Pradhan et al Journal of Drug Delivery & Therapeutics; 2014, 4(5), 69-73 69 © 2011-14, JDDT. All Rights Reserved ISSN: 2250-1177 CODEN (USA): JDDTAO Available online on 15.09.2014 at http://jddtonline.info Journal of Drug Delivery and Therapeutics Open access to Pharmaceutical and Medical research © 2014, publisher and licensee JDDT, This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited REVIEW ARTICLE ADVANCES IN ANTI-TUBERCULOSIS DRUGS Dr. Pradhan Sapna *, Dr.(Col) Mathur A G, Dr. Patil Amol Dept of Pharmacology, Army College of Medical Sciences, Delhi Cantt, India-110010 *Corresponding Author’s email: drsapnapradhan@gmail.com INTRODUCTION Human tuberculosis (TB) is caused by infection with members of the Mycobacterium tuberculosis complex, which includes Mycobacterium tuberculosis itself, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti, Mycobacterium pinnipedii and Mycobacterium canettii 1,2. Patients with active pulmonary TB are the main sources of infection and the majority of people infected with M. tuberculosis contain it as asymptomatic latent TB infection (LTBI). An estimated 2 billion people have LTBI and are at risk of re-activation of the disease 1,3,4 . TB continues to spread in every corner of the globe despite the introduction of the inexpensive and effective quadruple drug therapy regimen 40 years ago 5 The seventeenth World Health Organization (WHO) report on the worldwide incidence of TB 6 indicates that TB remains a global emergency. India, China, South Africa and the Russian Federation have almost 60% of the world‟s TB cases 6 ` Multidrug-resistant TB (MDR-TB) is now widespread globally with an esti- mated half a million cases reported in 2011, and extensively drug-resistant TB (XDR-TB) has been reported in 84 countries. TB treatment is challenging, requiring accurate and early diagnosis, drug-resistance screening and the administration of effective treatment regimens for at least 6 months through directly observed therapy (DOT) and follow-up support. There is an urgent need for the devel- opment and more efficient evaluation of new TB drugs and shorter treatment regimens.. Over the past 10 years, significant investment by scientists, funding bodies and high-profile advocacy by the WHO‟s STOP TB depart - ment, and other organizations, has led to a renaissance of activity in the discovery and development of new TB drugs and TB treatment regimens. These efforts have culminated in historic advances in TB therapeutics, including the recent submissions to regulatory agencies for approval of two new drugs: delamanid (previously known as OPC67683) and bedaquiline (also known as TMC207 or R207910) CURRENT TUBERCULOSIS TREATMENT REGIMENS Drug-susceptible tuberculosis. Nearly 60 years follow- ing the identification of the first antibiotic active against M. tuberculosis, the current recommended treatment of drug-susceptible TB is of at least 6 months duration and achieves cure rates of >95% when administered under DOT. Treatment requires a minimum of 6 months in two phases: 2 months of four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) in the intensive phase followed by 4 months of isoniazid plus rifampicin in the continuation stage (the so-called short-course chemo- therapy). This regimen is currently implemented for pulmonary TB and most forms of extrapulmonary TB regardless of HIV status 7,8. However, there are significant challenges associated with current therapy including the following: drug intolerance and toxicities, with the resultant need for treatment interruptions and changes to the regimen; pharmacokinetic drug–drug interactions, particularly with antiretroviral therapy (ART) drugs in patients co-infected with TB and HIV; and patient adherence given the lengthy treatment duration necessary to achieve non-relapsing cure. The absence of concerted drug development and new combinations for decades has paradoxically paved the way for introduction of fixed- dose combinations of two (isoniazid and rifampicin), three (isoniazid, rifampicin and pyrazinamide) and four (isoniazid, rifampicin, pyrazinamide and ethambutol) drugs 9 . Given that most of the world‟s TB burden is caused by drug-susceptible strains of M. tuberculosis, the ABSTRACT Despite the introduction 40 years ago of the inexpensive and effective four-drug (isoniazid, rifampicin, pyrazinamide and ethambutol) treatment regimen, tuberculosis (TB) continues to cause considerable morbidity and mortality worldwide. For the first time since the 1960s, new and novel drugs and regimens for all forms of TB are emerging. Such regimens are likely to utilize both repurposed drugs and new chemical entities, and several of these regimens are now progressing through clinical trials. This article covers current concepts and recent advances in TB drug discovery and development. Key Words: MDR-TB, XDR-TB, TDR-TB, Bedaquiline, Delamanid