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National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

Division of Tuberculosis Elimination

TB Elimination

Treatment of Drug-Resistant Tuberculosis

Introduction

Drug-resistant tuberculosis (TB) is TB disease 

caused by Mycobacterium tuberculosis (M.tb.) 

organisms that are resistant to at least one firstline anti-TB drug. Multidrug-resistant TB (MDR 

TB) is caused by an organism that is resistant to 

at least isoniazid (INH) and rifampin (RIF), the 

two most potent TB drugs. 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 diagnosed by drugsusceptibility testing in the laboratory. However, 

since these tests can take several weeks, treatment 

could be started with an empirical treatment 

regimen based on expert advice, depending on 

the probability that the person has drug-resistant 

TB disease. When 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) should always be used 

in the treatment of drug-resistant TB to ensure 

adherence.

Special Considerations

People infected with HIV

Although the treatment of drug-resistant TB in 

persons with HIV infection is similar to patients 

without HIV (see Table 1) (http://www.cdc.gov/tb/

publications/guidelines/TB_HIV_Drugs/Table1.

htm), 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 Managing Drug Interactions 

in the Treatment of HIV-Related Tuberculosis

(http://www.cdc.gov/tb/publications/guidelines/

TB_HIV_Drugs/default.htm) for the most recent 

recommendations.

Children

In cases of suspected drug-resistant TB in a 

child, specimens for microbiological evaluation 

should be obtained. For pulmonary disease, 

if the child is too young to provide adequate 

sputum specimens, nasogastric lavage or 

bronchoscopy should be considered. For pleural 

disease, thoracentesis with pleural biopsy may be 

considered. For extrapulmonary disease, needle 

aspiration or biopsy of the affected tissue can 

provide a microbiological diagnosis. In addition 

to microscopy, culture, and drug susceptibility 

tests, some of the newer molecular methods 

may be able to detect M.tb. DNA as well as DNA 

mutations associated with drug resistance. Initial 

treatment for children with suspected drugresistant TB disease (e.g., after exposure to a 

person with drug-resistant TB) should be guided 

by the source-case susceptibility results until the 

drug susceptibility results for the child’s isolate 

are available. If an isolate from the child under 

treatment is not available, drug susceptibilities 

can be inferred by the drug susceptibility pattern 

of isolates from the adult source case. 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 with close clinical monitoring, until 

their susceptibility pattern is known and then 

the regimen should be adjusted accordingly. As 

in adults, treating and curing drug-resistant TB 

is complicated; all children with suspected or 
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confirmed drug-resistant TB should be managed 

in consultation with an expert. For more

information on TB in Children, please visit the 

TB in Children Web page (http://www.cdc.gov/tb/

topic/populations/TBinChildren/default.htm).

Pregnant Women

Case management for pregnant women who have 

drug-resistant TB requires consultation with an 

expert because most second-line anti-TB drugs 

have unknown effects on the fetus. In most cases, 

pyrazinamide (PZA) is not recommended as part 

of the treatment regimen for pregnant women. 

Counseling concerning risks to the fetus should be 

provided. To learn more about TB and pregnancy, 

please visit the Tuberculosis and Pregnancy

(http://www.cdc.gov/tb/publications/factsheets/

specpop/pregnancy.htm) Web page. 

Close Contacts of Drug-Resistant 

TB Patients

Contacts of isoniazid-resistant TB. For persons 

who have been exposed to INH-resistant, RIFsusceptible TB disease and who 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 resulting from contact with 

a source case who had TB disease resistant to 

both INH and RIF, alternative regimens should be 

considered. Alternative regimens should include 

two drugs to which the TB strain is susceptible. 

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

1. American Thoracic Society, Centers for Disease 

Control and Prevention, and Infectious 

Diseases Society of America. Treatment 

of tuberculosis. MMWR 2003; 52 (No. RR11). http://www.cdc.gov/mmwr/preview/

mmwrhtml/rr5211a1.htm

2. American Thoracic Society and Centers for 

Disease Control and Prevention. Targeted 

tuberculin testing and treatment of latent TB 

infection. MMWR 2000; 49 (No. RR-6). http://

www.cdc.gov/mmwr/preview/mmwrhtml/

rr4906a1.htm

3. American Thoracic Society and Centers for 

Disease Control and Prevention. Update: 

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). http://www.cdc.gov/

mmwr/preview/mmwrhtml/mm5231a4.htm

4. Centers for Disease Control and Prevention. 

Updated guidelines for the use of rifamycins 

for the treatment of tuberculosis among HIVinfected patients taking protease inhibitors or 

nonnucleoside reverse transcriptase inhibitors. 

MMWR 2004; 53 (No. 2). http://www.cdc.gov/

mmwr/preview/mmwrhtml/mm5302a6.htm

5. Francis J. Curry National Tuberculosis Center 

and California Department of Public Health, 

2008: Drug-Resistant Tuberculosis: A Survival 

Guide for Clinicians, 2nd ed. (http://www.

currytbcenter.ucsf.edu/drtb/)

http://www.cdc.gov/tb