XDR-TB and Patient/Community Safety:

Answers to Your Questions about XDR-TB
(Extensively Drug-Resistant Tuberculosis)
and Andrew Speaker

Is there reason for patients, staff or visitors to National Jewish Health to be concerned about XDR-TB or the arrival of Andrew Speaker?

There is absolutely no reason for concern.  National Jewish Health continues to be a safe center of excellence for treatment of patients with this form of tuberculosis.  We have had a number of these types of patients over the years, and have safeguards in place to keep other patients, staff and faculty from becoming exposed to the disease, including appropriate isolation procedures, as required of all TB patients.  No one is at any additional risk of developing this disease because this—or any other—patient receives treatment here.

What is tuberculosis (TB)?

Mycobacterium tuberculosis, the TB organism, is a bacterium, not a virus.  It is typically transmitted from person to person through inhalation of airborne droplets released when an infected person coughs.  The mycobacteria eventually settle in the lungs, where they can either result in progressive infection, or in most cases remain dormant (the inactive state) for years or even decades.  If one’s immune system is subsequently weakened by other diseases or medications, the TB may activate, destroying lung tissue and causing such symptoms as fever, night sweats, persistent cough, weight loss and chronic fatigue.  About 10% of those infected will develop TB in their lifetimes.
Read more about tuberculosis (TB).

Who has TB?

The World Health Organization estimates that one-third of the world's population, 2 billion people, has latent infection with TB.  From this pool, 9 million new cases occur annually.  Case rates are vastly disproportionate by region: less than five cases per 100,000 population annually in the United States ; over 500 cases per 100,000 in parts of South Africa .  Tuberculosis rates are vastly increased with the HIV epidemic because HIV depletes the white blood cells essential for TB immunity.

What is MDR-TB and XDR-TB?

For the past 40 years, TB treatment has entailed giving 3 or 4 medications for periods originally of 15 months, recently down to 6 months.  The multiple-drug approach prevents the escape of naturally-occurring drug-resistant mutants because "drug A" kills mutant strains resistant to "drug B" and vice-versa.  When inadequate regimens are given, such mutations do escape, typically resulting in resistance to one, then several drugs.  Resistance to the 2 major drugs, rifampin and isoniazid, was associated with numerous epidemics around the world in the 1990s; those strains were labeled multi-drug resistant TB, or MDR-TB.

More recently, cases have been recognized with resistance not only to rifampin and isoniazid, but at least two additional critical drugs.  The fluoroquinolones and one or more the injectable agents such as amikacin or capreomycin.  The strains have been dubbed extensively drug-resistant TB or XDR-TB.  A recent epidemic of XDR-TB in South Africa among people with AIDS resulted in rapid death for 52 of 53 patients.

How many people get TB, MDR-TB and XDR-TB each year?

1: CDC.  Reported Tuberculosis in the United States , 2005.
2: WHO. Tuberculosis Fact Sheet. 2006.

How will this patient (Andrew Speaker) with XDR-TB be treated?

As XDR-TB is still a relatively new phenomenon, there is not a clear treatment path.  Doctors at National Jewish Health have begun administering oral and intravenous antibiotics to Mr. Speaker.  Over the next several days they expect to add additional medications as indicated by laboratory testing.   The original choice of antibiotics will be based upon information about drug resistance obtained from the U.S. Centers for Disease Control and Prevention. 

Can XDR-TB be cured?

In a recently published series of patients treated at National Jewish Health for MDR-TB, there were a modest number of cases that met the definition of XDR-TB.  While they did not respond as well as the MDR-TB cases, over half were eventually cured (Chan, AJRCCM, 2003).  Resectional surgery -- removal of diseased portions of the lungs -- was a central element of management.

How is National Jewish Health contributing to the fight against TB?
National Jewish Health researchers and clinicians have been fighting tuberculosis since 1899; today, we are battling TB in the following ways:

• Clinical Tuberculosis Laboratory:

The laboratory serves two primary roles: to identify mycobacterium tuberculosis in patient samples, and to test the organism for susceptibility to various drugs.  Because the lab has such an excellent reputation, National Jewish Health also has become a proving ground for new drugs and diagnostic tests.  Researchers use the new tests, analyze the results and provide pharmaceutical companies with valuable feedback on their products.  These advances then become available to patients at National Jewish Health and across the country.  The laboratory is currently researching, through a multi million dollar grant from the National Institutes of Health, an “ultra-short” drug approach for TB patients infected with the AIDS virus or drug-resistant strains of TB. 
Learn more about the Mycobacteriology Laboratory

• Infectious Disease Pharmacokinetics Laboratory (IDPL):

This unique national laboratory helps fine-tune TB treatment by determining the dosage of drugs an individual patient needs to control the disease.  The IDPL does this through comprehensive monitoring and analysis of blood drug levels, an important indicator of the amount of drugs reaching the patient’s disease-infected lungs and other infection sites.  Such monitoring is critical to the treatment of TB patients with HIV and AIDS.  It can determine just how much of the anti-TB drugs are being absorbed into their bloodstreams, allowing physicians to adjust the dosage accordingly.  The IDPL is the only laboratory in the United States capable of conducting many of these tests, and receives approximately 150 patient samples each month from outside National Jewish Health.
Learn more about the Infectious Disease Pharmacokinetics Laboratory

• Drug Assay Development: 

Both the Clinical Tuberculosis Laboratory and the IDPL develop revolutionary new assays for specific drugs.  Assays allow clinicians to accurately test how much of a drug is needed to control the disease, how it will interact with other drugs and how it will be absorbed by the body before it is given to patients.  This is a critical factor in the treatment of TB, which requires potent drug therapy. 

• Mycobacteriology Consult Line: 

Staffed by a highly experienced registered nurse, this free national “hotline” helps physicians manage drug-resistant TB and other mycobacterial infections.  The consultation coordinator teams up with physicians from the Infectious Disease Division at National Jewish Health to respond to about 1,000 calls a year.  This team provides recommendations on appropriate drug therapy, duration of therapy, and, when needed, patient referrals to National Jewish Health.

What is Non-Tuberculous Mycobacteria (NTM)?

National Jewish Health serves as the National Registry for Non-Tuberculous Mycobacterial Disease, TB’s non-contagious, but equally debilitating cousin.  Unlike Mycobacterium tuberculosis, NTM is not transmitted through airborne droplets, but is prevalent in soil and water.  The NTM organism primarily attacks individuals whose respiratory tracts have been weakened by diseases such as chronic bronchitis and emphysema or by chronic exposure to heavy dusts through such occupations as hard rock mining. 

As with TB, the incidence of NTM is on the rise.  Currently, NTM accounts for nearly 10 percent of Mycobacterium infections in the U.S.   Health officials estimate that some 3,000 to 5,000 new cases of NTM occur each year.  While NTM symptoms mimic those of TB, the disease typically does not respond well to anti-TB drugs.
Read more about Non-Tuberculous Mycobacteria (NTM).

For further information:
http://nationaljewish.org
http://www.cdc.gov/tb/
http://www.who.int/tb/en/