Treatment of MDR-TB requires second-line drugs (i.e., fluoroquinolones, aminoglycosides, and others), which in general are less effective, more toxic and much more expensive than first-line drugs. Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for 2 years, compared to the 6 months of first-line drug treatment, and cost over US$100,000. If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB. Resistant strains of TB are already present in the population, so MDR-TB can be directly transmitted from an infected person to an uninfected person. In this case a previously untreated person develops a new case of MDR-TB. This is known as primary MDR-TB, and is responsible for up to 75% of cases. Acquired MDR-TB develops when a person with a non-resistant strain of TB is treated inadequately, resulting in the development of antibiotic resistance in the TB bacteria infecting them. These people can in turn infect other people with MDR-TB.MDR-TB caused an estimated 600,000 new TB cases and 240,000 deaths in 2016 and MDR-TB accounts for 4.1% of all new TB cases and 19% of previously treated cases worldwide. Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.Treatment of MDR-TB requires treatment with second-line drugs, usually four or more anti-TB drugs for a minimum of 6 months, and possibly extending for 18–24 months if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected.
Medicines recommended are the following:

Group A: Fluoroquinolones (levofloxacin,moxifloxicin), linezolid, bedaquiline
Group B: clofazimine, cycloserine/terizidone
Group C: Other core second-line agents (ethambutol, delamanid, pyrazinamide, imipenem-cilastatin/meropenem, amikacin/streptomycin, ethionamide/prothionamide, p-aminosalicylic acid)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). "In general, resistance to one drug within a class means resistance to all drugs within that class, but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-resistance, and the laboratory should be asked to test for it. It is possible to use only one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high-level INH-resistance be looked for. If the strain has only low-level INH-resistance (resistance at 0.2 mg/L INH, but sensitive at 1.0 mg/L INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter).