TB treatment - TB drugs, failure, duration, relapse

TB treatment usually involves the patient with TB taking a combination of different TB drugs. Now that drugs are available surgery is rarely used as treatment for TB. If the correct drugs are taken for the entire duration of treatment, then they will for most patients provide a cure for TB.

TB treatment,  the drugs

There are more than twenty drugs available for TB treatment. They are used in different combinations in different circumstances.

General principles of drug treatment of pulmonary TB

Some general principles of pulmonary TB drug treatment (sometimes referred to as TB chemotherapy) are:

  • Drug treatment is the only effective treatment for TB;
  • Single drug treatment for active TB is associated with a substantial relapse rate.
  • A patient is said to have a relapse if they improve whilst taking TB treatment but become ill again after they have finished their treatment;
  • Patients with active TB disease should receive at least three drugs as their initial TB drug treatment. Fewer than three drugs can result in the development of resistance;
  • Never add a single TB drug to a failing regimen. A regimen simply means the course of treatment, in this instance the combination of TB drugs;
  • Compliance with TB treatment is the responsibility of the treating physician as well as the patient.

TB drug treatment is sometimes referred to as antitubercular treatment or ATT.

TB bacteria

Archbishop Desmond Tutu was treated for TB as a child

Archbishop Desmond Tutu was treated for TB as a child

TB is caused by bacteria which are in a person's body. The TB drugs have the aim of killing all the TB bacteria in the person's body. This means that the person is then cured of TB.

But TB bacteria die very slowly, and so the drugs have to be taken for several months. Even when a patient starts to feel better they can still have bacteria alive in their body. So the person needs to keep taking the drugs until all the bacteria are dead.

All the drugs must be taken for the entire length of the TB treatment. If only one or two TB drugs are taken then only some of the bacteria may be killed. They may then become resistant to the TB drugs which then don't work. If the person becomes sick again then different TB drugs called second-line drugs may be needed.

FDCs are when several drugs are put together in one tablet or pill. This helps to ensure that all the drugs are taken. There is more about FDCs.

First line drugs for TB treatment

The first line drugs are:

  • Isoniazid
  • Rifampicin
  • Pyyrazinamide
  • & Ethambutol

which are the TB drugs that generally have the greatest activity against TB bacteria. The amount of drug that a TB patient needs to take depends on the patient's weight. There is more about this on the page about TB drugs.

Treatment categories

To decide what treatment patients need, the World Health Organisation (WHO) used to put patients into TB treatment categories. But with the increasing availability of drug susceptibility testing (DST), treatment categories were abolished, and DST is now used instead to decide on the treatment that patients need.

New patients

New patients are those who have not had TB treatment before, or they have received less than one month of anti TB drugs. New patients are presumed to have drug susceptible TB (i.e. TB which is not drug resistant) unless :

  • There is a high level of isoniazid locally in new TB patients, or
  • the patient has developed active TB disease after known contact with a patient who is documented  as having drug resistant TB.

For new patients with presumed drug susceptible pulmonary TB, the World Health Organisation (WHO) recommends that they should have six months of treatment. This consists of a two month intensive phase followed by a four month continuation phase.

For the two month intensive TB treatment phase they should receive:

  • Isoniazid
  • plus rifampicin
  • plus pyrazinamide
  • plus ethambutol

followed by

  • Isoniazid
  • plus rifampicin

for the continuation treatment phase.

It is recommended that patients take the TB drugs every day for six months. Taking the drugs three times a week used to be considered satisfactory but is no longer recommended by the WHO. It is essential that all the recommended TB drugs are taken.

If only one or two drugs are taken, then the TB treatment probably won't work.

Treatment for patients previously treated

If patients have been previously treated it is essential that they have a drug susceptibility test to find out if they have any drug resistance.

If the bacteria that they are infected with are not resistant to any of the first line drugs then the standard first line treatment of 2HRZE/4HR can be repeated. If there is resistance then an MDR-TB regimen should be prescribed according to WHO's guidance for the treatment of drug resistant TB. The drug streptomycin should now only be given as part of a regimen for the treatment of drug resistant TB.

There is more about this on the TB drugs page.

TB treatment failure

It is often suggested that TB treatment fails because a patient doesn’t take their TB drugs correctly. However there can be a number of different reasons for TB treatment failure. It is certainly true that if a patient doesn’t take their TB drugs properly that this can lead to the development of drug resistant TB. However the patient may already have drug resistant TB. If they already have drug resistant TB, then the treatment that someone is provided with may result in treatment failure even if the treatment is taken correctly.

The three main causes of treatment failing, relate to the actions of doctors in prescribing incorrect regimes, the fact that there may be problems with the drugs being delivered (either when they are delivered or the quality), and that patients for a number of reasons may not have a sufficient intake of the drugs.1Based on Lambregts-van Weezenbeck, C. S. “Control of drug-resistant tuberculosis” Tubercle and Lung Disease, (1995) 76, 455

It is not just in high burden countries that there can be problems with the supply of anti tuberculosis drugs. In the UK almost two thirds of hospital pharmacy departments reported problems with accessing anti tuberculosis treatment.2Capstick TG, “Treatment interruptions and inconsistent supply of anti-tuberculosis drugs in the United Kingdom”, Int J Tuberc Lung Dis, 2011;15(6):754-76 https://www.ncbi.nlm.nih.gov/pubmed/21575294

Doctors – as a cause of TB drug treatment failure:

  • Inappropriate guidelines,
  • Non compliance with guidelines,
  • Absence of guidelines.

Drugs – as a cause of inadequate treatment:

  • Poor quality,
  • Irregular supply,
  • Wrong delivery (dose/combination),
  • Drugs are unsuitable due to drug resistance.

Patients – as a cause of TB drug treatment failure:

  • Lack of information,
  • Lack of money for treatment and/or transport,
  • Actual or presumed side effects,
  • Lack of commitment to a long course of drugs,
  • Malabsorption,
  • Social barriers.

Patients who experience only a short improvement whilst on treatment, or who never respond to treatment, are said to have failed their TB treatment. Treatment failure is also sometimes defined as the continued presence of positive sputum or culture (positive result to a culture test).  It can also be that positive sputum or culture appears again during the course of a patient’s anti tuberculosis drug treatment (att).3“Monitoring of relapse, treatment failure and drug resistance”, British HIV Association www.bhiva.org/

After three months of drug treatment for pulmonary TB caused by drug susceptible bacteria, 90-95% of patients will have negative sputum or culture and show clinical improvement. Normally it is considered that if a patient still has a positive culture  after three months of treatment, the patient must be carefully evaluated to identify why their positive culture hasn’t changed to negative. Patients whose sputum culture remains positive after four months of drug treatment should be classified as treatment failures. If drug treatment failure occurs then a sample should be sent to a reference laboratory for drug susceptibility testing for both first and second line drugs.

Relapse & recurrence

A patient is said to relapse if they become and remain culture negative (or they become well) whilst on TB treatment, but become culture positive (or become ill) again after finishing their TB treatment.

Recurrence of active TB is usually used to refer to the situation when a person’s first TB treatment appears to have been successful. There has then been a significant time interval before active TB develops again. This may either be because of reactivation of the person’s previously latent TB or because they have been reinfected. If any of these situations occur it must be considered a real possibility that the person has drug resistant TB. Their new TB treatment programme must be decided taking this into account.

TB treatment monitoring

Patients collecting more drugs for their TB treatment by presenting the empty packages from the last week.©WHO/TBP/Ger Steenbergen

Patients collecting more drugs for their TB treatment by presenting the empty packages from the last week.©WHO/TBP/Ger Steenbergen

All patients receiving TB treatment should be monitored during their treatment to assess their response to the drug treatment. Regular monitoring also helps to ensure that patients complete their treatment. It can also help to identify and manage adverse drug reactions. Patients also need to have their weight checked every month, and if the patient’s weight changes the drug dosages may need to be adjusted.4“Guidelines for treatment of Tuberculosis”, WHO, Geneva, 2010, 85
The patient also needs to have an adequate intake of food. There is more about food & TB.

When patients have pulmonary TB the patients response to TB treatment should be monitored using sputum smear microscopy. The recommendation from WHO is that for smear positive TB patients treated with first line drugs, the patients should have smear microscopy performed at the end of the two month intensive phase of treatment.

Positive sputum smear

If the patient has a positive sputum smear at the end of the intensive phase, then there should be a patient assessment carried out. This is because the positive smear could indicate a number of different situations. An example is that the patient might have drug resistant TB, and a change in the TB drugs they are taking might be needed. Alternatively, patient adherence might have been poor, and they might not have been taking their drugs correctly. So the assessment might result in changes needing to be made to the patient’s treatment, or to their support and supervision. Different action may need to be taken in a variety of other circumstances, such as the patient having received treatment before.

New molecular tests, such as the GeneXpert TB test, cannot be used for TB treatment monitoring as they detect both live and dead bacteria, and cannot distinguish between them.5“Early tuberculosis treatment monitoring by Xpert MTB/RIF”, European Respiratory Journal, May 1 2012 //erj.ersjournals.com/content/39/5/1269.extract#

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