XDR‑TB (extensively drug‑resistant tuberculosis) describes strains of *Mycobacterium tuberculosis* that are resistant to isoniazid and rifampicin, plus any fluoroquinolone and at least one second‑line injectable agent. These strains emerge from multidrug‑resistant tuberculosis under selection pressure from inadequate or incomplete treatment.
Resistance mechanisms and epidemiology
Resistance to first‑ and second‑line antituberculosis drugs arises through chromosomal mutations in genes encoding drug targets or activating enzymes. Mutations in *katG* and *inhA* confer resistance to isoniazid, while alterations in *rpoB* are responsible for rifampicin resistance. Fluoroquinolone resistance often involves mutations in the *gyrA* or *gyrB* genes, and resistance to injectable agents such as amikacin and capreomycin can involve mutations in the 16S rRNA gene (*rrs*) or promoter regions. XDR‑TB has been documented on all continents but is most prevalent in regions with high tuberculosis burden and weak treatment programs, including parts of South Africa, eastern Europe and Asia. Diagnosis requires culture and drug‑susceptibility testing or molecular assays capable of detecting resistance mutations, and rapid identification is critical for infection control and appropriate therapy.
Clinical implications and notable cases
Patients with XDR‑TB often have previous treatment histories and prolonged infectious periods, posing a significant risk to contacts and healthcare workers. Treatment options are limited, toxic, and prolonged, combining second‑line drugs such as linezolid, bedaquiline, delamanid, clofazimine and cycloserine. Cure rates are considerably lower than for drug‑susceptible TB, and mortality can exceed 50%. A well‑known outbreak occurred in Tugela Ferry, South Africa, in 2005‑2006, where an HIV co‑infected cohort experienced rapid fatal disease; this outbreak drew global attention to XDR‑TB and spurred efforts to strengthen laboratory surveillance and develop new therapeutics. Infection control measures such as isolation, proper ventilation and respiratory protection are essential to prevent nosocomial transmission. Extensively drug‑resistant tuberculosis represents the most severe end of the drug‑resistant TB spectrum, combining resistance to core first‑line agents with key second‑line drugs. Its emergence underscores the importance of supervised, complete treatment of tuberculosis and investment in diagnostic capacity and new medications. Related Terms: Mycobacterium tuberculosis, MDR‑TB, Fluoroquinolone, Drug resistance, WHO