Please review the following recent publications:

Zumla AI1, Gillespie SH2, Hoelscher M3, Philips PP4, Cole ST5, Abubakar I4, McHugh TD6, Schito M7, Maeurer M8, Nunn AJ4. New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects.Lancet Infect Dis. 2014 Apr;14(4):327-40.

Abstract

About 1·3 million people died of tuberculosis in 2012, despite availability of effective drug treatment. Barriers to improvements in outcomes include long treatment duration (resulting in poor patient adherence and loss of patients to follow-up), complex regimens that involve expensive and toxic drugs, toxic effects when given with antiretroviral therapy, and multidrug resistance. After 50 years of no antituberculosis drug development, a promising pipeline is emerging through the repurposing of old drugs, re-engineering of existing antibacterial compounds, and discovery of new compounds. A range of novel antituberculosis drugs are in preclinical development, several phase 2 and 3 trials are underway, and use of adjunct therapies is being explored for drug-sensitive and drug-resistant tuberculosis. Historical advances include approval of two new drugs, delamanid and bedaquiline. Combinations of new and existing drugs are being assessed to shorten the duration of therapy and to treat multidrug-resistant tuberculosis. There has also been progress in development of new antituberculosis drugs that are active against dormant or persister populations of Mycobacterium tuberculosis. In this Review, we discuss recent advances in antituberculosis drug discovery and development, clinical trial designs, laboratory methods, and adjunct host-directed therapies, and we provide an update of phase 3 trials of various fluoroquinolones (RIFAQUIN, NIRT, OFLOTUB, and REMoxTB). We also emphasise the need to engage the community in design, implementation, and uptake of research, to increase international cooperation between drug developers and health-care providers adopting new regimens.

Tasneen R1, Williams K1, Amoabeng O1, Minkowski A1, Mdluli KE2, Upton AM2, Nuermberger EL3. Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis.  Antimicrob Agents Chemother. 2015 Jan;59(1):129-35.

Abstract

New regimens based on two or more novel agents are sought in order to shorten or simplify the treatment of both drug-susceptible and drug-resistant forms of tuberculosis. PA-824 is a nitroimidazo-oxazine now in phase II trials and has shown significant early bactericidal activity alone and in combination with the newly approved agent bedaquiline or with pyrazinamide with or without moxifloxacin. While the development of PA-824 continues, a potential next-generation derivative, TBA-354, has been discovered to have in vitro potency superior to that of PA-824 and greater metabolic stability than that of the other nitroimidazole derivative in clinical development, delamanid. In the present study, we compared the activities of PA-824 and TBA-354 as monotherapies in murine models of the initial intensive and continuation phases of treatment, as well as in combination with bedaquiline plus pyrazinamide, sutezolid, and/or clofazimine. The monotherapy studies demonstrated that TBA-354 is 5 to 10 times more potent than PA-824, but selected mutants are cross-resistant to PA-824 and delamanid. The combination studies revealed that TBA-354 is 2 to 4 times more potent than PA-824 when combined with bedaquiline, and when administered at a dose equivalent to that of PA-824, TBA-354 demonstrated superior sterilizing efficacy. Perhaps most importantly, the addition of either nitroimidazole significantly improved the sterilizing activities of bedaquiline and sutezolid, with or without pyrazinamide, confirming the value of each agent in this potentially universally active short-course regimen.

Bedaquiline for multidrug-resistant tuberculosis.Drug Ther Bull. 2014 Nov;52(11):129-32. doi: 10.1136/dtb.2014.11.0291.

Abstract

Resistance to drugs used to treat tuberculosis (TB) is a major public health problem that threatens progress made in TB management and control worldwide. It may result from improper use of antibiotics, including prescription of non-standard treatment regimens and poor adherence to drug therapy. Multidrug-resistant TB (MDR-TB) is defined as resistance to isoniazid and rifampicin, with or without resistance to other first-line drugs. Extensively drug-resistant TB (XDR-TB) refers to resistance to at least isoniazid and rifampicin, and to any fluoroquinolone, and to any of the three second-line injectables  (amikacin, capreomycin and kanamycin). In 2012, DTB discussed the investigation, management and treatment of patients with MDR- and XDR-TB. Earlier this year, ▼bedaquiline (Sirturo) and ▼delamanid (Deltyba) were authorised by the European Medicines Agency (EMA) under its 'conditional market authorisation' scheme for use as part of an appropriate combination regimen for pulmonary MDR-TB in adult patients "when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability." In this article, we review the evidence for bedaquiline in the management of MDR-TB.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Agree with above, plaease take a look at CDC provisional guidlines

Bedaquiline should be used with clinical expert consultation as part of combination therapy (minimum four-drug treatment regimen) and administered by direct observation to adults aged ≥18 years with a diagnosis of pulmonary MDR TB (Food and Drug Administration. SIRTURO [bedaquiline] tablets label. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf ). Use of the drug also can be considered for individual patients in other categories (e.g., persons with extrapulmonary TB, children, pregnant women, or persons with HIV or other comorbid conditions) when treatment options are limited. However, further study is required before routine use of bedaquiline can be recommended in these populations.

A registry for persons treated with bedaquiline is being implemented by Janssen Therapeutics to track patient outcomes, adverse reactions, laboratory testing results (e.g., diagnosis, drug susceptibility, and development of drug resistance), use of concomitant medications, and presence of other comorbid conditions. Suspected adverse reactions (i.e., any adverse event for which there is a reasonable possibility that the drug caused the adverse event) and serious adverse events (i.e., any adverse event that results in an outcome such as death, hospitalization, permanent disability, or a life-threatening situation) should be reported to Janssen Therapeutics at telephone 1-800-526-7736, to FDA at telephone 1-800-332-1088 or at http://www.fda.gov/medwatch , and to CDC's Emergency Operations Center at telephone 1-770-488-7100.

Dr. Udwadia of PD Hinduja Hospital, Mumbai  on  r treatment of XDR heres the link  : http://cid.oxfordjournals.org/content/early/2011/11/24/cid.cir889.extract

you should contact Dr. Homa Mansoor at the MSF Mumbai DR TB Clinic in Mumbai on this very interesting question. Her email is [email protected]

There is an interesting and applicable commentary in Lancet Infectious Disease this week.