The only definitive way of diagnosing drug resistance is by isolating M. tuberculosis from the sputum/tissue and assessing its susceptibility pattern, which takes up to 12 weeks.

Child contacts of adults with drug resistant TB should be treated according to the drug susceptibility patterns of the M. tuberculosis strain of the source cases unless their own strain's susceptibility testing indicates otherwise. Contact tracing remains of fundamental importance in identifying children at risk.

Therapy for drug resistant TB is successful when at least 2 bactericidal drugs to which the infecting strain of M. tuberculosis is susceptible are given. Exact treatment regimens can be individually tailored to the specific pattern of drug resistance. If this is not available, at least 3 drugs to which the patient is not exposed earlier should be given. Resistance to INH or Streptomycin alone can be managed with standard 4-drug regimen with good results. However when resistance to both INH and Rifampicin is present (MDR-TB), the management is more complicated and requires second line drugs (e.g. Ofloxacin, Ethionamide, aminoglycoside). A standard regimen used is S3 / Ofloxacin, Ethambutol, Ethionamide, Pyrazinamide. The duration of therapy is usually 18-24 months with an injectable drug for the 1st 6 months. Occasionally, surgical resection of the diseased lung or lobe is required.