TB Treatment

TB treatment, the aims

The aims of TB treatment are:1

  • To cure the patient and restore quality of life and productivity;
  • to prevent relapse of TB;
  • to reduce the transmission of TB to others;
  • to prevent the development and transmission of drug resistant TB.

TB treatment, the benefits

TB treatment can cure most people who have TB, using a combination of the different drugs available for TB treatment. Surgery is also occasionally used in the treatment of TB.

TB treatment, the drugs

There are more than twenty drugs available for TB treatment, and they are used in differing combinations in different circumstances. So for example, some TB drugs are only used for the treatment of new patients when there is no suggestion of any drug resistance, whereas others are only used for the treatment of drug resistant TB.2 More than 90% of people with drug susceptible TB (that is TB which is not drug resistant) can be cured in six months using a combination of "first line" TB drugs.3

Killing the TB bacteria

The TB drugs that are taken for the treatment of TB, have the aim of killing all the TB bacteria in the person's body. However, TB bacteria die very slowly, and so the drugs have to be taken for quite a few months. Even when a patient starts to feel better they can still have bacteria alive in their body, and so the person needs to keep taking the treatment until all the bacteria are dead.

All the TB drugs must be taken for the entire period of treatment. If only one or two TB drugs are taken then the bacteria may not all be killed and they can become resistant to the drugs which then don't work. If the person becomes sick again then different TB drugs may be needed.

Causes of inadequate TB treatment

Although it is often suggested that inadequate TB treatment occurs because a patient fails to take their TB drugs correctly, there can be a number of reasons for inadequate TB treatment. Inadequate TB treatment can lead to the development of drug resistant TB, but the treatment that someone is provided with, may also be inadequate because they already have drug resistant TB.

In addition to a lack of, or inadequate health infrastructure, the three main causes of inadequate TB treatment relate to the actions of doctors in prescribing inadequate regimes, the fact that there may be problems with the drugs delivered, and that patients for a number of reasons may have an inadequate drug intake.4

Doctors - as a cause of inadequate TB treatment
Inappropriate guidelines
Non compliance with guidelines
Absence of guidelines
Drugs - as a cause of inadequate TB treatment
Poor quality
Irregular supply
Wrong delivery (dose/combination)
Drugs are unsuitable due to drug resistance
Patients - as a cause of inadequate TB treatment
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

General principles of drug treatment of pulmonary TB

Some general principles of pulmonary TB 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 and with the development of bacteria that are resistant to the drug;
  • Patients with active TB disease should receive at least three drugs as their initial TB treatment, as fewer than three drugs can result in the development of resistance;
  • Never add a single drug to a failing regimen;
  • Compliance with TB treatment is the responsibility of the treating physician as well as the patient.

First line drugs for TB treatment

The first line drugs:

  • Isoniazid
  • Rifampicin
  • Pyrazinamide
  • Ethambutol
  • and Streptomycin

are those drugs that generally have the greatest bactericidal activity when used for TB treatment.

TB treatment for new patients

New patients are those who have no history of prior TB treatment, 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 resistance in new patients, or the patient has developed active TB disease after known contact with a patient documented to have 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 TB treatment. This consists of a two month intensive treatment 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 TB treatment phase.

It is recommended that patients take the TB drugs every day for the six months, although taking them three times a week is possible in some circumstances. It is essential that all the recommended drugs are taken. If only one or two drugs are taken, then the treatment probably won't work, because the TB bacteria that a patient has develops resistance to the drugs. Not only is the patient then still ill, but to be cured they then have to take drugs for the treatment of drug resistant TB, and these drugs are more expensive and have more side effects.

Relapse, failure & recurrence

A patient is said to relapse if they improve whilst on TB treatment, but become ill again after finishing their TB treatment. Patients who experience only a transient improvement whilst on TB drug treatment, or who never respond to treatment, are said to have failed 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, and 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. In any of these situations it must be considered a real possibility that the person has drug resistant TB and their TB drug treatment programme must be decided taking this into account.

Treatment of drug resistant TB

Treatment of multi drug resistant TB (MDR TB) is more difficult than the treatment of drug susceptible TB, and it requires the use of "second line" or reserve drugs that are more costly, cause more side effects, and the drugs must be taken for up to two years. Cure rates for MDR TB are lower, typically ranging from around 50% to 70%.

The drugs that are used for the treatment of drug resistant TB are grouped according to how effective they are, how much experience there is of their use and the drug class. All the "first line" anti TB drugs are in Group 1, apart from streptomcycin which is classified with the other injectable agents in Group 2.

Group 1 : First Line Oral Agents
pyrazinamide
ethambutol
rifabutin
Group 2 : Injectable Agents
kanamycin
amikacin
capreomycin
streptomycin
Group 3 : Fluoroquinolones
levofloxacin
moxifloxacin
ofloxacin
Group 4 : Oral Bacteriostatic Second Line Agents
para–aminosalicylic acid
cycloserine
terizidone
thionamide
protionamide
Group 5 : Agents with an unclear role in the treatment of drug resistant TB
clofazimine
linezolid
amoxicillin/clavulanate
thioacetazone
imipenem/cilastatin
high dose isoniazid
clarithromycin

There is also now the drug Sirturo, previously known as bedaquiline, which in December 2012 was approved by the FDA in the United States, for use in the treatment of drug resistant TB, when no alternatives are available. There is more about Sirturo, which does have some significant side effects.

Deciding on the drugs for the treatment of drug resistant TB

Drug susceptibility testing is testing to find out which TB drugs a person is resistant to, and the availability or not of drug susceptibility testing (DST) in a country or region, and the type of DST available, determines how the drug regimen for a patient with drug resistant TB is decided. That is, which combination of TB drugs should be taken and for how long. Deciding on the right combination of drugs for the treatment of drug resistant TB can often be sufficiently complicated that an algorithm, or formula, will be set by a regional or national TB treatment program. This algorithm is then followed by individual health clinics and health care workers.

If no DST is available at all, and as a result no information is available about which drugs an individual patient is resistant to, then a completely standardized regimen for the treatment of drug resistant TB has to be provided. This can though take into account what is known about local and regional patterns of TB resistance.

If conventional DST, such as culture, is available then some information will become known in due course about the drugs that an individual patient's bacteria is resistant to. However, conventional DST can take many weeks or even months to provide the information, and so initially a standard regimen will have to be provided for the patient. Then when the DST results are known the patient's drugs can be altered as required.

Finally, if rapid DST is available, such as the newer molecular TB tests, then at least some drug resistance information will be available, possibly within a few hours, and certainly within a few days, and so an individualized program of TB treatment can be almost immediately provided for the patient.

TB treatment monitoring

Patients collecting TB drugs

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 treatment. Regular monitoring also helps to ensure that patients complete their treatment, as well as identifying and managing adverse drug reactions. Patients need to have their weight checked every month, and if the patient's weight changes the drug dosages may need to be adjusted.5

When patients have pulmonary TB the patients response to treatment should be monitored using sputum smear microscopy. The recommendation from the World Health Organisation (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. Sputum should be collected when the patient is given the last dose of the intensive phase of treatment.

If the patient has a positive sputum smear at the end of the intensive phase, then there should be a patient assessment carried out, as 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 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.6

Surgery for the treatment of TB

During the early 20th century, surgery played a prominent part in TB management. However after effective TB drugs became available in the mid 20th century the use of surgery declined. Subsequently the emergence of drug resistant TB has led to surgery once again being used as a supplement to drugs for the treatment of TB.

Surgical procedures

Some of the earliest surgical procedures were known collectively as collapse therapies and the aim of these procedures was to deprive the TB bacteria of oxygen.

The use of surgical resection, meaning the removal of part or all of the diseased tissue, in this instance the lung, was used from the 1930s onwards. As techniques were improved surgery became a widely used treatment for TB alongside the development of combination drug treatment. However, as controlled clinical trials increasingly showed that combination treatment for drug susceptibly TB was effective, surgery was no longer routinely used in most countries.

Surgery for the treatment of drug resistant TB

In some countries such as Russia surgical interventions, particularly surgical resection, has continued to be used and as there has globally been more reports of drug resistant TB, so there have been more reports of the use of surgery. Some lung surgery is also now been carried out in India, following the diagnosis in Mumbai of patients with totally drug resistant TB.7

There is however limited good quality data about the effectiveness of using surgery alongside drug treatment for TB, and there is a need for well designed trials to provide more information about the effectiveness of surgery.8

TB treatment - a success

“I am living proof that TB can be beaten, as with TB treatment, patients can be cured; TB untreated is life-theatening. Share the responsibility and share the reward of knowing you are saving lives. Every breath does count, so stop TB now and let people live!”

Archbishop Desmond Tutu, Nobel Laureate9

More about the drugs for TB treatment

More information about individual TB drugs, as well as new TB drugs currently being developed, can be found on the page about TB drugs.

References

  1. "Treatment of Tuberculosis guidelines", WHO, Geneva, 2011, 29 www.who.int/tb/en/
  2. "Treatment of Tuberculosis guidelines", WHO, Geneva, 2010, 85 www.who.int/tb/publications/tb_treatmentguidelines/
  3. "The Global Plan to Stop TB", WHO, Geneva, 2011, vi www.stoptb.org/global/plan/
  4. Based on Lambregts-van Weezenbeck, C. S. "Control of drug-resistant tuberculosis" Tubercle and Lung Disease, (1995) 76, 455
  5. "Treatment of Tuberculosis guidelines", WHO, Geneva, 2010, 85 www.who.int/tb/publications/tb_treatmentguidelines/
  6. "Early tuberculosis treatment monitoring by Xpert MTB/RIF", European Respiratory Journal, May 1 2012 //erj.ersjournals.com/content/39/5/1269.extract#
  7. Sumitra, Roy "No cases of deadliest TB strain in Mumbai", The Times of India, April 17, 2013 //articles.timesofindia.indiatimes.com/2013-04-17/mumbai/38615454_1_tb-patients-xxdr-drug-resistant
  8. "Surgical treatment of drug-resistant tuberculosis" The Lancet Infectious Diseases, February 2012 www.thelancet.com/journals/laninf/article/
  9. Archbishop Desmond Tutu, Speaking at the second Stop TB Partners' Forum, March 2004

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