, although their respective contributions could not be readily ascertained. Adjunctive surgery is a potentially useful strategy in carefully selected cases. Indeed, XDR-TB patients should be managed solely by TB specialists.