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News From the Centers for Disease Control and Prevention
December 20, 2006

Notice to Readers: Revised Definition of Extensively Drug-Resistant Tuberculosis

JAMA. 2006;296(23):2792. doi:10.1001/jama.296.23.2792-a

MMWR. 2006;55:1176

In a report published on March 24, 2006, MMWR reported that CDC, in collaboration with the World Health Organization (WHO) and participating supranational reference laboratories, had agreed to define extensively drug-resistant tuberculosis (XDR TB) as cases of TB disease in persons whose Mycobacterium tuberculosis isolates were resistant to isoniazid and rifampin and at least three of the six main classes of second-line drugs (aminoglycosides, polypeptides, fluoroquinolones, thioamides, cycloserine, and para-aminosalicyclic acid).1 Since that original publication, additional reports have documented the presence of XDR TB in Iran and South Africa with high mortality among persons infected with human immunodeficiency virus (HIV) who are benefiting from antiretroviral therapy.2,3

The emergence and transmission of these strains of M. tuberculosis highlight the urgency of strengthening national TB and HIV/acquired immunodeficiency syndrome control programs worldwide, particularly in settings with high HIV prevalence. CDC is collaborating with national and international health agencies to provide leadership, technical support, and capacity building to ensure proper action is taken to limit the development and spread of XDR TB. An initial consultation was convened by the South Africa Medical Research Council in Johannesburg, South Africa, during September 6-7, 2006. A seven-point emergency action plan to combat XDR TB was issued by agencies represented at this meeting (additional information is available at http://www.mrc.ac.za/pressreleases/8pres2006.htm). Subsequently, WHO organized the first meeting of the Global XDR TB Task Force, held in Geneva, Switzerland, during October 8-9, 2006. This meeting was called by WHO to develop a rapid response to the emerging problem of XDR TB. As a result of the meeting, participants agreed upon a revised case definition of XDR TB. According to laboratory professionals in attendance, drug-susceptibility testing to fluoroquinolones and second-line injectable drugs (i.e., amikacin [aminoglycoside], kanamycin [aminoglycoside], or capreomycin [polypeptide]) yields reproducible and reliable results, whereas drug-susceptibility testing to other second-line drugs is less reliable. Additionally, investigators have observed that resistance to these drugs (fluoroquinolones and second-line injectable drugs) has been associated with poor treatment outcomes. Accordingly, the new agreed-upon definition of XDR TB is the occurrence of TB in persons whose M. tuberculosis isolates are 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).

Health-care providers and local health departments in the United States should collect all second-line drug-susceptibility results obtained at diagnosis and during treatment of persons with TB disease and report these results to their local and state health department TB programs. Complete capture of these results will allow health departments and CDC to accurately identify XDR TB cases and monitor trends. Additional information about XDR TB is available at http://www.who.int/tb/en.

CDC.  Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000-2004.  MMWR. 2006;55:301-305Google Scholar
Masjedi MR, Farnia P, Sorooch S.  et al.  Extensively drug-resistant tuberculosis: 2 years of surveillance in Iran.  Clin Infect Dis. 2006;43:841-84716941364Google ScholarCrossref
Gandhi NR, Moll A, Sturm AW.  et al.  Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa.  Lancet2006;(October):26 http://www.thelancet.com/journals/lancet/article/PIIS0140673606695731. Online16815371Google Scholar