Tuberculosis (TB) is a disease caused by bacteria that are spread from person to person through the air. TB usually affects the lungs, but it can also affect other parts of the body, such as the brain, the kidneys, or the spine. In most cases, TB is treatable and curable; however, people with TB can die if they do not get proper treatment. Sometimes drug-resistant TB occurs when bacteria become resistant to the drugs used to treat TB. This means that the drug can no longer kill the TB bacteria.

Drug-resistant TB (DR TB) is spread the same way that drug-susceptible TB is spread. TB is spread through the air from one person to another. The TB bacteria are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings. People nearby may breathe in these bacteria and become infected.

Drug-resistant TB can occur when the drugs used to treat TB are misused or mismanaged. Examples of misuse or mismanagement include

• People do not complete a full course of TB treatment
• Health care providers prescribe the wrong treatment (the wrong dose or length of time)
• Drugs for proper treatment are not available
• Drugs are of poor quality

Drug-resistant TB is more common in people who

• Do not take their TB drugs regularly
• Do not take all of their TB drugs
• Develop TB disease again, after being treated for TB disease in the past
• Come from areas of the world where drug-resistant TB is common
• Have spent time with someone known to have drug-resistant TB disease

Multidrug-Resistant TB (MDR TB)

Multidrug-resistant TB (MDR TB) is caused by TB bacteria that are resistant to at least isoniazid and rifampin, the two most potent TB drugs. These drugs are used to treat all persons with TB disease.

TB experts should be consulted in the treatment of MDR TB.

Pre-Extensively Drug-resistant TB (pre-XDR TB)

Pre-Extensively Drug-resistant TB (pre-XDR TB) is a type of MDR TB caused by TB bacteria that are resistant to isoniazid, rifampin, and a fluroquinolone OR by TB bacteria that are resistant to isoniazid, rifampin, and a second-line injectable (amikacin, capreomycin, and kanamycin).

Extensively Drug-resistant TB (XDR TB)

Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB caused by TB bacteria that are resistant to isoniazid and rifampin, a fluroquinolone, and a second-line injectable (amikacin, capreomycin, and kanamycin) OR by TB bacteria that are resistant to isoniazid, rifampin, a fluroquinolone, and bedaquiline or linezolid.

Because XDR TB is resistant to the most potent TB drugs, patients are left with treatment options that are much less effective.

XDR TB is of special concern for people with HIV infection or other conditions that can weaken the immune system. These people are more likely to develop TB disease once they are infected, and also have a higher risk of death once they develop TB.

TB experts should be consulted in the treatment of XDR TB.

What is Extensively Drug-Resistant Tuberculosis (XDR TB)?

Extensively drug-resistant TB (XDR TB) is a rare type of multidrug-resistant tuberculosis (MDR TB) that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). MDR TB is caused by an organism that is resistant to at least isoniazid and rifampin, the two most potent TB drugs.

How is XDR TB spread?

Drug-susceptible TB and XDR TB are spread the same way. TB bacteria are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, shouts, or sings. These bacteria can float in the air for several hours, depending on the environment. Persons who breathe in the air containing these TB bacteria can become infected.

TB is not spread by

• shaking someone’s hand
• sharing food or drink
• touching bed linens or toilet seats
• sharing toothbrushes
• kissing

Why is XDR TB so serious?

Because XDR TB is resistant to the most potent TB drugs, the remaining treatment options are less effective, have more side effects, and are more expensive. XDR TB is of special concern for persons with HIV infection or other conditions that can weaken the immune system. These persons are more likely to develop TB disease once they are infected, and they also have a higher risk of death if they develop TB disease.

Who is at risk for getting XDR TB?

Drug-resistant TB (MDR or XDR) is more common in people who:

• Do not take their TB medicine regularly
• Do not take all of their TB medicines as prescribed by their doctor
• Develop TB disease again, after having taken TB medicine in the past
• Come from areas of the world where drug-resistant TB is common
• Have spent time with someone known to have drug-resistant TB disease

How can I prevent myself from getting TB?

Avoid close contact for a prolonged period of time with known TB patients in crowded, enclosed environments like clinics, hospitals, prisons, or homeless shelters.

Can the TB vaccine (BCG) help prevent XDR TB?

The TB vaccine is called Bacille Calmette-Guérin (BCG), and it is used in many countries to prevent severe forms of TB in children. However, BCG is not generally recommended in the United States because it has limited effectiveness for preventing the most common forms of TB and in preventing TB in adults. The effect of BCG against XDR TB would likely be similar to the effect on drug-susceptible TB.

If I have drug-susceptible TB, how can I prevent getting drug-resistant TB?

The most important thing is for you to continue taking all your TB medicines exactly as prescribed. No doses should be missed and treatment should not be stopped early. You should tell your health care provider if you are having trouble taking the medications or if you have any side effects. If you plan to travel, talk with your health care provider, and make sure you have enough medicine to last while away.

Can XDR TB be treated and cured?

Yes, in some cases. Some TB control programs have shown that cure is possible for an estimated 30% to 50% of affected people. Successful outcomes depend greatly on the extent of the drug resistance, the severity of the disease, whether the patient’s immune system is weakened, and adherence to treatment.

What are the symptoms of XDR TB?

The general symptoms of TB disease include feelings of sickness or weakness, weight loss, fever, and night sweats. The symptoms of TB disease of the lungs may also include coughing, chest pain, and coughing up blood. Symptoms of TB disease in other parts of the body depend on the area affected. If you have these symptoms, you should contact your doctor or local health department.

What should I do if I have been around someone who has XDR TB?

If you think you have been exposed to someone with XDR TB disease, you should contact your doctor or local health department about getting a TB skin test or blood test for TB infection. You should tell the doctor or nurse when you spent time with this person. You should also tell the doctor or nurse where the person with XDR TB is being treated. It will be important to know about this person’s treatment. If your test for TB infection is positive, you will need special follow up.

How long does it take to find out if you have XDR TB?

If TB bacteria are found in the sputum (phlegm), the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible TB and drug-resistant TB. To determine drug susceptibility, the bacteria need to be grown and tested in a specialized laboratory. Final diagnosis for TB, and especially for XDR TB, may take from 6 to 16 weeks.

Is XDR TB a problem in the United States?

The risk of acquiring XDR TB in the United States appears to be low because XDR TB is uncommon in the U.S. However, TB can spread easily. As long as XDR TB exists, the risk to people in the United States is not zero, and the U.S. public health system must address the threat.

How many cases of XDR TB have been reported in the United States?

In the United States, 63 cases of XDR TB have been reported between 1993 and 2011*.

*The National Tuberculosis Surveillance System (NTSS) 1993-2011.

Is it safe to travel to countries where cases of XDR TB have been reported?

Although MDR and XDR TB are occurring globally, they are still rare. HIV-infected travelers are at greatest risk if they come in contact with a person with MDR or XDR TB.

All travelers should avoid high risk settings where there are no infection control measures in place. Documented places where transmission has occurred include crowded hospitals, prisons, homeless shelters, and other settings where susceptible persons come in contact with persons with TB disease.

What can health care providers do to prevent XDR TB?

Health care providers can help prevent MDR and XDR TB by quickly diagnosing TB cases, following recommended treatment guidelines, monitoring patients’ response to treatment, and making sure therapy is completed.

Providers should also ensure proper implementation of infection control procedures to prevent exposure to TB in hospitals or health-care settings where TB patients are likely to be seen.

Why does there seem to be more cases of XDR TB now than there were in the past?

In 2006, CDC, the World Health Organization (WHO), and other global leaders in TB reported the results of a survey regarding drug-resistant TB conducted by 25 reference laboratories comprising the Global Supranational TB Reference Laboratory Network, the National TB Surveillance System in the United States, the national reference laboratory of South Korea, and the national MDR TB patient registry in Latvia. The findings indicated that 20% of M. tuberculosis isolates were MDR, and 2% also were resistant to many additional TB drugs. This highly resistant form of TB was identified in every region of the world where there was lab capacity to identify it. In a report published in 2006, the highly resistant form of TB was named extensively drug-resistant TB (XDR TB). Since then, more countries have improved their laboratory capacity to test for XDR TB and their ability to report XDR TB. These factors have contributed to an apparent increase in drug-resistant TB because of better diagnosis and better reporting.

What is CDC doing to prevent XDR TB from becoming a bigger problem?

CDC is collaborating with other federal agencies and international partners to raise awareness and enhance strategies for TB prevention worldwide by:

• Strengthening TB services for people living with HIV/AIDS;
• Guiding preparedness and outbreak investigation responses;
• Improving access to TB drugs;
• Conducting routine surveillance (including drug susceptibility) and periodic surveys;
• Implementing new, rapid diagnostic tests;
• Developing and promoting, national and international TB testing standards;
• Conducting program evaluation (e.g., National TB Indicators Project [NTIP]);
• Building capacity of health care providers to diagnose and treat TB;
• Reinvigorating the Federal TB Task Force;
• Providing assistance to improve TB program capacity in the U.S. and abroad; and
• Developing education, risk, and media communications (Web- and print-based) to aid in preparedness and public awareness of TB prevention and control issues.

Drug susceptibility testing is a difficult procedure to standardize, and proficiency in performing these tests requires an understanding of many elements, including the

• Origin of drug resistance and the criteria for resistance
• Potency and stability of drugs during laboratory manipulation
• Antimycobacterial activity of drugs when incorporated into different media
• Reading, interpretation, and reporting of results

The LB uses an indirect proportion method for testing M. tuberculosis complex mycobacteria to 12 drugs at 35C on Middlebrook 7H10 agar. The test requires 1 month to complete. Growth on the control medium is compared to the growth on the drug-containing medium to determine susceptibility or resistance. When performed properly, this method allows a quantitation of the proportion of mutants resistant to a drug and can detect the 1% proportion of drug- resistant mutants above which therapeutic failure is likely.

M. tuberculosis complex are tested by this method with the following drugs:

• Isoniazid
• Rifampin
• Ethambutol
• Ciprofloxacin
• Ofloxacin
• Streptomycin
• Kanamycin
• Capreomycin
• Amikacin
• Rifabutin
• Ethionamide
• Para-aminosalicylic acid (PAS)

Pyrazinamide is tested by the MGIT 960 method.

Drug-resistant TB is caused by TB bacteria that are resistant to at least one first-line anti-TB drug. Multidrug-resistant TB (MDR TB) is resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF).

Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

Treating and curing drug-resistant TB is complicated. Inappropriate management can have life-threatening results. Drug-resistant TB should be managed by or in close consultation with an expert in the disease.

Safety Announcement Regarding Fluoroquinolone Antibacterial Drugs

The US Food and Drug Administration (FDA) has advised restricting fluoroquinolone antibiotic use for certain uncomplicated infections because of adverse effects from these medications (available at http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm). Specifically, FDA indicated that the risks of adverse effects of fluoroquinolone antibacterial drugs generally outweigh the benefits for patients with sinusitis, bronchitis, and uncomplicated urinary tract infections who have other treatment options.

While patients receiving fluoroquinolone antibacterial drugs for tuberculosis (TB) also have a chance of experiencing the adverse effects noted by FDA, fluoroquinolone antibacterial drugs are absolutely necessary for some patients who have drug-resistant TB disease or drug-resistant latent TB infection or who cannot tolerate first-line TB drugs. For these TB patients, there are no better alternatives, and the benefits of fluoroquinolone antibacterial drugs outweigh the risks because TB is not a minor infection, but potentially fatal or debilitating.

If you are a TB patient receiving fluoroquinolone antibacterial drugs and have questions, please contact your medical provider or local or state TB control program. If you are a medical provider and have questions about the use of fluoroquinolone antibacterial drugs in TB treatment, please contact your local or state TB control program.

The most important way to prevent the spread of drug-resistant TB is to take all TB drugs exactly as prescribed by the health care provider. No doses should be missed and treatment should not be stopped early. People receiving treatment for TB disease should tell their health care provider if they are having trouble taking the drugs.

Health care providers can help prevent drug-resistant TB by quickly diagnosing cases, following recommended treatment guidelines, monitoring patients’ response to treatment, and making sure therapy is completed.

Another way to prevent getting drug-resistant TB is to avoid exposure to known drug-resistant TB patients in closed or crowded places such as hospitals, prisons, or homeless shelters. People who work in hospitals or health-care settings where TB patients are likely to be seen should consult infection control or occupational health experts.

TB disease – an illness in which TB bacteria are multiplying and attacking a part of the body, usually the lungs The symptoms of TB disease include weakness, weight loss, fever, no appetite, chills, and sweating at night. Other symptoms of TB disease depend on where in the body the bacteria are growing. If TB disease is in the lungs (pulmonary TB), the symptoms may include a bad cough, pain in the chest, or coughing up blood. A person with TB disease may be infectious and spread TB bacteria to others.

BCG – a vaccine for TB named after the French scientists who developed it, Calmette and Guérin. BCG is rarely used in the United States, but it is often given to infants and small children in other countries where TB is common.

Chest x-ray – a picture of the inside of your chest. A chest x-ray is made by exposing a film to x-rays that pass through the chest. A doctor can look at this film to see whether TB bacteria have damaged the lungs.

Contact – a person who has spent time with a person with infectious TB.

Culture – a test to see whether there are TB bacteria in your phlegm or other body fluids. This test can take 2 to 4 weeks in most laboratories.

Directly observed therapy (DOT) – a way of helping patients take their medicine for TB. If you get DOT, you will meet with a health care worker every day or several times a week. You will meet at a place you both agree on. This can be the TB clinic, your home or work, or any other convenient location. You will take your medicine while the health care worker watches.

Extensively drug-resistant TB (XDR TB) – XDR TB is a rare type of TB disease that is resistant to nearly all medicines used to treat TB.

Extrapulmonary TB – TB disease in any part of the body other than the lungs (for example, the kidney, spine, brain, or lymph nodes).

HIV infection – infection with the human immunodeficiency virus, the virus that causes AIDS (acquired immunodeficiency syndrome). A person with both latent TB infection and HIV infection is at very high risk for developing TB disease.

Isoniazid (INH) – a medicine used to prevent TB disease in people who have latent TB infection. INH is also one of the four medicines often used to treat TB disease.

Latent TB infection – a condition in which TB bacteria are alive, but inactive in the body. People with latent TB infection have no symptoms, don’t feel sick, can’t spread TB to others, and usually have a positive TB skin test or positive TB blood test reaction. But they may develop TB disease if they do not receive treatment for latent TB infection.

Multidrug-resistant TB (MDR TB) – TB disease caused by bacteria resistant to two of the most important medicines: INH and RIF.

Mycobacterium tuberculosis – bacteria that cause latent TB infection and TB disease.

Negative – usually refers to a test result. If you have a negative TB skin test reaction or negative TB blood test reaction, you probably do not have TB infection.

Positive – usually refers to a test result. If you have a positive TB skin test reaction or positive TB blood test reaction, you probably have TB infection.

Pulmonary TB – TB disease that occurs in the lungs, usually producing a cough that lasts 3 weeks or longer. Most TB disease is pulmonary.

Resistant bacteria – bacteria that can no longer be killed by a certain medicine.

Rifampin (RIF) – one of the four medicines often used to treat TB disease. It is considered a first-line drug.

Rifapentine (RPT) – one of two medicines used to treat latent TB infection.

Smear – a test to see whether there are TB bacteria in your phlegm. To do this test, lab workers smear the phlegm on a glass slide, stain the slide with a special stain, and look for any TB bacteria on the slide. This test usually takes 1 day to get the results.

Sputum – phlegm coughed up from deep inside the lungs. Sputum is examined for TB bacteria using a smear; part of the sputum can also be used to do a culture.

TB blood test – a test that uses a blood sample to find out if you are infected with TB bacteria. The test measures the response to TB proteins when they are mixed with a small amount of blood. Examples of these TB blood tests include QuantiFERON-TB Gold In-tube (QFT-GIT) and T-Spot.TB test.

TB disease – an illness in which TB bacteria are multiplying and attacking a part of the body, usually the lungs. The symptoms of TB disease include weakness, weight loss, fever, no appetite, chills, and sweating at night. Other symptoms of TB disease depend on where in the body the bacteria are growing. If TB disease is in the lungs (pulmonary TB), the symptoms may include a bad cough, pain in the chest, and coughing up blood. A person with TB disease may be infectious and spread TB bacteria to others.

TB skin test – a test that is often used to find out if you are infected with TB bacteria. A liquid called tuberculin is injected under the skin on the lower part of your arm. If you have a positive reaction to this test, you probably have TB infection. Other tests will be needed to find out if you have latent TB infection or TB disease.

Tuberculinor PPD – a liquid that is injected under the skin on the lower part of your arm during a TB skin test. If you have latent TB infection, you will probably have a positive reaction to the tuberculin.