Treatment Failure and Drug-Resistant Tuberculosis

Definition and Diagnostic Criteria

The American Thoracic Society defines treatment failure as persistently positive sputum cultures after 4 months of treatment in patients receiving appropriate chemotherapy with assured medication ingestion 1, 2, 3
Culture positivity after 4 months is the definitive criterion for treatment failure in the United States, while European and WHO guidelines use 5 months as the threshold 1, 4, 5, 6
Patients should show clinical improvement and 90-95% should be culture-negative by 3 months with drug-susceptible TB treated with INH and RIF 1, 2, 7

The American College of Chest Physicians recommends never adding a single drug to a failing regimen, as this leads to rapid development of resistance to that new agent 1, 2, 3, 7, 8, 9
Patients with treatment failure should have at least 2-3 new drugs added to which susceptibility can be logically inferred 2, 7, 9
Isolates should be sent promptly to a reference laboratory for drug susceptibility testing to both first- and second-line agents 2, 7
Consultation with a TB specialist or specialized treatment center is recommended immediately 7, 9

The Centers for Disease Control and Prevention defines MDR-TB as tuberculosis caused by strains of M. tuberculosis resistant to at least isoniazid (INH) and rifampin (RIF) 7, 8, 9
MDR-TB patients require referral to or consultation with specialized treatment centers and treatment guided by drug susceptibility testing 7, 9, 10
Treatment regimens must be individualized based on susceptibility studies, and empirical MDR-TB regimens include a fluoroquinolone, an injectable agent, and an additional oral agent 8
Treatment duration is typically 18-24 months or longer 10