Definitions of MDR-TB and XDR-TB
Multidrug-resistant tuberculosis (MDR-TB) is defined as TB caused by Mycobacterium tuberculosis resistant to at least isoniazid and rifampin, the two most effective first-line TB drugs, while extensively drug-resistant tuberculosis (XDR-TB) is defined as MDR-TB with additional resistance to any fluoroquinolone plus at least one priority A drug (bedaquiline or linezolid). 1
MDR-TB Definition
MDR-TB requires resistance to both isoniazid and rifampin simultaneously. 2 These are the two most powerful first-line anti-TB drugs among the four standard first-line agents (the other two being ethambutol and pyrazinamide). 2
- MDR-TB is difficult to cure, requiring 18-24 months of treatment after sputum culture conversion with a regimen consisting of four to six medications with toxic side effects. 2
- The mortality risk for MDR-TB is greater than that of drug-susceptible TB, with mortality rates typically exceeding 10% (range: 8-21%). 2
- Globally, an estimated 3.7% of persons with newly diagnosed TB and 20% of persons with previously treated TB have MDR-TB. 2
XDR-TB Definition: Updated 2020 Criteria
The definition of XDR-TB was updated in 2020 to reflect current treatment paradigms. 1 The previous definition (pre-2020) defined XDR-TB as MDR-TB with additional resistance to any fluoroquinolone and at least one second-line injectable drug (kanamycin, amikacin, or capreomycin). 2
The current WHO definition (2020 onwards) defines XDR-TB as TB resistant to rifampicin, plus any fluoroquinolone, plus at least one priority A drug (bedaquiline or linezolid). 1
- This updated definition reflects the diminished role of second-line injectable drugs in modern MDR-TB treatment regimens. 3
- Evidence supporting this change showed that resistance to fluoroquinolones significantly increased odds of unfavorable treatment outcomes (adjusted OR 1.91), while administration of bedaquiline and/or linezolid improved outcomes regardless of resistance patterns. 3
- XDR-TB has been reported in 84 countries, with approximately 9% of MDR-TB cases having additional resistance qualifying as XDR-TB. 2, 1
Pre-XDR TB Definition
Pre-extensively drug-resistant TB (pre-XDR TB) is defined as MDR-TB with additional resistance to any fluoroquinolone, but not meeting full XDR-TB criteria. 1 This represents an intermediate category between MDR-TB and XDR-TB. 2
Related Resistance Patterns
Other important resistance patterns to distinguish from MDR-TB and XDR-TB include: 2
- Mono-resistant TB: Resistance to one TB drug only. 2
- Polyresistant TB: Resistance to two or more TB drugs other than both rifampin and isoniazid. 2
- Rifampicin-resistant TB (RR-TB): TB resistant to rifampicin only, which is often treated similarly to MDR-TB. 1
Clinical Implications
The distinction between these definitions has critical treatment implications. 1 MDR-TB generally requires 18-24 months of treatment with second-line drugs, while XDR-TB requires even more complex regimens with at least 5 effective drugs in the intensive phase and 4 drugs in the continuation phase. 1
A common pitfall is failing to recognize that approximately two-thirds of individuals who develop MDR/RR-TB each year are not receiving appropriate treatment globally. 1 Early detection through rapid molecular testing (GeneXpert, whole genome sequencing) is essential for appropriate treatment initiation. 1