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Treatment of Tuberculosis

Tuberculosis is a chronic infectious disease that is difficult to treat due to its chronic nature, potential for drug resistance, and adverse drug effects. Standard first-line drugs include isoniazid, rifampin, pyrazinamide, and ethambutol, while second-line drugs are used for drug-resistant cases. Treatment involves a multi-drug regimen administered over a period of 6-24 months depending on the type of TB and patient factors. Directly observed therapy is recommended to ensure adherence and prevent drug resistance.

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Malavika A G
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20 views19 pages

Treatment of Tuberculosis

Tuberculosis is a chronic infectious disease that is difficult to treat due to its chronic nature, potential for drug resistance, and adverse drug effects. Standard first-line drugs include isoniazid, rifampin, pyrazinamide, and ethambutol, while second-line drugs are used for drug-resistant cases. Treatment involves a multi-drug regimen administered over a period of 6-24 months depending on the type of TB and patient factors. Directly observed therapy is recommended to ensure adherence and prevent drug resistance.

Uploaded by

Malavika A G
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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TREATMENT OF TUBERCULOSIS

DR.V.KRISHNAN . M .D , C.Diab
• TB- Chronic granulomatous pulmonary or extra pulmonary
disease

• Difficult treatment - Due to chronicity , adverse effects and


resistance emergence .

First line drugs –High efficacy , less side effects


• Isoniazid , rifampicin , pryazinamide , ethambutol , streptomycin
Second line older drugs- Low efficacy , more side effects
• Cycloserine , ethionamide , PAS , Thiacetazone
Second line newer drugs – More efficacy , used in resistant TB cases
• Quinolones –Ciprofloxacin , Moxifloxacin
• Aminoglycosides – Amikacin , Kanamycin
• Macrolides –Azithromycin , Claithromycin
Isoniazid –First line , essential tuberculocidal drug

• Inhibits mycolic acid synthesis of bacilli cell wall

• Acts best on fast and slow multipliers , intra and


extracellular bacilli , in acidic and alkaline medium

• Metabolised by acetylation ( slow and fast acetylators)

• Resistance is due to mutation katG gene

• ADR- Peripheral neuropathy ( treated with pyridoxine


100mg/day ) , hepatitis , seizures at large doses
• Rifampicin – Tuberculocidal drug ,

• Acts best slow dividing , dormant organisms , prevents resistance

• Inhibits DNA dependent RNA synthesis , encoded by rpoB gene

• Resistance is due to mutation in rpoB gene gene

• It is a Potent microsomal enzyme inducer

• ADR –Orange secretions , hepatitis , cutaneous , abdominal or flu like


syndrome , Renal Failure , thrombocytopenia

• Other uses –leprosy , meningococcal infection , MRSA , leigionella and


brucellosis
• Pyrazinamide –
• Tuberculocidal drug ,
• Inhibit mycolic acid synthesis
• More active in acidic medium ,
• Inside tuberculous cavity , has good sterilising
activity .
• Resistance is due to mutation pncA gene
• Good tissue and CSF penetration
• Causes hepatotoxicity , hyperuricemia ,
hyperglycemia , arthralgia
• Ethambutol –
• Tuberculostatic ,
• Inhibit arabinoglactan syntheis and mycolic acid
synthesis of cell wall
• More active on fast dividing bacilli
• Increase sputum conversion
• Resistance is due to mutation embAB gene
• Causes , ethambutol optic neuritis relatively contra
indicated in children below 6 years ,
hyperuricemia , renal failure
• Streptomycin –First drug used for TB

• Tuberculocidal

• Inhibit protein synthesis , binds 30s ribosomes .

• Cannot penetrate barriers ,

• Not active on acidic medium ,

• Has to be given by injection ,

• Resistance and dependence is common

• Causes oto and nephrotoxicity


Second line older drugs –
• Thiacetazone – low wfficacy drug with high skin and
liver toxicity

• PAS – very low efficacy drug , Used as add on drug in


MDR cases

• Ethionamide –low efficacy drug , not used except in


resistant cases

• Cycloserine – inhibits cell wall d-alanine , causes


psychosis and convulsions ( treated with pyridoxine )
Second line Newer drugs –

• Quinolones –Ciprofloxacin , Moxifloxacin


• Aminoglycosides – Amikacin , Kanamycin
• Macrolides –Azithromycin , Claithromycin
Used in
- Resistant TB cases ,
- Adverse effects to conventional drugs
- To prevent atypical mycobacterial infection

• Rifabutin
- Rifampicin congener , inhibit DNA dependent RNA polymerase
- Less enzyme inducer , given along with HIV drugs
- Also active against atypical mycobacteria
• Short course chemotherapy –DOTS
• Treatment depends on , site , sputum positivity and
history of previous treantment under RNTCP
programme
• Rationale of DOTS
• Initial phase –
• Initial treatment with 4 or 3 drugs to kill bacilli rapidly
• Bring sputum conversion –Prevents spread
• Bring improvement in symptoms
• Continuation phase –
• Give 2 or 3 drugs to kill slow , dormant bacilli
• Achieve complete bacilli elimination
• Prevent resistance and relapse
• Treatment  groups 

New (Cat I) 


•        New Sputum smear-positive or negative  
•        New Extra-pulmonary 
•        New Others 

Intensive Phase (IP) = 2 ( Isoniazid 300 mg ,


Rifampicin 600 mg , Ethambutol 1500 , Pyrazinamide
2500mg ) * Thrice weekly * Two months
Continuation Phase (CP) =   ( Isoniazid 300 mg ,
Rifampicin 600 mg ) * Thrice weekly * Four months
• Treatment  groups 

Previously Treated (Cat II) 


•         Relapse 
•         Failure 
•         Default 
•         others 

Intensive Phase (IP)

• ( Isoniazid 300 mg , Rifamicin 600 mg , Ethmabutol 1200 mg , Pyrazinamide


2500 mg , Steptomycin 1 gm im ) * Thrice weekly * Two months
• ( Isoniazid 300 mg , Rifampicin 600 mg , Ethambutol 1200 mg,
Pyrazinamide 2500 , Streptomycin 1 gm im ) * Thrice weekly * One month

• Continuation Phase (CP) -   ( Isoniazid 300 mg , Rifampicin 600 mg ,


Ethambutol 1200 mg , ) * Thrice weekly * Five months
• MDR TB-DOTS PLUS -

• 10 % of TB is MDR , often in HIV co infection

• Resistance to isoniazid and /or rifampicin as well to other drugs

• Difficult treatment
• For 18-24 months with second line drugs ,
• More toxic and expensive
• 5-6 drugs with two first line drug /one quinoloes/one injectable
aminoglycoside / two older drugs should be given

• RNTCP Regimen for MDR TB:


• 6 -9 Month - Kanamycin, Levofloxacin , Ethionamide, Cycloserines, ,
Ethambutol , Pyrazinamide
• 18 - Kanamycin, Levofloxacin , Ethionamide, Cycloserines, , Ethambutol
• XDR TB –Extensive rug resistance

• 2- 3 % of MDR Very high mortality

• More common among HIV patients

• Resistance to four , effective bactericidal drugs –rifampicin


/isoniazid /a quinolone/a aminoglycoside

• The Intensive Phase (6-12 months) will consist of 7 drugs –


Capreomycin (Cm), PAS, Moxifloxacin (Mfx), High dose-INH,
Clofazimine, Linezolid, and Amoxyclav

• The Continuation Phase (18 months) will consist of 6 drugs – PAS,


Moxifloxacin (Mfx), High dose-INH, Clofazimine, Linezolid, and
Amoxyclav .
• TB in pregnancy and breast feeding women

• Treatment Should not be withheld


• Pregnant women – 2 months HRE AND
7months HR
• Breast feeding women – Treatment given with
mother and baby should be monitoring
• Infant given BCG vaccination and isoniazid
prophylaxis for 6 months
• TB prophylaxis ---
• To contacts of open cases with mantoux positive
• Children with positive mantoux and TB patient in
family
• Neonate of TB mother
• High risk immunosuppressive pt
Regimen followed
• Isoniazid -6 months
• Pyrazinamide /ethambutol/quinolones for
suspected MDR cases
• For Infants of TB Mother , BCG vaccination and
isoniazid prophylaxis for 6 months
• Role of steroids in TB treatment

• In very ill patients


• In pts with severe manifestations
• To reduce hypersentivity to TB drugs
• In cases of serosal involvement –pleura or
meningeal TB

• CONTRAINDICATED IN INTESTINAL – TB to avoid


silent perforation
• TB AND HIV –
• Common in HIV patient , MDR TB also common

• Complex treatment with high toxicity , drug


interactions

• -2 HRZE and 7 HR with pyridoxine 25mg

• Rifabutin may be given for rifampicin when pt on


treatment with protease inhibitors , as it less
microsomal enzyme inducer
• MAC treatment

• Ethambutol/rifampicin/claithromycin/ quinolone-
for 6 months
• Claithromycin /ethambutol for 2 months or untill
CD4 rises above 100 cell/microlite

• Prophylaxis with claithro/azithromycin till CD4 rises


above 100 cell/microlite

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