What is the definition of Extensively Drug-Resistant Tuberculosis (XDR TB)?

Definition of Extensively Drug-Resistant Tuberculosis (XDR TB)

Extensively Drug-Resistant Tuberculosis (XDR TB) is defined as tuberculosis that is resistant to rifampicin, plus any fluoroquinolone, plus at least one further priority A drug (bedaquiline or linezolid). 1

Evolution of the XDR TB Definition

The definition of XDR TB has evolved over time based on treatment approaches and understanding of drug resistance patterns:

• Previous Definition (before 2020): XDR TB was defined as MDR TB (resistance to at least isoniazid and rifampicin) with additional resistance to any fluoroquinolone and at least one of three injectable second-line TB drugs (i.e., amikacin, kanamycin, or capreomycin). 2

• Current Definition (2022): The World Health Organization now classifies XDR TB as TB resistant to rifampicin, plus any fluoroquinolone, plus at least one further priority A drug (bedaquiline or linezolid). 1

Classification of Drug-Resistant TB

The WHO classifies drug-resistant TB into 5 categories:

1. Isoniazid-resistant TB: Resistance to isoniazid only
2. Rifampicin resistant (RR)-TB: Resistance to rifampicin only
3. MDR-TB: TB resistant to both isoniazid and rifampicin
4. Pre-XDR TB: MDR-TB with resistance to a fluoroquinolone
5. XDR-TB: TB resistant to rifampicin, plus any fluoroquinolone, plus at least one priority A drug (bedaquiline or linezolid) 1

Clinical Significance of XDR TB

XDR TB represents a significant clinical challenge:

• Treatment Difficulty: XDR TB is more difficult to treat than other forms of TB, with treatment success rates generally between 30-50% 2
• Treatment Duration: Treatment typically requires at least 18-24 months of four to six second-line anti-TB drugs 2
• Mortality Risk: XDR TB carries a greater mortality risk compared to drug-susceptible TB, with mortality rates exceeding 10% 1
• Outcomes: Particularly poor outcomes are seen in HIV-infected patients 2

Epidemiology

• As of 2020, XDR TB has been reported in 84 countries worldwide 1
• Approximately 9% of MDR TB cases have additional resistance qualifying as XDR TB 1
• In 2020, there were 25,681 cases of pre-XDR-TB or XDR-TB detected globally 1

Diagnostic Considerations

Diagnosis of XDR TB requires:

• Bacteriological confirmation of TB
• Drug susceptibility testing showing resistance to rifampicin, any fluoroquinolone, and at least one priority A drug (bedaquiline or linezolid)
• Conventional culture-based methods typically take several weeks, though molecular testing methods are improving 2

Treatment Implications

The definition change reflects the evolution in treatment approaches:

• Injectable agents are now less emphasized in MDR TB treatment regimens
• Newer drugs like bedaquiline and linezolid have become increasingly important in treatment regimens
• Resistance to these priority A drugs significantly impacts treatment options and outcomes 3

The updated definition of XDR TB aligns with current treatment recommendations and helps guide appropriate therapy selection for these challenging cases.