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CDC 24/7 – Saving Lives. Protecting People. Saving Money Through Prevention. Learn More About How CDC Works For You…

Protecting the Public's Health against Tuberculosis: Moving Forward

Published: July 26, 2007

We share in the optimism associated with the recent news that indicates patients originally identified with extensively drug-resistant tuberculosis (XDR TB) may have additional drug treatment options. Yet, the reality remains that these patients and many others across the world are suffering from a very serious form of multi-drug resistant tuberculosis (MDR TB). Drug-resistant TB poses a grave and growing threat to global public health which we as a nation must take action to address.

We must ensure that the public health messages and necessary responses to drug-resistant tuberculosis are not quickly forgotten, but rather propel us toward new solutions. First, it is critical that we ensure that the public understand the basic facts about how this disease evolves, how it is transmitted, and how to protect their own health and that of others. Like many infectious diseases, tuberculosis takes weeks to months to identify or diagnose, is challenging to treat and can sometimes be spread by people who don't appear to be ill. The challenging nature of TB also means that effectively treating it, and preventing its transmission, requires a sustained partnership between health care providers, local and state public health practitioners and patients infected with the disease.

Second, it is worth reiterating that anyone with active TB disease, regardless of whether it is drug-resistant, should avoid situations that place them in prolonged contact with others, including flying on commercial aircraft. TB is generally not spread by casual contact, but typically requires relatively prolonged contact in shared airspace. The environment on long flights in commercial aircraft, particularly those of eight or more hours in length, has been previously implicated in TB transmission, especially to passengers seated in close proximity. This is the basis for the World Health Organization (WHO) guidelines for the prevention of TB transmission during air travel. Protecting the health of international air travelers requires building and sustaining partnerships between public health and infected individuals.

Third, in moving forward, we need to increase our efforts to communicate strongly and clearly about risks posed by tuberculosis; strengthen our efforts to reduce the fear and stigma associated with this devastating disease; and clarify and reinforce the roles that patients, clinicians, and public health officials play in infectious disease control.

There's no doubt we have had considerable success in TB prevention and control in the United States. There's also no doubt the increasing prevalence of drug-resistant tuberculosis bacteria across the world is a reminder that much more needs to be done. Beyond improved awareness and education, scientific advances will also be required to reduce the threat of this disease. The current methods to diagnose TB are complex, are not available everywhere they are needed, and require far too much time to provide results. New methods are needed that can give us reliable answers in hours or days instead of weeks. Similarly, new safe and effective vaccines and treatments are urgently needed to combat drug-resistant TB bacteria to prevent a return to the pre-antibiotic era.

Effective public health response to MDR and XDR TB requires accelerated efforts and earnest engagement by multiple sectors of society. All of us—patients, providers, health officials, and policymakers—share a responsibility to take action now to prevent further transmission.

Martin S Cetron, MD
Captain, U.S. Public Health Service
Director, Global Migration and Quarantine
Centers for Disease Control and Prevention

Kenneth G. Castro, M.D.
Assistant Surgeon General, U.S. Public Health Service
Director, Tuberculosis Elimination
Centers for Disease Control and Prevention

Q&A Related to CDC July 3, 2007 Press Conference with National Jewish Medical and Research Center

Press Briefing Transcript

How can drug susceptibility testing have different results on specimens from the same patient?
TB bacteria can show variable resistance to second-line TB medications. Thus, a change or difference in test results can, and does, happen when it comes to MDR and XDR TB. Different specimens/samples from the same person can produce different results. The patient may also be infected with more than one strain of TB. TB that consists of more than one strain is not uncommon. For example, in one recent study, 19% of patients were infected with two different strains of TB at the same time. [Reference: Warren RM et al. Patients with Active Tuberculosis often Have Different Strains in the Same Sputum Specimen. Am J Respir Crit Care Med 2004;169:610-4.]

How do these results affect the follow-up of persons exposed to this patient?
  • The public health response to drug resistant TB infections, whether MDR or XDR, is the same under the World Health Organization's TB and Airline Travel guidelines.
  • It is important to remember that a patient who has drug-resistant TB represents a significant public health concern. MDR-TB is a rare version of TB and is resistant to the most commonly used drug therapies. It is a serious illness that can be transmitted to others, and thus put others at risk for getting a difficult-to-treat disease.
  • People with these infections should not be flying on commercial airlines and if it is discovered that such travel has taken place, an effort should be made to notify and evaluate passengers who were seated near them.
  • CDC continues efforts to ensure the well being of persons who may have been exposed and infected by this patient.
What is multidrug-resistant tuberculosis (MDR TB)?
  • Multidrug-resistant tuberculosis (MDR TB) is TB that is resistant to at least two of the best anti-TB medications, isoniazid and rifampin. These medications are considered first-line drugs and are used to treat all persons with drug-susceptible TB disease.
  • A more serious form of MDR TB is called extensively drug-resistant TB (XDR TB). XDR TB is a relatively rare type of TB that is resistant to nearly all medicines used to treat TB disease. Because XDR TB is resistant to the most effective TB medicines used to treat TB, patients are left with very limited useful treatment options.
  • Treatment for MDR TB is considerably less effective, more toxic, and more expensive than for drug-susceptible TB. MDR TB, as is XDR TB, is a difficult to treat disease that is often fatal.
  • Treatment of MDR TB requires a patient to take 18–24 months of medication, including taking multiple second-line medications, to kill the bacteria.

What is extensively drug resistant tuberculosis (XDR TB)?
XDR TB is a more serious form of multidrug-resistant TB (MDR TB). In both cases, the TB is resistant to the "first-line" antibiotics available for treatment, as well as some of the second-line antibiotics. Both MDR TB and XDR TB, are difficult to treat and are often fatal. XDR TB is defined as TB which is resistant to isoniazid and rifampin, plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). Because XDR TB is resistant to first-line and second-line drugs, patients are left with very limited treatment options that are even less effective than for MDR TB that does not qualify as XDR TB.

What is drug susceptibility testing?
Drug susceptibility testing uses laboratory techniques to determine which medicines will kill the TB bacteria in the patient's specimen. The results of drug susceptibility tests can help clinicians choose the appropriate treatment regimen for each patient.

Why are National Jewish Medical Center's test results different from CDC's results?
  • It is not unusual to have differing drug susceptibility results from multiple specimens from the same patient. Reasons for differing results include
    • The TB bacteria in a sputum specimen may come from different parts of the lung or different lesions in the lung.
    • The TB bacteria in a sputum specimen may have different types of bacteria such as drug-susceptible bacteria (bacteria that can be killed by TB medicines) and drug-resistant (bacteria that cannot be killed by most TB medicines).
    • The amount of the different types of bacteria may vary over time and from specimen to specimen.
  • When drug susceptibility test results from different specimens from one patient are not the same, a treatment regimen is chosen that is most likely to be effective on the most predominant TB bacteria.
  • CDC's laboratory functions as a national and supranational (i.e., for other countries) reference facility to provide access to drug susceptibility testing for second-line drugs.
How is drug susceptibility testing conducted?
  • CDC receives samples of M. tuberculosis that have been obtained from cultures performed in labs outside of CDC (for example, state public health, international, and private laboratories).
  • Before sending samples to CDC, the labs smear cultures on media and keep the cultures warm media until bacteria grow (colonies).
  • Colonies of bacteria are scraped from the surface of the culture media, taking care to sample all parts of this growth (colonies).
  • The colonies are placed into a broth and kept warm for approximately one week.
  • At one week, the broth is diluted to obtain the number of organisms needed to perform susceptibility testing.
  • The diluted broth is spread onto solid agar media in Petri plates (drug plates) that contain the drugs used for tuberculosis. There is also a growth control (a plate with no drug) included.
  • The drug plates and growth control plates are kept warm for 21 days and then examined for growth. The number of colonies on the growth control plate and on each drug plates is determined. A sample is resistant to a drug when the number of colonies that grow on the drug-containing agar are greater than 1% of the colonies that grow on the growth control.
What does CDC do to ensure laboratory quality control for drug susceptibility testing?
  • The CDC drug susceptibility testing is performed using standard techniques with quality control and data review before results are released.
  • CDC uses a standardized inoculum with quality control testing to confirm that the correct drugs and drug concentrations are used.
  • Quality control testing is also performed on the culture media used to grow the TB bacteria to ensure consistency.
  • The CDC laboratory performs M. tuberculosis drug susceptibility testing as described by the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards). Testing is performed and results are reported in compliance with Clinical Laboratory Improvement Amendments (CLIA) regulations.
What are the first- and second-line drugs used to treat TB?
  • When drug susceptibility test results from different specimens from one patient are not the same, a treatment regimen is chosen that is most likely to be effective on the most predominant TB bacteria.
  • There are 10 drugs currently approved by the U.S. Food and Drug Administration (FDA) for treating TB. Of the approved drugs, the first-line anti-TB agents that form the core of treatment regimens include
    • isoniazid (INH)
    • rifampin (RIF)
    • ethambutol (EMB)
    • pyrazinamide (PZA)
  • Second-line drugs used to treat TB include
    • fluoroquinolones (levofloxacin, moxifloxacin, gatifloxacin)
    • three injectable drugs (amikacin, kanamycin, or capreomycin)
    • ethionamide
    • cycloserine
  • Second-line drugs are less effective and more toxic than first-line drugs used to treat TB.

What can be done to improve our ability to prevent and reduce the numbers and cases of TB?
New tools for TB diagnosis, treatment, and prevention are needed to achieve the goal of TB elimination. New diagnostic tools for TB detection, especially drug-resistant TB, are needed. Rapid diagnostic tests, such as those that have been developed for HIV, are still unavailable for drug-resistant TB.

Page last updated: July 26, 2007
Content source: Centers for Disease Control and Prevention
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