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Education Materials > Publications > Self-Study Modules on TB > Module 4 > Treatment of TB Disease

Self-Study Modules on Tuberculosis

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Module 4: Treatment of Tuberculosis Infection and Disease

Treatment of TB Disease

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.

TB disease must be treated for at least 6 months; in some cases, treatment lasts even longer. Most of the tubercle bacilli are killed during the first 8 weeks of treatment (the initial phase). However, a few bacilli become dormant (inactive), and they can remain dormant for a long time. The drugs used to treat TB do not work as well against dormant bacilli as they do against bacilli that are growing (active). Therefore, treatment must be continued for several more months to kill these few remaining bacilli (the continuation phase). If treatment is not continued for a long enough time, some bacilli may survive and cause TB disease at a later time (relapse).

In most areas of the country, the initial regimen for treating TB disease should include four drugs (Figure 4.1):

  • Isoniazid (INH)
  • Rifampin (RIF)
  • Pyrazinamide (PZA)
    and either
  • Ethambutol (EMB) or streptomycin (SM)

When the drug susceptibility results are available, clinicians may change the regimen accordingly. In areas where less than 4% of cases are resistant to isoniazid (first drug susceptibility test only), three drugs (INH, RIF, and PZA) may be adequate for the initial regimen.

Figure 4.1 Drugs used to treat TB disease. From left to right: isoniazid, rifampin, pyrazinamide, and ethambutol. Streptomycin (not shown) is given by injection. This is a photograph of drugs used to treat TB disease, including isoniazid, rifampin, pyrazinamide, and ethambutol.

Preventing Drug Resistance

Drug resistance can develop when patients are prescribed an inappropriate regimen for treatment. TB disease must be treated with at least two drugs to which the bacilli are susceptible. Using only one drug to treat TB disease can create a population of tubercle bacilli that is resistant to that drug. When two or more drugs are used together, each drug helps prevent the emergence of bacilli that are resistant to the other drugs. When a patient is not improving in response to a prescribed regimen, adding a single drug to that regimen may have the same effect as using only one drug for treatment: it can lead to drug resistance.

Drug resistance can also develop when patients do not follow treatment regimens as prescribed -- in other words, if they do not take all of their pills, if they do not take their pills as often as prescribed, or both. When this happens, the patients may expose the bacilli to a single drug.
 

Study Questions 4.13-4.16

4.13. Why must TB disease be treated for at least 6 months?

4.14. Which four drugs are recommended for the initial treatment of TB disease?

4.15. Why should at least two drugs be used to treat TB disease?

4.16. Name two factors that can lead to drug resistance.

Answers

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.

Another way to improve patient adherence is to offer incentives or enablers. Incentives are small rewards given to patients to encourage them to take their own medicines or to keep their DOT or clinic appointments. For example, patients may be given food, restaurant coupons, clothing, or other items as an incentive. Enablers are things that help the patient receive treatment, such as bus tokens to get to the clinic. Incentives and enablers should be chosen according to the patient's needs, and they are frequently offered along with DOT.

An important part of helping patients take their medicine is to educate them about TB. This means talking to them about the cause of TB, the way TB is spread, the methods of diagnosing TB, and the specific treatment plan. Patients who understand these concepts are more likely to adhere to treatment.

In summary, in order to prevent relapse and drug resistance, clinicians must prescribe an adequate regimen and make sure that patients adhere to treatment.

Treatment Regimens

There are several options for daily and intermittent treatment. The recommended regimens are described in Table 4.2; the recommended dosages for the most common drugs are listed in Table 4.3. These tables are provided for you to use as a reference.
 

Table 4.2
6-Month Regimen Options1
for Pulmonary and Extrapulmonary TB in Adults and Children
  Initial Phase Continuation Phase Comments
Drugs Interval and Duration Drugs Interval and Duration
1 INH
RIF
PZA
EMB2 or SM
Daily for 8 weeks INH
RIF
Daily or 2 or 3 times weekly3 for 16 weeks4 EMB or SM should be continued until susceptibility to INH and RIF is shown.

In areas where less than 4% of cases are resistant to INH (first drug susceptibility test only), EMB or SM may not be necessary for patients with no individual risk factors for drug resistance.

2 INH
RIF
PZA
EMB2 or SM
Daily for 2 weeks, then

2 times weekly3 for 6 weeks

INH
RIF
2 times weekly3 for 16 weeks4 Patients prescribed this regimen should be given directly observed therapy.

After the initial phase, EMB or SM should be continued until susceptibility to INH and RIF is shown, unless drug resistance is unlikely.

3 INH
RIF
PZA
EMB2 or SM
3 times weekly3 for 6 months4 Patients prescribed this regimen should be given directly observed therapy.

Continue all four drugs for 6 months.5

This regimen has been shown to be effective for INH-resistant TB.

Note. If a patient's drug susceptibility results show resistance to INH, RIF, PZA, EMB, or SM, or if the patient has symptoms, positive smears, or positive cultures after 3 months, consult a TB medical expert.

  1. For adults who have smear- and culture-negative pulmonary TB and for adults and children for whom PZA is contraindicated, different regimen options are necessary. Consult a medical expert for further information.
  2. Ethambutol is not recommended for children who are too young to be monitored for changes in their vision. However, ethambutol should be considered for all children who have TB that is resistant to other drugs but susceptible to ethambutol.
  3. All patients prescribed an intermittent regimen should be given directly observed therapy.
  4. For infants and children with miliary TB, bone and joint TB, or TB meningitis, treatment should last at least 12 months. For adults with these forms of extrapulmonary TB, the patient's response to therapy should be monitored closely. If response is slow or inadequate, treatment may be prolonged on a case-by-case basis.
  5. There is some evidence that SM may be discontinued after 4 months if the isolate is susceptible to all drugs.

INH = isoniazid, RIF = rifampin, PZA = pyrazinamide, SM = streptomycin, EMB = ethambutol
 

Table 4.3
Dosage Recommendations for the Treatment of TB
in Children1 and Adults
Drug Dose in mg/kg
(maximum dosage in parentheses)
Daily 2 times/week2 3 times/week2
Children Adults Children Adults Children Adults
Isoniazid (INH) 10-20
(300 mg)
5
(300 mg)
20-40
(900 mg)
15
(900 mg)
20-40
(900 mg)
15
(900 mg)
Rifampin (RIF) 10-20
(600 mg)
10
(600 mg)
10-20
(600 mg)
10
(600 mg)
10-20
(600 mg)
10
(600 mg)
Pyrazinamide (PZA)3 15-30
(2 gm)
15-30
(2 gm)
50-70
(4 gm)
50-70
(4 gm)
50-70
(3 gm)
50-70
(3 gm)
Ethambutol (EMB)4 15-25 15-25 50 50 25-30 25-30
Streptomycin (SM)3 20-40
(1 gm)
15
(1 gm)
25-30
(1.5 gm)
25-30
(1.5 gm)
25-30
(1.5 gm)
25-30
(1.5 gm)

Note. Doses based on weight must be adjusted as the patient's weight changes.

  1. Children younger than 12 years old.
  2. All patients prescribed an intermittent regimen should be given directly observed therapy.
  3. Pyrazinamide and streptomycin should not be used to treat pregnant women.
  4. Ethambutol is not recommended for children who are too young to be monitored for changes in their vision. However, ethambutol should be considered for all children who have TB that is resistant to other drugs but susceptible to ethambutol.

Special Situations

People with HIV infection. The treatment regimens in Table 4.2 are also effective for people with HIV infection. However, HIV-infected people should be closely monitored for their response to treatment. If they do not seem to be responding to treatment, they should be reevaluated.

People with extrapulmonary TB. In general, regimens that are adequate for treating pulmonary TB are also effective for treating extrapulmonary TB. However, infants and children with miliary TB, bone and joint TB, or TB meningitis should receive at least 12 months of treatment.

Pregnant women. Treatment should not be delayed for pregnant women who have TB disease; rather, it should begin as soon as TB is diagnosed. The preferred initial regimen for pregnant women who have TB is isoniazid, rifampin, and ethambutol for at least 9 months. In most cases, pyrazinamide should NOT be used because there is not enough information about how this drug affects the fetus. Streptomycin should NOT be used because it has been shown to have harmful effects on the fetus.

Children. The treatment of TB is essentially the same for children and adults. However, ethambutol generally is not recommended for children who are too young to be monitored for changes in their vision. (Streptomycin should be used instead.) Also, infants and children with miliary TB, bone and joint TB, or TB meningitis should receive at least 12 months of treatment. Infants who are suspected of having TB should be treated immediately because they are likely to develop life-threatening forms of TB very soon after infection.

Alternative Regimens

People with isoniazid-resistant TB. Isoniazid-resistant TB can be treated with the recommended 6-month, four-drug regimen. It can also be treated with rifampin and ethambutol for 12 months. The treatment of drug-resistant TB should be done under the supervision of a medical expert who is familiar with the treatment of drug-resistant TB.

People with TB resistant to isoniazid and rifampin (multidrug-resistant TB). It is more difficult to treat multidrug-resistant TB than it is to treat drug-susceptible TB. More drugs are required to treat multidrug-resistant TB, and these drugs are less effective and more likely to cause adverse reactions. When TB is resistant to isoniazid and rifampin, treatment can last 2 years or longer. As a last resort, some patients with multidrug-resistant TB undergo surgery to remove part of the infected site.
 

Study Questions 4.17-4.18

4.17. What is directly observed therapy? Why should it be considered for all patients?

4.18. In what special situations should treatment for TB disease last longer than the usual course of treatment?

Answers


 

Case Study 4.3

An 18-month-old girl is admitted to the hospital because of meningitis. Doctors discover that her grandmother had pulmonary TB and was treated with a 6-month regimen. The medical evaluation of the child confirms the diagnosis of TB meningitis.

How long should the child be treated?

Answer

Monitoring for Adverse Reactions

Before starting treatment, adult patients should have certain blood tests and vision tests to help detect any abnormalities that may complicate treatment. For children, only vision tests are necessary unless there are other medical conditions that may complicate treatment. Follow-up tests should be done periodically if the results of the baseline tests indicate abnormalities or if the patient has symptoms that may be due to adverse reactions.

As with patients receiving preventive therapy, all patients being treated for TB disease should be educated about the symptoms that are caused by adverse reactions to the drugs they are taking (Table 4.4). The patients should be warned about the symptoms of insignificant side effects, such as the orange discoloration of the urine from rifampin, as well as the symptoms of potentially serious side effects, such as vomiting or abdominal pain. Patients should be instructed to seek medical attention immediately if they have symptoms of a serious side effect.

All patients should be seen by a clinician at least monthly during treatment and evaluated for possible adverse reactions. During this evaluation, clinicians should ask patients whether they have any of the symptoms that may be due to adverse reactions and examine patients for signs of possible adverse reactions. Also, public health workers who have regular contact with patients should ask patients about adverse reactions at every visit. If a patient has symptoms of an adverse reaction, the public health worker should

  • Instruct the patient to stop the medication if the symptoms are serious (before working with TB patients, public health workers should be educated about which symptoms are serious)
  • Report the situation to a clinician and arrange for a medical evaluation right away
  • Note the symptoms on the patient's form

 
Table 4.4
Common Adverse Reactions to TB Drugs
Caused by Adverse Reaction Signs and Symptoms
Any drug Allergic reactions Skin rash
Ethambutol Eye damage Blurred or changed vision
Changed color vision
Isoniazid
Pyrazinamide
Rifampin
Hepatitis Abdominal pain
Abnormal liver function test results
Dark urine
Fatigue
Fever for 3 or more days
Flulike symptoms
Lack of appetite
Nausea
Vomiting
Yellowish skin or eyes
Isoniazid Nervous system damage Dizziness
Tingling or numbness around the mouth
Peripheral neuropathy Tingling sensation in hands and feet
Pyrazinamide Stomach upset Stomach upset, vomiting, lack of appetite
Increased uric acid Abnormal uric acid level
Joint aches
Gout (rare)
Rifampin Bleeding problems Easy bruising
Slow blood clotting
Discoloration of body fluids Orange urine, sweat, or tears
Permanently stained soft contact lenses
Drug interactions Interferes with certain medications, such as birth control pills, birth control implants, and methadone treatment
Sensitivity to the sun Frequent sunburn
Streptomycin Ear damage Balance problems
Hearing loss
Ringing in the ears
Kidney damage Abnormal kidney function test results

 

Study Questions 4.19-4.20

4.19. Name the drug or drugs that may cause each of the following symptoms or adverse reactions.

Ear damage:

Hepatitis:

Eye damage:

Orange discoloration of the urine:

4.20. How often should patients be monitored for adverse reactions to TB drugs?

Answers


 

Case Study 4.4

You are assigned to deliver medications to TB patients as part of the directly observed therapy program where you work. When you visit Mr. Jackson's house, you ask him how he is feeling. He tells you that he was up all night vomiting.

What are the possible causes?

Answer


 

Case Study 4.5

Ms. Young, a patient who started treatment for TB disease last week, calls the TB clinic to complain that her urine has changed to a funny color.

Name two possible causes, and explain how each would affect the color of the urine.

Answer

Monitoring Patients' Adherence to Therapy

Patients who are not receiving directly observed 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
  • 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
  • Assess the patient's clinical response to treatment

None of these methods can be used to prove that a patient is taking every dose of the prescribed medication. The best way to ensure adherence to treatment is to use directly observed therapy.

Evaluating Patients' Response to Treatment

Clinicians use three methods to determine whether a patient is responding to treatment. First, they can check to see whether the patient still has symptoms of TB (clinical evaluation). Although each patient responds to treatment at a different pace, all patients' TB symptoms should gradually improve and eventually go away. Patients whose symptoms do not improve during the first 2 months of treatment, or whose symptoms worsen after improving initially, should be reevaluated.

Public health workers who have regular contact with patients should pay attention to the patients' improvement. If a patient has symptoms of TB (or of adverse reactions), they should report the situation to the clinician and arrange for a medical evaluation right away. They should also note the symptoms on the patient's forms.

Second, clinicians can check a patient's response to treatment by doing a bacteriologic examination of the sputum or other specimens. Specimens should be examined at least every month until the culture results have converted from positive to negative. For more than 85% of patients who are treated with isoniazid and rifampin, cultures will convert to negative after the patient has received 2 months of treatment. After conversion is documented, patients should have at least one more smear examination and culture at the end of treatment. Any patient whose culture results have not become negative after 2 months of treatment, or whose culture results become positive after being negative, should be carefully reevaluated.

Third, clinicians can use x-rays to monitor a patient's response to treatment. Repeated x-rays are not as important as monthly bacteriologic and clinical evaluations. However, patients should have an x-ray at the end of treatment. This x-ray can be compared with any x-rays given later on. X-rays are also useful for patients who have negative culture results before treatment or who have certain types of extrapulmonary TB, such as bone and joint TB. In these patients, the bacteriological response may be difficult to assess, and the clinician may have to rely on the clinical and x-ray responses.

The tuberculin skin test cannot be used to determine whether a patient is responding to treatment. This is because most people who have a positive skin test reaction will have a positive reaction if they are skin tested later in their lives, regardless of whether they have received treatment (see Module 3, Diagnosis of Tuberculosis Infection and Disease).

Reevaluating Patients Who Do Not Respond to Treatment or Who Relapse

Patients should be reevaluated promptly if their

  • Symptoms do not improve during the first 2 months of therapy
  • Symptoms worsen after improving initially
  • Culture results have not become negative after 2 months of treatment
  • Culture results become positive after being negative

Reevaluating the patient means checking for drug resistance by repeating the drug susceptibility tests and assessing whether the patient has been taking medication as prescribed.

The treatment of TB can be complicated, especially in patients who fail to respond to treatment, who relapse, or who have drug-resistant TB or adverse reactions to medications. A new regimen may be required, and treatment may last longer. Clinicians who do not have experience with these situations should consult a medical expert.
 

Study Questions 4.21-4.25

4.21. Name four ways that clinicians can assess whether a patient is adhering to treatment.

4.22. What is the best way to ensure that a patient adheres to treatment?

4.23. How can clinicians determine whether a patient is responding to treatment?

4.24. Under what circumstances should patients be reevaluated?

4.25. What does reevaluating the patient mean?

Answers


 

Case Study 4.6

Mr. Vigo was diagnosed with smear-positive pulmonary TB in January. He was treated with isoniazid, rifampin, and pyrazinamide by his private physician. He visited his physician again in March. His drug susceptibility test results were not available at the time of this appointment. Nevertheless, the physician discontinued his prescription of pyrazinamide and gave him refills of isoniazid and rifampin. Mr. Vigo visited his physician again in April. He had a persistent cough, and his sputum smear was found to be positive.

What should be done next?

Answer

What Is the Role of the Public Health Worker in TB Treatment?

Public health workers in TB programs and other facilities play an important role in helping patients complete preventive therapy or treatment for TB disease. Many public health workers provide directly observed therapy (DOT) or have regular contact with TB patients in clinics, nursing homes, drug treatment centers, or other facilities. At each visit with a patient, public health workers should look for signs and symptoms of adverse reactions to the medication. For this reason, public health workers must be familiar with the signs and symptoms of adverse reactions to the drugs commonly used to treat TB. If a patient has symptoms of an adverse reaction, the public health worker should

  • Instruct the patient to stop the medication if the symptoms are serious (before working with TB patients, public health workers should be educated about which symptoms are serious)
  • Report the situation to a clinician and arrange for a medical evaluation right away
  • Note the symptoms on the patient's form

Also, public health workers can help monitor a patient's response to treatment for TB disease by looking for symptoms of TB disease. Patients receiving treatment for TB disease usually have symptoms at the beginning of therapy, such as coughing, fatigue, and fever. These symptoms should gradually improve and eventually go away. At each visit with a patient, public health workers should pay attention to the patient's improvement. If a patient has symptoms of TB, public health workers should

  • Report the situation to a clinician and arrange for a medical evaluation right away
  • Note the symptoms on the patient's form

In addition to providing DOT, public health workers may be responsible for locating patients who have missed DOT visits or clinic appointments and helping them return to treatment. They may also educate patients and their families about TB, serve as interpreters, arrange and provide transportation for patients, and refer patients to other social services as needed. Finally, in many areas public health workers work with physicians in private practice (physicians who do not work in the health department) to make sure that their TB patients complete an adequate regimen for TB treatment.
 

Study Questions 4.26

4.26. What should a public health worker do if he or she notices that a patient has symptoms of an adverse reaction?

Answer


 

Case Study 4.7

Ms. DeVonne began treatment for pulmonary TB disease 2 months ago, at the beginning of September. You have been giving her directly observed therapy. During the first few weeks of therapy, you noticed that Ms. DeVonne's symptoms were improving a little. However, at a visit in October, you see that Ms. DeVonne is coughing up blood, and she tells you that she feels like she has a fever.

What should you do?

Answer

 

 


Released October 2008
Centers for Disease Control and Prevention
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