Tuberculosis Treatment Complete DRUGS – ATT (ANTITUBERCULAR TREATMENT)with MDR

Tuberculosis  Complete DRUGS –

Tuberculosis2
Complete RUGS – ATT (ANTITUBERCULAR TREATMENT)  TREATMENT

Case definitions:

  • 1. Tuberculosis suspect : Any person with symp­toms or signs suggestive of tuberculosis like cough more than 2 weeks.
  • 2. Case of tuberculosis: A patient in whom tuber­culosis is confirmed bacteriologically
  • 3. Definite case of tuberculosis : A patient with positive culture for M. tuberculosis complex or patient with 2 sputum smears showing AFB
Complete RUGS – ATT (ANTITUBERCULAR TREATMENT)  TREATMENT

History of treatment – Definitions for diagnosis:

  • 1. New -A patient who has never taken antituber­cular treatment or taken for less than a month.
  • 2. Relapse -A patient treated for TB and declared cured, or full treatment taken but smear or cul­ture for tuberculosis is positive.
  • 3. Treatment after failure – A patient given An again, after failed previous treatment
  • 4. Treatment after default – If a patient, bacterio­logically positive, interrupts treatment for 2 moths or more and starts An again.
  • 5. Transfer in – A patient transferred from another TB centre for continuation of treatment.
  • 6. Other – Any other case like chronic case, spu­tum positive at the end of repeat treatment.
  • Sometimes pulmonary and extra pulmonary relapse cases may be smear-negative.

ATT Abbreviations Tuberculosis :

  • H, isoniazid; R, rifampin; Z, pyrazinamide; E, ethambutol; S, streptomycin; Q, a quinolone antibiotic; PAS, para-aminosalicylic acid.
  • aAll drugs can be given daily or intermittently (three times weekly throughout or twice weekly after 2–8 weeks of daily therapy during the initial phase).
  • bStreptomycin can be used in place of ethambutol but is no longer considered to be a first-line drug by ATS/IDSA/CDC.

Recommended Antituberculosis Treatment Regimens

  Initial Phase Continuation Phase
Indication Duration, Months Drugs Duration, Months Drugs
New smear- or culture-positive cases 2 HRZEa,b 4 HRa,c,d
New culture-negative cases 2 HRZEa 2 HRa
Pregnancy 2 HREe 7 HR
Failure and relapsef
Resistance (or intolerance) to H Throughout (6) RZEg
Resistance to H + R Throughout (12–18) ZEQ + S (or another injectable agenth)
Resistance to all first-line drugs Throughout (24) 1 injectable agenth + 3 of these 4: ethionamide, cycloserine, Q, PAS
Standardized re-treatment (susceptibility testing unavailable) 3 HRZESi 5 HRE
Drug intolerance to R Throughout (12)j HZE
Drug intolerance to Z 2 HRE 7 HR

 

  • cThe continuation phase should be extended to 7 months for patients with cavitary pulmonary tuberculosis who remain sputum culture–positive after the initial phase of treatment.
  • dHIV-negative patients with noncavitary pulmonary tuberculosis who have negative sputum AFB smears after the initial phase of treatment can be given once-weekly rifapentine/isoniazid in the continuation phase.
Complete RUGS – ATT (ANTITUBERCULAR TREATMENT)  TREATMENT

RUGS – ATT (ANTITUBERCULAR TREATMENT) There are 3 main properties of antituberculous drugs:

  • 1. Bactericidal action
  • 2 Sterilizing activity
  • 3-To prevent resistance.

The first line agents consist of Isoniazid, Rifampin, Pyrazinamide, Ethambutol.

  • These drugs are given orally, once a day.
  • Peak level is at 4 hours and effect lasts for 24 hours. Second line drugs have lower efficacy and more toxicity. These are streptomycin, kanamycin, amikacin, capreomycin, ethionamide, cycloserine, and PAS(Paraamino salicylic acid).
  • Other drugs are Ofloxacin, Levofloxacin, Gatifloxacin, Moxifloxacin, Clofazimine, thiacetazone, amoxycillin and linezolid.
  • Isoniazid and Rifampicin are strong bactericidal drugs. Pyrazinamide and streptomycin are also bactericidal Streptomycin is bactericidal against rapidly multiply­ing tubercle bacilli.
  • Rifampicin is the most potent sterilizing drug. Ethambutol and thiocetazone prevent resistance to drugs.

Standard Treatment Regimens: Treatment is started with:

  • 1 st–  intensive phase for 2 months and
  • 2 nd– continuation phase for 4 – 6 months.

Intensive phase consists of Isoniazid, Rifampicin, Pyrazinamide, and EthambutoL.

This intensive phase results in rapid killing of tubercle bacilli.

  • In two weeks the infectious patient becomes non­infectious, symptoms subside.
  • If patient is smear positive he becomes smear nega­tive in two months.

Continuation phase consists of lesser drugs for longer time.

  • This makes the patient disease-free and prevents re­sistance and relapse.
  • Patients with large bacillary load (which means smear­positive or HIV-infected patients),’ are given short course chemotherapy with four drugs during initial phase and two drugs during continuation.
  • Patients negative for HIV and smear negative tuber­culosis are given rifampicin, isonex, pyrazinamide and ethambutol.
  • Ethambutol may not be given in young children and primary tuberculosis.

Retreatment Regimen:

  • For patients with smear or culture positive tuberculo­sis, 5 drugs in initial phase and 3 drugs in continua­tion phase should be given.
  • Rifampicin, Isonex, Ethambutol are given throughout the treatment.

Standard code for Anti- TB regimens  :

  • Each antitubercular drug has an abbreviation as fol­lows:
  • Rifampicin – R
  • Isoniazid – H
  • Pyrazinamide – Z
  • Streptomycin – S
  • Ethambutol – E
  • Thioacetazone – T.

Any regimen consists of :

  1. Initial phase
  2. Continuation phase
  • The number before a phase is duration of that phase in months.
  • Letters in brackets indicate the names of drugs.
  • A subscript after the letters in brackets indicates num­ber of doses per week. Eg. 2 (HRZE) / 4 (HR)3
  • This means that initial phase of 2 months consists of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol. The

TB Diagnostic TB Patients Category

  • New smear positive patients; New smear negative PTB with extensive parenchymal involvement;
  • Severe concomitant HIV disease or severe forms of EPTB
  • Previously treated sputum smear-positive PTB :
  • – relapse;

treatment after interruption; treatment failure

  • New smear negative PTB (other than in Category I); Less severe forms of EPTB
  • Chronic and MDR – TB cases (still sputum positive after supervised re-treatment)

Treatment Regimen in Special Conditions  Pregnancy:

 

  • Streptomycin is unsafe. It is hepatotoxic to fetus and so should not be used in pregnancy.

Breastfeeding :

  • All drugs are safe. Baby can be given Isoniazid during infectious stage of mother and for 3 months after that.

Oral contraception:

  • Rifampicin interacts with oral contraceptives and de­creases their efficacy.

Liver disease:

  • Isoniazid, Rifampicin and Pyrazinamide can cause hepatitis.
  • Rifampicin is least toxic, but can cause cholestatic jaundice.
  • Pyrazinamide is most hepatotoxic.
  • Patients with chronic liver disease should not take Pyrazinamide.
  • In chronic liver disease patient can take isoniazid and rifampicin with streptomycin and etham­butol for 8 months.
  • In acute he(?atitis, treatment should be delayed till hepatitis resolves otherwise streptomycin and etham-
  • continuation phase is of 4 months consisting of Iso­niazid and Rifampicin given 3 times / week.

TB treatment regimens

  1. Initial phase (Daily Continuation phase
  2. or 3 times weekly) (Daily or 3 times weekly)a
  • Specially designed standardized or individualized regimens are suggested for this category
  • ethambutol can be given for 3 months and when hepatitis is resolved, isoniazid and rifampicin may be given.
  • If acute hepatitis does not resolve for many months then only Streptomycin and Ethambutol should be continued for 12 months.

Renal Failure:

  • In renal failure, Isoniazid, Rifampicin and Pyrazina­mide can be given in normal doses.
  • Pyridoxin should be given with Isoniazid to prevent peripheral neuropathy if renal failure patients.
  • Streptomycin and Ethambutol are avoided or given in low doses.
  • Thiocetazone should not be used.
  • Patients with renal failure should be on 2 HRZ / 4 HR.

HIV infected patients:

  • Thiocetazone is not given. Rest of the drugs can be given.

Chronic and MDR (Mutli-Drug Resistant) TB :

  • Chronic tuberculosis is a patient with tuberculosis who. is sputum-positive after standard treatment with es­sential drugs given for complete duration.
  • MDR TB is a patient who is Multi-Drug Resistant, i.e. who has active tuberculosis with bacilli resistant to at least Rifampicin and Isoniazid.

Minor

  • Anorexia, nausea, abdominal pain Joint pains.
  • Burning sensation in the feet
  • Orange j red urine
  • Pyrazinamide Isoniazid

Major

  • Itching, skin rash Deafness (no wax on auroscopy) Dizziness (vertigo and nystagmus) Jaundice (other causes excluded) hepatitis
  • Confusion (suspect drug induced acute liver failure if jaundice present)
  • Visual impairment (other causes excluded)
  • Shock, purpura, acute renal failure
  • Thioacetazone (SHRZ) Streptomycin
  • Isoniazid, Pyrazinamide, rifampicin
  • Reserved drugs for tuberculosis are Amikacin, Kapriomycin, Ciprofloxacin, Cycloserine, Ethionamide, Kanamycin, Ofloxacin, p-aminosalycilic acid.

Management

  • Continue anti-TB drugs, check drug doses Give drugs with small meals or last thing at night
  • Aspirin
  • Pyridoxine 100 mg daily
  • Reassurance, Patients should be told when starting treatment that this commonly happens and is normal.

Stop responsible drug(s) Stop anti-TB drugs

  • Stop streptomycin use ethambutol
  • Stop anti-TB drugs
  • Urgent liver function tests and prothrombin time

Management of Drug Induced Hepatitis:

  • Isoniazid, Pyrazinamide, Rifampicin, and rarely Etham­butol can damage the liver.
  • When a patient develops hepatitis during tubercular treatment, all An should be stopped till liver func­tion tests become normal, or An is not given for 2 weeks after jaundice has disappeared. Rifampicin can give rise to jaundice without hepatitis and symptoms.
  • For patients with drug-induced hepatitis Streptomy­cin, and Ethambutol may be given.

Anti Tuburculous Drug Isoniazid

  • • Highly bactericidal
  • · Given orally (1M also available)
  • · Dose 5 mgjkg or 300 mgjday
  • · Preventive dose 300 mgjday for 6 months
  • · Contraindications – Active liver disease,

Hypersensitivity.

  • In malnutrition, alcoholics, and diabetics, patient should be given pyridoxine 10 mgjday with Isoniazid.

Adverse Effects :

  • Peripheral neu ropathy Optic neuritis
  • Toxic psychosis Generalized convulsions Hepatitis.

Side effects :

  • Nausea
  • Vomiting Dizziness
  • Blurred vision Slurring of speech Seizures.

Rifampicin —

  • Strong bactericidal drug
  • Should be given 30 minutes before meals Dose is 10 m k or 150 – 600 mg daily
  • The drug causes red coloration of urine, tears, saliva, sweat, sputum and contact lenses. Contraindications:
  • Hypersensitivity Liver dysfunction.

Adverse effects :

  • Gastro-intestinal disturbances Fever
  • Flu-like syndrome Thrombocytopenia Skin rashes Exfoliative dermatitis Oliguria
  • Dyspnoea
  • Hemolytic anaemia
  • Hepatitis (which may be fatal).

Pyrazinamide

  • Weak bactericidal, potent sterilizing activity. Dose – 30 mgLkgLQay.

Contraindications :

  • Hypersensitivity Hepatic impairment.

Adverse effects :

  • Gastrointestinal disturbances Increased serum transaminases Hyperuricemia
  • Gout
  • Arthralgia.

Streptomycin It is bactericidal.

  • Given by deep intramuscular injection.
  • Dose – 15 mg/kg/day or 750 mg – 1 gm /day. Contraindications :
  • Hypersensitivity Auditory nerve deafness Myasthenia gravis
  • Should not be used in pregnancy as it causes deafness and nephrotoxicity in the fetus.

 

Adverse effects :

 

  • Injection abscess Hypersensitivity
  • Impairment of vestibular function – Headache, vomiting, vertigo and tinnitus
  • Nephrotoxicity
  • Hemolytic anaemia
  • Aplastic anaemia
  • Agranulocytosis
  • Thrombocytopenia
  • Streptomycin should not be given to patients who are to receive neuromuscular blocking agents during anaesthesia.

 

Ethambutol —

  • Its role is to prevent emergence of resistant strains. Dose – 15 mgLl<g/daL

Contraindication:

 

  • . Hypersensitivity
  • .• Optic neuritis
  • Creatinine clearance < 50 ml/min.

 

Adverse effects :

 

  • Optic neuritis – Visual impairment and loss of colour vision
  • Blindness
  • Peripheral neuritis