Fact Sheets
Treatment of Drug-Resistant Tuberculosis
Last Updated: November 24, 2003
Summary
Multidrug-resistant TB (MDR TB), particularly among HIV-infected
persons, contributed to the resurgence of TB in the late 1980s and
early 1990s. Resistance to anti-TB drugs among reported TB cases
in the United States remains a serious public health concern. Since
CDC began monitoring anti-TB drug resistance through the national
TB surveillance system in 1993, levels of isoniazid resistance have
been relatively stable. Overall, the number and proportion of MDR
TB cases has decreased. Nevertheless, during 1993-1998, 45 states
and the District of Columbia reported cases of multidrug-resistant
TB. The extent of drug resistance confirms the importance of initial
treatment regimens of four first-line drugs for most TB patients
and the use of drug susceptibility testing to guide optimal treatment
of patients with culture-positive disease. All health departments
must be prepared to deal with the challenge of MDR TB, which includes
the capacity to ensure that clinicians with expertise in the management
of MDR TB are always involved in the care of these patients.
Treatment of latent TB infection
Contacts of isoniazid-resistant TB. For persons who are
known to be contacts of patients with isoniazid-resistant, rifampin-susceptible
TB, a 4-month regimen of daily rifampin is recommended. In situations
where rifampin cannot be used, rifabutin may be substituted.
Contacts of multidrug-resistant TB. For persons
likely to have been infected with a strain of M. tuberculosis
resistant to both isoniazid and rifampin, alternative regimens should
be considered. Alternative regimens should consist of two drugs
to which the infecting organism has demonstrated susceptibility.
Potential alternative regimens include either 6-12 months of daily
ethambutol and pyrazinamide or 6-12 months of pyrazinamide and a
quinolone (i.e, levofloxacin, ofloxacin, or ciprofloxacin). Immunocompetent
contacts may be treated for 6 months or observed without treatment.
Immunocompromised contacts (e.g., HIV-positive persons) should be
treated for 12 months. Persons receiving pyrazinamide and a quinolone
antibiotic should be monitored closely for adverse effects. Some
evidence suggests that the combination of pyrazinamide and ofloxacin
may be poorly tolerated. All persons with suspected multidrug-resistant
LTBI should be followed for 2 years regardless of the treatment
regimen.
Ethambutol at the usual dose is safe for children. The regimen
of pyrazinamide and ethambutol for 9-12 months is recommended for
children if the infecting organism has demonstrated susceptibility.
When pyrazinamide and/or ethambutol cannot be used, a combination
of two other drugs to which the infecting organism is likely susceptible
is recommended.
Treatment of drug-resistant TB disease
Clinicians who are unfamiliar with the treatment of drug-resistant
TB should seek expert consultation. Because second-line drugs can
cause serious adverse reactions, patients taking these drugs should
be monitored closely throughout the course of treatment. The role
of agents such as the quinolone derivatives and amikacin in the
treatment of multidrug-resistant disease is not well characterized,
although these drugs are commonly being used in such cases. Surgery
seems to offer considerable benefit and a significantly improved
cure rate for patients who have multidrug-resistant TB if the bulk
of disease can be resected. However, drug therapy is usually required
to sterilize the remaining disease.
TB disease resistant to isoniazid only. A 6-month regimen
of isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin
has been demonstrated to be effective for the treatment of TB resistant
only to isoniazid. When resistance to isoniazid is documented during
the recommended initial four-drug therapy, the regimen should be
adjusted by discontinuing isoniazid and continuing the other three
drugs for the entire 6 months of therapy. TB resistant only to isoniazid
may also be treated with rifampin and ethambutol for 12 months.
When isoniazid resistance is documented in the 9-month regimen
without pyrazinamide, isoniazid should be discontinued. If ethambutol
was included in the initial regimen, treatment with rifampin and
ethambutol should be continued for a minimum of 12 months. If ethambutol
was not included initially, susceptibility tests should be repeated,
isoniazid should be discontinued, and two drugs (e.g., ethambutol
and streptomycin) should be added. The regimen can be adjusted when
the results of the susceptibility tests become available.
Multidrug-resistant TB (resistant to both isoniazid and rifampin).
Multidrug-resistant TB (i.e., TB resistant to at least isoniazid
and rifampin) presents difficult treatment problems. Treatment must
be individualized and based on the patient's medication history
and susceptibility studies.
Unfortunately, adequate data are not available on the effectiveness
of various regimens and the necessary duration of treatment for
patients with organisms resistant to both isoniazid and rifampin.
Moreover, many of these patients also have resistance to other first-line
drugs (e.g., ethambutol and streptomycin) when drug resistance is
discovered. Because of the poor outcome in such cases, it is preferable
to give at least three new drugs to which the organism is susceptible.
This regimen should be continued until culture conversion is documented,
followed by at least 12 months of two-drug therapy. Often, a total
of 24 months of therapy is given empirically. Some experts recommend
that at least 18-24 months of three-drug therapy be given after
culture conversion.
TB Treatment for HIV-Infected Patients with Drug-Resistant
TB Disease
TB disease resistant to isoniazid only. The treatment regimen
should generally consist of a rifamycin (rifampin or rifabutin),
pyrazinamide, and ethambutol for the duration of treatment. Because
the development of acquired rifamycin resistance would result in
MDR TB, clinicians should carefully supervise and manage TB treatment
for these patients.
TB disease resistant to rifampin only. The 9-month treatment
regimen should generally consist of an initial 2-month phase of
isoniazid, streptomycin, pyrazinamide, and ethambutol. The second
phase of treatment should consist of isoniazid, streptomycin, and
pyrazinamide administered for 7 months. Because the development
of acquired isoniazid resistance would result in MDR TB, clinicians
should carefully supervise and manage TB treatment for these patients.
Multidrug-resistant TB (resistant to both isoniazid and rifampin).
These patients should be managed by or in consultation with physicians
experienced in the management of MDR TB. Most drug regimens currently
used to treat MDR TB include an aminoglycoside (e.g., streptomycin,
kanamycin, amikacin) or capreomycin, and a fluoroquinolone. The
recommended duration of treatment for MDR TB in HIV-seropositive
patients is 24 months after culture conversion, and posttreatment
follow-up visits to monitor for TB relapse should be conducted every
4 months for 24 months. Because of the serious personal and public
health concerns associated with MDR TB, health departments should
always use directly observed therapy (DOT) for these patients and
take whatever steps are needed to ensure their adherence to the
treatment regimen.
For More Information
For information about implementing CDC guidelines,
call your state health department.
To order the following documents, call the CDCs
Voice and Fax Information System (recording) toll free at (888)
232-3228, then press options 2, 5, 1, 2, 2 (Note: You may select
these options at any time without listening to the complete message).
Request the title or publication number of the document you would
like to order. You may also visit the Division of TB Eliminations
Web site at http://www.cdc.gov/nchstp/tb.
Publication # 99-6422. ATS/CDC. Targeted tuberculin testing and
treatment of latent TB infection. MMWR
2000;49(No. RR- 6).
Publication # 99-5879. CDC. Prevention and treatment
of tuberculosis among patients infected with human immunodeficiency
virus: principles of therapy and revised recommendations. MMWR
1998;47(No. RR- 20).
Publication # 00-6453. ATS/CDC. Treatment
of tuberculosis and tuberculosis infection. Am J Respir
Crit Care Med 1994;149.
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