Bacteria become active as a result of anything that can reduce the person's immunity, such as HIV, advancing age, diabetes or other immunocompromising illnesses.

TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampicin, pyrazinamide and ethambutol).

[13] Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.

Some mechanisms of drug resistance include:[17] One example is a mutation in the rpoB gene, which encodes the beta subunit of the bacterium's RNA polymerase enzyme.

Mutation in the rpoB gene changes the sequence of amino acids and eventual conformation, or arrangement, of the beta subunit.

Mutations in the katG gene make the enzyme catalase peroxidase unable to convert INH to its biologically active form.

New drugs are being developed to treat extensively resistant forms but major improvements in detection, diagnosis, and treatment will be needed.

They urge that the DOTS protocol be constantly reformed in the context of local practices, forms of knowledge and everyday life.

Denial of treatment remains a difficult human rights issue, as the high cost of second-line medications often precludes those who cannot afford therapy.

This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone).

"[45] Medicines recommended are the following: For patients with RR-TB or MDR-TB, "not previously treated with second-line drugs and in whom resistance to fluoroquinolones and second-line injectable agents was excluded or is considered highly unlikely, a shorter MDR-TB regimen of 9–12 months may be used instead of the longer regimens (conditional recommendation, very low certainty in the evidence).

Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason).

[68] In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option.

[69] These treatments fell out of favor with the invention anti-tuberculosis drugs in the mid-20th century and have not seen a revival with MDR-TB, except for thoracoplasty done with implanted muscle tissue.

[41] TB strains are often less fit and less transmissible, and outbreaks occur more readily in people with weakened immune systems (e.g., patients with HIV).

[77] In 2013, the Mexico–United States border was noted to be "a very hot region for drug resistant TB", though the number of cases remained small.

Several of the less powerful second-line drugs, which are required to treat MDR-TB, are also more toxic, with side effects such as nausea, abdominal pain, and even psychosis.

The Partners in Health team had treated patients in Peru who were sick with strains that were resistant to ten and even twelve drugs.

[82] MDR-TB is widespread in Somalia, where 8.7% of newly discovered TB cases are resistant to Rifampicin and Isoniazid, in patients which were treated previously the share was 47%.

A few number of cases in four different countries were considered by the European Centre for Disease Prevention and Control to pose no risk to the native population.

[85] Baussano et al. articulate that concerning statistics like these are especially worrisome because spikes in TB incidence in prisons are linked to corresponding outbreaks in surrounding communities.

[85] Even as the DOTS program is expanded throughout Russian prisons, researchers such as Shin et al. have noted that wide-scale interventions have not had their desired effect, especially with regard to the spread of drug-resistant strains of TB.

[citation needed] Shin et al. emphasize another factor in MDR-TB prevalence in Russian prisons: alcohol and substance use.

Indeed, of the 80 newly released TB-infected inmates in Fry et al.'s study, 73.8% did not report visiting a community dispensary for further treatment.

[88] Fry et al.'s study also listed side effects of TB treatment medications (especially in HIV positive individuals), financial worries, housing insecurities, family problems, and fear of arrest as factors that prevented some prisoners from properly adhering to TB treatment.

[90] They also note that some researchers have argued that the short-term gains TB-positive prisoners receive, such as better food or work exclusion, may dis-incentivize becoming cured.

[90] In their World Health Organization article, Gelmanova et al. posit that non-adherence to TB treatment indirectly contributes to bacterial resistance.

[84] Russian-based therapy (i.e., not DOTS) has been criticized by Kimerling et al. as "inadequate" in properly controlling TB incidence and transmission.

[88] Because the incidence of MDR-TB is strongly predicted by past imprisonment, the health of Russian society will be greatly impacted by this change.

[89] While second-line drugs necessary for treating MDR-TB are arguably more expensive than a typical regimen of DOTS therapy, infectious disease specialist Paul Farmer posits that the outcome of leaving infected prisoners untreated could cause a massive outbreak of MDR-TB in civilian populations, thereby inflicting a heavy toll on society.