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Q and A Related to CDC July 3, 2007 Press Conference with
National Jewish Medical and Research Center
This is an archived document. The links
and content are no longer being updated.
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.
Last Reviewed: 05/18/2008 Content Source: Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
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