DUHS CME - Ojha Institute of Chest Diseases

Tuberculosis

 

 

MODULE 5


Treatment of Tuberculosis

Objectives

After going through this module we will understand

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Treatment of tuberculosis

Treating TB disease benefits both the person who has TB and the community. It helps the patient because it prevents disability and death and restores health; it benefits the community because it prevents the further transmission of TB.

Principles of Chemotherapy
Basis of Treatment
The basis of treatment of tuberculosis is chemotherapy. It is also one of the most efficient means of preventing the spread of tuberculosis microorganisms.


The requirements for adequate chemotherapy are;
  • An appropriate combination of anti-tuberculosis medications to prevent the development of resistance to those medications;
  •  A correct Weight Based dosage;
  • Regular administration and swallowing of each dose under DOT.  Directly observed therapy (DOT) may be ensured by a daily visit to the health facility by the patient or through a treatment supporter ( a respected member of the community e.g. Imam, school teacher, community leader) who would visit the patient at his house daily for administering the drugs.
  • In educating the patients and their relatives on the importance of regular drug intake, DOT and treatment completion must be emphasized.
  • A Full course of treatment regimen to prevent relapse of the disease after the completion of treatment.

Duration of Chemotherapy
Treatment of TB is the cornerstone of any TB programme.  The modern strategy of TB treatment is based on standardized short-course chemotherapy regimens of six months duration. Short-course anti-TB therapy is close to 100% effective when the patient takes every dose of the recommended treatment regimen. In special circumstances like TB Meningitis longer duration for up to 9 months treatment regimens are recommended. Although unpredictable at the start of anti-TB treatment, some patients do not adhere to treatment when it is self-administered. Therefore, one certain strategy to ensure patient adherence to treatment regimens is Directly Observed Treatment (DOT).


Chemotherapy should Not be stopped or interrupted unless severe drug intolerance or toxicity occurs necessitating a special management by a specialist to ensure a proper completion of ATT treatment. 

When the drug susceptibility results are available, clinicians may change the regimen accordingly

ESSENTIAL ANTI-TB DRUGS
There are two main activities of anti-TB drugs:

  •  Early bactericidal activity – the ability of a drug to decrease the number of tubercle bacilli in sputum during the initial period of therapy in actively multiplying subpopulations (= fast decrease of bacterial load)
  •  Sterilizing activity – the ability to eliminate or substantially decrease the number of bacilli in (semi) dormant subpopulations (= ultimate elimination of all bacilli)

CLINICAL INFORMATION ABOUT ESSENTIAL ANTI-TB DRUGS

Rifampicin

Mechanism

A bactericidal drug active against ALL populations of TB bacilli Semi-synthetic, macrocyclic antibiotic inhibiting nucleic acid  Synthesis Potent bactericidal action and potent sterilizing effect against tubercle bacilli

Preparations

150 mg ,300,450 and 600 mg capsule
100mg/5ml syrup

Administration Remarks

  1. Must always be administered in combination with other anti-mycobacterial agents

 

Dosage

  1. 10 mg/kg (8–12 mg/kg) daily
  2. Maximum 600 mg daily

 

Adverse Reaction

  1. Gastrointestinal intolerance
  2. Hepatitis

 

Contraindication

  1. Hepatic dysfunction
  2. Known hypersensitivity to Rifamycins

 

 

Isoniazid

Isoniazid (H) A bactericidal drug active against ALL populations of TB bacilli

  1. Highly bactericidal against replicating tubercle bacilli

Kills 90% during first few days of treatment

Preparations

  1. 50 mg, 100 mg, 300 mg tablets
  2. 50 mg in 2 ml injection(not available in Pakistan )
  3. 50mg/5ml syrup

 

Administration Remarks

  1. Taken orally
  2. Injections reserved for critically ill patients

 

Dosage

  1. 5 mg/kg (4–6 mg/kg) daily
  2. Maximal dose is 300 mg when given daily

 

Adverse Reaction

  1. Hepatic dysfunction
  2. Skin rashes
  3. Neurotoxicity

 

Contraindication

  1. Hepatic dysfunction
  2. Known hypersensitivity

 

 

Pyrazinamide

Pyrazinamide  (Z) A bactericidal drug active against certain populations of TB
bacilli

  1. Particularly active in acid intra-cellular environment and in

areas of acute inflammation

  1. Active in acid environment against bacilli inside macrophages

Synthetic analogue of nicotinamide with weak bactericidal, but potent sterilizing activity against M. tuberculosis

Preparations

400 &500 mg tablet
250mg/5ml syrup

Administration

  1. Highly effective during the first 2 months of therapy

 

Dosage

  1. 25 mg/kg (20–30 mg/kg) daily

Adverse Reaction

  1. Hepatitis
  2. Hyperuricaemia
  3. Rash

 

Contraindication

  1. Hepatic dysfunction
  2. Known hypersensitivity

 

Streptomycin

Streptomycin (S) A bactericidal drug active against certain populations of TB bacilli
Active against rapidly multiplying extra-cellular TB bacilli

Preparations

  1. 1.0 g ampoule injections

Administration Remarks

  1. Streptomycin is an aminoglicoside antibiotic with

bactericidal activity against TB bacilli

Dosage

  1. 15 mg/kg (12–18 mg/kg) daily
  2. In patients over age 60, 500-750 mg daily

 

Adverse Reaction

  1. Vestibular damage
  2. Hypersensitivity
  3. Nephrotoxicity

 

Contraindication

  1. Pre-existing auditory nerve impairment
  2. Renal impairment
  3. Myasthenia gravis
  4. Pregnancy
  5. Known hypersensitivity

 

 

Ethambutol

Ethambutol (E) A synthetic, bacteriostatic drug active against M. tuberculosis and other mycobacteria
Used in combination with other more powerful drugs to prevent emergence of resistant bacilli

Preparations

  1. 100 mg, 250 mg, 400 mg tablets

 

Administration

  1. Used in combination with other anti-TB drugs to prevent the emergence of resistant strains

 

Dosage

  1. 15 mg/kg (15-20 mg/kg) daily

Adverse Reaction

  1. Ocular toxicity

Contraindication

  1. Pre-existing optic neuritis from any cause
  2. Renal impairment
  3. Inability (young children, Unconscious patients) to report visual disturbances
  4. Known hypersensitivity

 

 

Treatment
Tuberculosis treatment should  be started after a firm diagnosis has been made. TB patients should receive a full course of treatment according to their weight, specific regimens and specified duration

No ATT drugs should be given on a trial basis

TB patients can be categorized into 2 major groups:

  • New Cases 
  • Re-Treatment Cases

1. New Cases 
Patients who have never received treatment for tuberculosis or taken it for less than one month. This group includes the following:

  • Smear positive pulmonary tuberculosis.
  • Smear negative pulmonary tuberculosis.
  • Extra-pulmonary tuberculosis.

The treatment for this group of patients should be 6 months short course chemotherapy (SCC).

Initial Intensive Phase:
2HRZE, i.e. Isoniazid, Rifampicin, Pyrazinamide and Ethambutol administered under direct observation daily for 2 months.

Continuation Phase:
4HR i.e. Isoniazid and Rifampacin. daily for 4 months.
Thus this regimen is 2HRZE/4HR on daily basis (DOTS)

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Monitoring during Treatment
Monitoring Timeline for CAT I patients

Perform Sputum smear Examination

Month

1st

2nd

3rd

4th

5th

6th

Beginning of

 

 

 

 

X

 

End of

 

X

 

 

 

X

If

Next Step

At the end of the 2nd month patient is sputum smear-negative (true for vast majority)

Continue with the treatment as planned until the end of regimen

At the end of the 2nd month patient
is sputum smear-positive

  • Prolong the initial phase of regimen for a 3rd month
  • do sputum examination at the end of 3rd month
  •  If at the end of the 3rd month sputum smear negative, start continuation phase
  • If at the end of the 3rd month sputum smear positive,
  •  start continuation phase,
  •  perform culture and susceptibility tests and adjust as needed

If

Next Step

At the start of the 5th month patient
is sputum smear-negative

Continue with the treatment as planned
until the end of regimen

At the start of the 5th month patient
is sputum smear-positive

  • Consider case treatment failure
  • Do drug susceptibility test
  • Re-register patient as treatment failure
  • Start retreatment regimen as treatment failure
  •  Obtain result of sensitivity test
  •  Adapt treatment to susceptibility of bacilli and continue with the treatment

At the end of the 6th month patient
is sputum smear-negative

Patient is considered cured

At the end of the 6th month patient
is sputum smear-positive

Follow the same steps as at the start of 5th month if sputum smear –positive

 

  1. Re-Treatment Cases:

All smear-positive cases identified as “failures”, “treatment after default” and “relapses” should be classified as “retreatment” cases. These patients should  be put on treatment Regimen. Drug susceptibility test should be performed. When results are  known, the regimen may need to be adapted according to the susceptibility test results. New patients smear positive after five months of therapy need to be started on Re-treatment regimen. The recommended treatment for this group of patients is 8 months as follows:

Initial Intensive Phase:
2HREZ+S,
i.e. Rifampicin, Isoniazid, Pyrazinamide, Ethambutol and Streptomycin for 2 months followed by one month of same therapy without streptomycin i.e 1HRZE.

Continuation Phase:
Three drug combination for a period of five months with INH plus Rifampacin and Ethambutal 5HRE.

 

Monitoring Timeline for CAT II patients

Perform Sputum smear Examination

Month

1st

2nd

3rd

4th

5th

6th

7th

8th

End of

 

 

X

 

X

 

 

X

If

Next Step

At the end of the 3rd month patient is sputum smear-negative

  • Start continuation phase

At the end of the 3rd month patient is sputum smear-positive

  • If susceptibility test is not available:
  • Extend initial phase of treatment with 4 drugs by one additional month
  • Start continuation phase after extended initial phase
  • If susceptibility test is available Treat according to susceptibility of bacilli
  • Sensitivity test results show sensitivity to rifampicin and isoniazid, then: continue patient on Re-treatment regimen
  • Sensitivity test results show resistance to 2 or 3 drugs employed in continuation phase, then: refer patient to a centre specialized in treatment with  second-line anti-TB drugs for DR TB treatment

If

Next Step

At the end of 5th month patient is sputum smear negative

  • Continue continuation phase

At the end of 5th month patient is sputum smear positive

  • Obtain a specimen for culture and DST and continue patient in same regimen.

At the end of the 8th month
patient is sputum culture-positive
(smear-negative)

  • Review the result of culture and DST done at the end of 5th month.
  • The patient might be drug resistant. Refer to a national specialist centre for DR TB treatment/ Empiric MDR TB treatment regimen

At the end of the 8th month patient is sputum smear and culture - negative

Patient is considered cured

 

Remember:
Never add a single drug if the patient is not responding well to treatment.

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Adherence to Treatment
Treatment for TB disease lasts longer and requires more drugs than treatment for other infectious diseases. In order to cure TB and prevent drug resistance, patients with TB must follow the recommended course of treatment. This is called adhering to treatment. However, ensuring that patients adhere to treatment can be difficult because many patients are reluctant to take several different medications for many months.

There are many ways to encourage patients to adhere to treatment. The most effective strategy is directly observed therapy (DOT). DOT means that a health care worker or another designated person watches the TB patient swallow each dose of the prescribed drugs. This method of treatment should be considered for all patients because there is no way to predict reliably which patients will adhere to treatment. DOT should be done at a time and a place that are convenient for the patient. For example, health care workers can meet TB patients at work, at home, or in other locations to provide DOT.
DOT should be used for all children and adolescents. Even when drugs are given under DOT, tolerance of the medication must be monitored closely.

Monitoring Patients’ Adherence to Therapy
Patients who are not receiving directly observed therapy (self-administered therapy) should be monitored carefully for adherence to treatment. This can be done in at least four ways:

  • Check to see whether the patient is reporting to the clinic as scheduled, and ask the patient about adherence.
  • Ask the patient to bring the prescribed medications to each clinic visit and count the number of pills to determine how many have been taken.
  • Use special urine tests to detect the presence of the prescribed medication in the urine (not done in Pakistan ).
  • Assess the patient’s clinical response to treatment.

Follow-up
Subsequent relapse is rare when patients complete the prescribed course of chemotherapy. They should be told to report for re-examination if symptoms recur.

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Treatment of Latent TB Infection (LTBI)

LTBI is treated to prevent people who have TB infection from developing TB disease. LTBI is treated with medication.
Specially patients with high risk of TB

  1. People who are at higher risk for becoming infected with M. tuberculosis
  2. People who are higher risk for developing TB disease once infected with M. tuberculosis

People in these groups should be identified through
a positive tuberculin skin test (TST)
or
a QuantiFERON-TB Gold

 

High priority People if they have

  • a positive QFT-G result or
  • a TST reaction* that is 5 or more millimeters

Recent close contacts of people with
infectious TB disease**
People living with HIV**
People with chest x-ray findings suggestive of previous TB disease Patients with organ transplants Other immunosuppressed patients (such as patients on prolonged therapy with corticosteroids, equivalent to taking 15 mg or more of prednisone, or those taking TNF-
alpha antagonists)**

High priority People if they have

  • a positive QFT-G result or
  • a TST reaction* that is 10 or more millimeters

People from areas of the world where TB is common
People who inject illegal drugs. People who live or work in high-risk facilities (for example, nursing homes, correctional facilities, homeless shelters, hospitals, or other health care facilities) People who work in mycobacteriology
laboratories
People with medical conditions that appear to increase the risk for TB disease (silicosis, diabetes mellitus, severe kidney disease, certain types of cancer, and certain intestinal conditions)
Children younger than 5 years Infants, children, and adolescents exposed to adults in high-risk groups**

 

It is necessary to make sure that the person does not have active TB disease before starting LTBI treatment. Is started
Regimens for LTBI Treatment
Isoniazid 9 Month Regimen in HIV patients
Isoniazid – 6 Month Regimen in non HIV patients

 

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Study Questions

Q1. what are the basic principle of anti TB chemotherapy?

Q2. what regimen is prescribed to a New and Retreatment cases?

Q3. give name and doses of 1st line anti TB drugs?

Q4. Define New case of tuberculosis which patients are include in this group?

Q5. which patients are included in retreatment group?

Q6. At what month  of treatment follow up sputum smear examination is required in new case and in retreatment case?

Q7. What are the indications of performing drug sensitivity test in a patient receiving anti TB treatment?

Q8. How will you monitor adherence to treatment in a patient receiving anti TB treatment?

Q9. Enlist patient who are likely to develop TB disease when are infected?

Q10. Which drug is used as prophylactic treatment of TB?

Objectives

After going through this module we will understand

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