Treatment of Drug-Resistant Tuberculosis
||Treatment of Drug-Resistant Tuberculosis
Last Updated: July 2007
Drug-resistant tuberculosis (TB) is TB disease caused by M. tuberculosis
organisms 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).
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.
Drug resistance is proven by drug-susceptibility testing. However,
since this testing can take weeks, treatment should be started with
an empirical treatment regimen based on expert advice as soon as
drug-resistant TB disease is suspected. When the testing results
are known, the treatment regimen should be adjusted according to
the results. Patients should be monitored closely throughout treatment.
Directly observed therapy (DOT) always should be used in the treatment
of drug-resistant TB to ensure adherence.
Although the treatment of drug-resistant TB in persons with HIV
infection is the same as for patients without HIV (see Table 1),
management of HIV-related TB requires expertise in the management
of both HIV and TB. Providers must monitor the interactions among
many of the antiretroviral drugs. RIF should not be used with most
antiretroviral drugs. Rifabutin, which has fewer problematic drug
interactions, may be used in place of RIF. As new antiretroviral
agents and pharmacokinetic data become available, these recommendations
are likely to be modified. Visit http://www.cdc.gov/tb/tb_hiv_drugs/default.htm
for the most recent recommendations.
Treatment for children who have TB disease after exposure to a drug-resistant
case should be guided by the source-case susceptibility results.
When a source is unknown and circumstances suggest an increased
risk of drug resistance, children should be treated with a standard
four-drug initial-phase regimen until their susceptibility pattern
is known. Ethambutol (EMB) can be used safely (15-20 mg/kg per day),
in the likelihood of INH resistance. Streptomycin, kanamycin, or
amikacin also can be selected as the fourth drug. Long-term use
of fluoroquinolones in children has not been approved. However,
most experts agree that these drugs should be considered for children
with MDR TB. Consultation with a specialist in pediatric TB treatment
Case management for pregnant women who have drug-resistant TB requires
consultation with an expert because most second-line drugs can have
harmful effects on the fetus. Pyrazinamide (PZA) should not be used
as part of the treatment regimen for pregnant women. Counseling
concerning risks to the fetus should be provided.
Close Contacts of Drug-Resistant TB Patients
Contacts of isoniazid-resistant TB. For persons who have
been exposed to INH-resistant, RIF-susceptible TB and are known
or suspected to have latent TB infection (LTBI), a 4-month regimen
of daily RIF is recommended. When RIF cannot be used, rifabutin
may be substituted.
Contacts of MDR TB. For persons with known or suspected
LTBI resistant to both INH and RIF, alternative regimens should
be considered. Alternative regimens should include two drugs to
which the TB strain is susceptibile. A potential regimen should
include a daily fluoroquinolone. Contacts who are not immunosuppressed
may be treated for 6 months or observed without treatment. All persons
with suspected MDR LTBI should be monitored for 2 years regardless
of the treatment regimen.
For More Information
American Thoracic Society, Centers for Disease Control and Prevention,
and Infectious Diseases Society of America. Treatment
of tuberculosis. MMWR 2003; 52 (No. RR-11).
American Thoracic Society and Centers for Disease Control and
tuberculin testing and treatment of latent TB infection. MMWR
2000; 49 (No. RR-6).
American Thoracic Society and Centers for Disease Control and Prevention.
Adverse event data and revised American Thoracic Society/CDC recommendations
against the use of rifampin and pyrazinamide for treatment of latent
tuberculosis infection. MMWR 2003; 52 (No. 31)
Centers for Disease Control and Prevention. Updated
guidelines for the use of rifamycins for the treatment of tuberculosis
among HIV-infected patients taking protease inhibitors or nonnucleoside
reverse transcriptase inhibitors. MMWR 2004; 53 (No.