The purpose of this study is to assess the efficacy, safety and tolerability of a combination of levofloxacin, linezolid, cycloserine and pyrazinamide (or clofazimine if resistant to pyrazinamide) treatments for 24 to 32 weeks (regimen consisted of clofazimine for 36~44 weeks) in subjects with multidrug-resistant tuberculosis (MDR-TB) compared to WHO standardized shorter regimen of 36-44 weeks.

The TB-TRUST is a phaseIII, multicenter, open-label, randomized controlled trial. The purpose of this study is to assess the feasibility of the ultra-short treatment regimen of all-oral anti-TB drugs among selected MDR-TB patients who are susceptible to fluoroquinolones.

A total of 354 participants with MDR-TB will be recruited and followed up until 84 weeks after randomization. During randomization, eligible patients will be assigned to in a 1:1 ratio to one of the following groups: The WHO standardized shorter regimen group and a PZA sensitivity guided ultra-short regimen group.

WHO standardized shorter regimen group consists of 36-44 weeks with two phases of treatment. The first is an intensive phase of 16 weeks (extended up a maximum of 20 or 24 weeks in case of lack of smear conversion at the end of 16 or 20 weeks), and included moxifloxacin, amikacin, prothionamide, pyrazinamide, high-dose isoniazid, ethambutol, and clofazimine. This is followed by a continuation phase of 20 weeks with the following agents: moxifloxacin, pyrazinamide, ethambutol, and clofazimine.

The PZA sensitivity guided ultra-short regimen consists of two periods of 24-36 weeks. During the first 4-8 weeks (waiting for pyrazinamide drug sensitivity test), the regimen consists of levofloxacin, linezolid, cycloserine, pyrazinamide, and clofazimine. Then based on molecular PZA drug sensitivity results, patients will be in divided into two sub-groups: pyrazinamide-susceptible (PZA-S) patients and pyrazinamide-resistant (PZA-R) patients. The Regimen for PZA-S patients, consisting of levofloxacin, linezolid, cycloserine, and pyrazinamide, are given until the 24th week (prolonged to 28 or 32 weeks if no smear conversion by end of 16th and 20th week). PZA-R sub-group regimen, consisting of levofloxacin, linezolid, cycloserine, and clofazimine given until 36th week (prolonged to 40 or 44 weeks if no smear conversion by end of 16th and 20th week)

The primary objective is to compare the treatment success rate without relapse between the WHO standardized shorter regimen group and the PZA sensitivity guided ultra-short regimen group.

The secondary objective is to compare the median time to sputum culture conversion. Safety evaluations performed are the routine lab tests, blood glucose, hearing, vital signs, electrocardiograph (ECG), reporting of adverse events, peripheral neuropathy brief examining with the use of a Brief Peripheral Neuropathy rating scale(BPNS) and ophthalmologic examination, including assessment of visual acuity and color vision，physical examinations and chest CT. Adverse events will be monitored and promptly managed during the whole treatment course.

Inclusion Criteria:

1.Willing to participate in trial treatment and follow-up and can give informed consent 2.18-70 years old 3.Has smear-positive pulmonary tuberculosis with initial laboratory results with resistance to rifampicin confirmed by GeneXpert 4.Willing to carry out HIV testing. 5. If you are a non-menopausal woman, agree to use or have used effective contraception during treatment.

6. Have an identifiable address and stay in the area during the study period. 7.Willing to follow the follow-up study procedure after the follow-up.

Exclusion Criteria:

1. Molecular drug resistance test for infected strains resistant to second-line injection;
2. Molecular drug resistance assay for infected strains resistant to fluoroquinolone;
3. Combined extrapulmonary tuberculosis;
4. HIV antibody positive and AIDS patients;
5. Critically ill patients, and according to the judgment of the research physician, it is impossible to survive for more than 16 weeks;
6. Known to be pregnant or breastfeeding;
7. Unable to attend or follow treatment or follow-up time;
8. Can not take oral medications;
9. Patients with impaired liver function (hepatic encephalopathy, ascites; total bilirubin is more than 2 times higher than the upper limit of normal; ALT or AST is more than 5 times the upper limit of normal);
10. Blood muscle spasm is more than 1.5 times the upper limit of normal;
11. The investigator believes that there are any social or medical conditions that expose the subject to a safety hazard;
12. Simultaneously apply the drugs (glucocorticoids, interferons) that affect the efficacy of this study; and apply the following drugs contraindicated with the study drug, including non-steroidal anti-inflammatory drugs, monoamine oxidase inhibitors (phenethyl hydrazine, different Carbofurs et al), direct or indirect sympathomimetic drugs (such as pseudoephedrine), vasopressor drugs (such as adrenaline, norepinephrine), dopamine drugs (such as dopamine, dobutamine), 5 a serotonin reuptake inhibitor, a tricyclic antidepressant, a serotonin 5-HTI receptor antagonist (amitriptyline), meperidine or buspirone.
13. Being allergic or intolerant of any study drug;
14. Currently participating in another drug clinical trial;
15. QTc interval ≥ 500 milliseconds during screening;
16. Hemoglobin is less than 90g/L or platelet is less than 75*10^9/L;
17. Have epilepsy, severe depression, irritability or psychosis；
18. Alchol abuse（drinking more than 64g of ethanol a day for male, 42g for female）.