Surveillance Definitions for Extensively Drug Resistant (XDR) and Pre-XDR Tuberculosis

At a glance

This letter shares updated CDC definitions for extensively drug-resistant (XDR) and pre-XDR TB per the World Health Organization (WHO) Global TB Programme revisions in 2021.

Dear Colleague Letters

January 18, 2022

Dear Colleague:

Effective with national tuberculosis (TB) products published starting this year (using data on TB cases counted in 2021), CDC is adopting new definitions of extensively drug-resistant (XDR) and pre-XDR TB. This change is the result of the announcement, in January 2021, that the World Health Organization (WHO) Global TB Programme has revised its definition of XDR TB and for the first time formally defined pre-XDR TB.1

The stated reasons for WHO's change in definitions were to "...define more precisely groups of TB patients who require complex treatment regimens," "...lead to better reporting, surveillance and monitoring of drug-resistant TB...," and " ...stimulate the development of better treatment regimens for these dangerous forms of TB disease."

The CDC Division of TB Elimination (DTBE) has studied the new WHO definitions and determined that while the new WHO definitions reflect the direction that drug-resistant TB treatment is evolving, that it would be premature to eliminate second-line injectable drugs (i.e., amikacin, kanamycin, and capreomycin) from the U.S. definitions of pre-XDR and XDR TB at this time.

Accordingly, at this time DTBE is adopting a new hybrid definition of pre-XDR and XDR TB for U.S. TB surveillance purposes that allows for either the existing U.S. definitions or the WHO definitions to be used, with the exception that documented resistance to isoniazid (WHO definitions are inclusive of rifampin resistance only) would be a requirement for all U.S. resistance classifications.

This approach keeps the current U.S. pre-XDR and XDR TB definitions intact but recognizes the revised WHO definitions within the United States and adds bedaquiline and linezolid to the list of drug classes that are considered when classifying cases into resistance groups.

The new U.S. surveillance definitions are shown below:

  • MDR TB: caused by an organism that is resistant to at least isoniazid and rifampin
  • Pre-XDR TB: caused by an organism that is resistant to isoniazid, rifampin, and a fluoroquinolone OR by an organism that is resistant to isoniazid, rifampin, and a second-line injectable (amikacin, capreomycin, and kanamycin)
  • XDR TB: caused by an organism that is resistant to isoniazid, rifampin, a fluoroquinolone, and a second-line injectable (amikacin, capreomycin, and kanamycin) OR by an organism that is resistant to isoniazid, rifampin, a fluoroquinolone, and bedaquiline or linezolid
Resistance classifications and drug classes for MDR, pre-XDR, or XDR TB.
Drug Classes
Resistance classification Isoniazid & Rifampin Fluoroquinolone (at least one) Second-Line Injectable (at least one) Bedaquiline Linezolid
MDR TB X
Pre-XDR* TB X X
X X
XDR* TB X X X
X X X
X X X

* Each row indicates one combination of drug resistance that meets the respective definition of pre¬ XDR or XDR TB.

If you have questions about this change or any other TB surveillance topic, please contact the DTBE Help Desk at 888-300-4261, Service Now or via email at DTBEsupport@cdc.gov.

As always, we appreciate your dedicated efforts towards national TB surveillance. Please do not hesitate to contact us with any questions or concerns.

Sincerely,

Adam J. Langer, DVM, MPH, DACVPM
Chief, Surveillance, Epidemiology, and Outbreak Investigations Branch
Division of Tuberculosis Elimination

Angela M. Starks, Ph.D.
Chief Laboratory Branch
Division of Tuberculosis Elimination