When the bacteria that causes tuberculosis (TB), Mycobacterium tuberculosis, develops resistance to the antimicrobial drugs used to cure the disease, this condition is known as Drug-resistant Tuberculosis. 

Premature interruption in the treatment of TB is the leading cause of drug resistance. This poses a great risk to the healthy population, including the patient's family. The reason: the family think that the person is cured after taking the prescribed course of medicines. They stop taking precautions around the patient and sometimes, even stop taking the patient for follow-up routine tests to detect the presence of the disease. This increases the chances of transmission to the family members and their friends, too.

  1. Drug-resistant TB in India
  2. Types of Drug-resistant TB
  3. Diagnosis of Drug-resistant TB
  4. Pre-treatment evaluation for Multidrug-resistant TB and Extensively Drug-resistant TB
  5. Treatment regimen for Multidrug-Resistant TB
  6. Treatment regimen for Extensively Drug-Resistant TB
  7. Prevention of Drug-resistant TB
  8. Treatment protocol for previously treated tuberculosis
  9. Tuberculosis: fact sheet

According to the Indian Council of Medical Research (ICMR), drug-resistant TB has existed in India for more than 40 years.

In 2016, around 490,000 people developed Multidrug-Resistant TB (MDR-TB) worldwide, and about 110,000 people were diagnosed with rifampicin-resistant TB (RR-TB). The countries with the largest numbers of MDR-TB and RR-TB cases (47%) were China, India and the Russian Federation. (Rifampicin is often the first medicine that doctors prescribe for TB patients.) 

India accounted for around 65,000 cases of drug-resistant TB in 2017, according to the World Health Organization (WHO). India has been listed amongst the top 30 countries with most cases of MDR-TB and extensively drug-resistant tuberculosis (XDR-TB).

Depending on how many drugs are ineffective in treating the patient, drug-resistant tuberculosis is divided into:

  • Multidrug-Resistant TB (MDR TB): TB that does not respond to isoniazid and rifampicin, the two most powerful anti-TB drugs.
  • Extensively Drug-resistant TB (XDR TB): A rare type of MDR TB. Along with its resistance to isoniazid and rifampin, it doesn't react to any fluoroquinolone. This type of TB is also resistant to one of three injectable second-line drugs, i.e., amikacin, kanamycin, or capreomycin.
  • In India, tests like line probe assays and Gene Xpert machines are used to determine the presence of M. Tuberculosis in the sputum.
  • Revised National Tuberculosis Control Programme (RNTCP) certified laboratories perform susceptibility testing in cases of drug-resistant TB.
  • Microscopic-observation drug-susceptibility assay (MODS) is a rapid test based on the observation of cord formation of M. tuberculosis that is seen microscopically in liquid medium with the use of an inverted microscope. In MODS, simple light microscopy is used to detect early growth of M. tuberculosis as "strings and tangles" of bacterial cells.
  • TK Medium is another test which can help in the identification of bacteria in the sputum. It is a colorimetric system that indicates the growth of TB bacteria by changing the colour of the growth present in the medium.
  • Mycobacteria Growth Indicator Tube system, introduced by Becton Dickinson, a medical technology company in the US, is used for the rapid detection of resistance to first- and second-line anti-TB drugs.
  • The total duration of treatment for Multidrug-resistant TB (MDR-TB) is 24–27 months.
  • The treatment is given in two phases, the intensive phase and the continuation phase. 
  • The intensive phase regimen comprises six drugs: kanamycin, levofloxacin, ethionamide, pyrazinamide, ethambutol and cycloserine, which are given for six to nine months.
  • The continuation phase regimen comprises four drugs: levofloxacin, ethionamide, ethambutol and cycloserine, which are given for the next 18 months.
  • All drugs should be given in a single daily dosage under supervision. 
  • Pyridoxine (vitamin B6) should be administered to all patients on the regimen for MDR-TB.
  • Along with pre-treatment evaluation, patients should consult with a thoracic surgeon to discuss surgery options in the case of Extensively Drug-Resistant TB (XDR-TB).
  • The intensive phase of treatment for XDR-TB consists of seven drugs: capreomycin (Cm), P-AminoSalicylic acid, moxifloxacin (Mfx), high-dose Isoniazid, clofazimine, linezolid and amoxiclav, which are given for a period of six to 12 months. 
  • Mid-treatment sputum culture test is done to check if the intensive phase of treatment needs to be extended: if the sputum test comes back positive, the intensive phase extends to the next 3 months and so on.
  • The continuation phase for extensive resistance to TB medicines consists of six drugs: P-AminoSalicylic acid, moxifloxacin (Mfx), high-dose Isoniazid, clofazimine, linezolid and amoxiclav, which are given for a period of 18 months.
  • Because of the use of drugs with different toxicity profiles, XDR-TB requires more intensive monitoring during follow-up, which includes monthly complete blood count, kidney function test, serum electrolytes, liver function tests during the intensive phase, and every three months during the continuation phase.
  • Chest X-ray has to be done every six months.

World Health Organization data show that there is a huge gap between the estimated number of drug-resistant TB cases in India and the number of people who are enrolling for treatment. This is partly because of the cost and duration of treatment for drug-resistant TB.

Another reason for this is lack of awareness about drug-resistant TB and unwillingness to go for regular testing.

Family members of people who have had TB in the past must take care that the patient gets proper treatment. It is also important that patients talk to their doctors after their prescribed course of medicines is complete - the doctor may prescribe further tests to check if the bacterial infection is completely gone.

TB, including drug-resistant TB, is very contagious. If possible, use face masks in public.

According to the World Health Organization (WHO) Global Tuberculosis Report 2019, 91% of cases of drug-resistant TB in India comprise people who have been treated for TB in the past.

To be sure, not all cases of relapse lead to drug-resistant TB. Here is the special protocol for people who have been previously treated for TB but don't have drug-resistant TB:

  • The intensive phase in case of previously treated tuberculosis comprises two months of taking isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E), along with streptomycin (S).
  • This is followed by one month of isoniazid, rifampicin, pyrazinamide and ethambutol.
  • The patient should get a follow-up sputum examination at the end of three months. 
  • If the sputum smear is positive at the end of three months of treatment, the intensive phase is extended for another month.
  • Irrespective of the sputum results, at the end of the extended intensive phase, doctors begin the continuation phase of treatment. During this phase, patients are prescribed isoniazid, rifampicin and ethambutol thrice a week, on alternate days, for five months.

According to the WHO Global Tuberculosis Report 2019, India accounts for 27% of all tuberculosis (TB) cases in the world. We have an estimated prevalence of three million TB cases, with two million new cases reported each year. About 280,000 people die from TB in India annually.

WHO data show that of the 2.74 million new cases of TB in India in 2017, more than half (1.78 million) were men. 

What is Tuberculosis?

Tuberculosis (TB) is an infection caused by the bacteria Mycobacterium tuberculosis that most often affects the lungs. It is reported with persistent coughing with sputum for more than three weeks.

Symptoms: The symptoms of TB include cough with sputum for more than two weeks, cough with blood at times, chest pains, weakness, weight loss, fever and night sweats.

  • Vaccine: Infants under 12 months of age are usually given 0.05 mL of Bacillus Calmette–Guérin vaccine intradermally, i.e., through the skin, to prevent TB. Adults are given 0.1 mL of vaccine intradermally.
  • How it spreads: Mycobacterium tuberculosis is transmitted through the air, carried in airborne particles called droplet nuclei - these are 1 - 5 microns in size. Infectious droplet nuclei are formed when persons who have TB cough, sneeze, shout or sing. Transmission occurs when a healthy person inhales droplet nuclei containing Mycobacterium tuberculosis.
  • Types of TB: There are at least three types of TB - TB disease, latent TB and drug-resistant TB. TB patients typically have active TB germs and have all the symptoms of tuberculosis. Germs can spread to others via cough. Patients with latent TB infection do not carry any symptoms and they do not spread the disease to others. But if their germs become active, they can develop TB disease.
  • Treatment protocol for first-time tuberculosis: Treatment is done in two phases for a person who has been exposed to TB for the first time:
    • Intensive phase: The patient is given isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) for two months.

    • Continuation phase (CP): Patients are usually given isoniazid and rifampicin for four months.

  • Under the DOTS programme, the drugs are given thrice weekly for both pulmonary and extra-pulmonary tuberculosis patients. If the sputum smear is positive after two months of treatment, the intensive phase of four drugs is continued for another month.

  • Irrespective of the sputum results after this extended period of the intensive treatment, four months of the continuation phase treatment is started.

  • If the sputum smear is positive after five or more months of treatment, the treatment is declared as a “Failure” and the patient is placed on the “Previously Treated” treatment regimen.

  • Non-DOTS Treatment Regimen under Revised National Tuberculosis Control Programme (RNTCP)
    • Non-DOTS treatment is advised in patients with adverse reactions to rifampicin and/or pyrazinamide and new patients who refuse DOTS despite all efforts. This is a treatment regimen of 12-month duration comprising two months of streptomycin, isoniazid, ethambutol (abbreviated as 2 SHE) and 10 months of isoniazid, ethambutol (often simply called 10 HE by medical professionals and pharmacists).

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