Journal of Biosciences

, 33:605 | Cite as

Multidrug resistant to extensively drug resistant tuberculosis: What is next?

  • Amita Jain
  • Pratima Dixit


Drug resistant tuberculosis is a man made problem. While tuberculosis is hundred percent curable, multidrug resistant tuberculosis (MDR-TB) is difficult to treat. Inadequate and incomplete treatment and poor treatment adherence has led to a newer form of drug resistance known as extensively drug resistant tuberculosis (XDR-TB). XDR-TB is defined as tuberculosis caused by Mycobacterium tuberculosis strain, which is resistant to at least rifampicin and isoniazid among the first line anti tubercular drugs (MDR-TB) in addition to resistance to any fluroquinolones and at least one of three injectable second line anti tubercular drugs i.e. amikacin, kanamycin and/or capreomycin. Mismanagement of tuberculosis paves the way to drug resistant tuberculosis. Emergence of XDR-TB is reported world wide. Reported prevalence rates of XDR-TB of total MDR cases are; 6.6% overall worldwide, 6.5% in industrialized countries, 13.6% in Russia and Eastern Europe, 1.5% in Asia, 0.6% in Africa and Middle East and 15.4% in Republic of Korea. Better management and control of tuberculosis specially drug resistant TB by experienced and qualified doctors, access to standard microbiology laboratory, co-morbitidy of HIV and tuberculosis, new anti-TB drug regimens, better diagnostic tests, international standards for second line drugs (SLD)-susceptibility testing, invention of newer antitubercular molecules and vaccines and knowing the real magnitude of XDR-TB are some of the important issues to be addressed for effective prevention and management of XDR-TB.


Drug resistant tuberculosis extensively drug resistant tuberculosis (XDR-TB) multidrug resistant tuberculosis (MDR-TB) 

Abbreviations used


direct observation therapy strategy


isonicotinic acid hydrazide


multi drug resistant tuberculosis


second line anti tubercular drug


supranational reference laboratories


extremely drug resistant tuberculosis


  1. Baltussen R, Floyd K and Dye C 2005 Cost effectiveness analysis of strategies for tuberculosis control in developing countries; Br. Med. J. 331 1364CrossRefGoogle Scholar
  2. Blumberg H M, Burman W J, Chaisson R E, Daley C L, Etkind S C, Friedman L N, Fujiwara P, Grzemska M, et al 2003 American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis; Am. J. Respir. Crit. Care Med. 167 603–662PubMedCrossRefGoogle Scholar
  3. Bouvet E 2007 Multidrug resistant tuberculosis: What is the risk in France?; Rev. Prat. 15 1405–1408Google Scholar
  4. Carpenter J L, Obnibene A J, Gorby E W, Neimes R E, Koch J and Perkins W L 1983 Antituberculosis drug resistance in south Texas; Am. Rev. Respir. Dis. 128 1055–1058PubMedGoogle Scholar
  5. Centers for Disease Control and Prevention 2006 Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs-worldwide; MMWR 55 301–305Google Scholar
  6. Chan E D and Iseman M D 2002 Current medical treatment for tuberculosis; Br. Med. J. 325 1282–1286CrossRefGoogle Scholar
  7. Datta M, Radhamani M P, Selvaraj R, Paramasivan C N, Gopalan B N, Sudeendra C R and prabhakar R, et al 1993 Critical assessment of smear-positive pulmonary tuberculosis patients after chemotherapy under the district tuberculosis programme; Tuber. Lung Dis. 74 180–186PubMedCrossRefGoogle Scholar
  8. DeRiemer K, Garcia-Garcia L and Bobadilla-del-Valle M 2005 Does DOTS work in populations with drug-resistant tuberculosis?; Lancet 365 1239–1245PubMedCrossRefGoogle Scholar
  9. Drobniewski F A and Balabanova Y M 2002 The diagnosis and management of multiple-drug-resistant tuberculosis at the beginning of the new millennium; Int. J. Infect. Dis. 6 S21–S31PubMedCrossRefGoogle Scholar
  10. Drobniewski F, Eltringham I, Graham C, Magee J G, Smith E G and Watt B 2002 A national study of clinical and laboratory factors affecting the survival of patients with multiple drug resistant tuberculosis in the UK; Thorax 5723 810–816PubMedCrossRefGoogle Scholar
  11. Editorial 2007 Stopping tuberculosis proves hard to do; Lancet 369 965CrossRefGoogle Scholar
  12. Espinal M A and Dye C 2005 Can DOTS control multidrug-resistant tuberculosis?; Lancet 365 1206–1209PubMedCrossRefGoogle Scholar
  13. Espinal M A, Dye C, Raviglione M, et al 1999 Rational ‘DOT plus’ for the control of MDR-TB; Int. Tuberc. Lung Dis. 3 561–563Google Scholar
  14. Espinal M A, Kim S J, Suarez P G, et al 2000 Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries. JAMA 283 2537–2545PubMedCrossRefGoogle Scholar
  15. Farmer P and Kim J Y 1998 Community based approaches to the control of multidrug resistant tuberculosis: introducing “DOTS-plus”; Br. Med. J. 317 671–674Google Scholar
  16. Flament-Saillour M, Robert J, Jarlier V, et al 1999 Outcome of multi-drug-resistant tuberculosis in France: a nationwide case-control study; Am. J. Respir. Crit. Care Med. 160 587–593PubMedGoogle Scholar
  17. Floyd K, Hutubessy R, Samyshkin E, et al 2006 Health-systems efficiency in the Russian Federation: tuberculosis control. Bull.WHO 84 43–51PubMedGoogle Scholar
  18. Gandhi N R, Moll A and Sturm A W 2006 Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa; Lancet 368 1575–1580PubMedCrossRefGoogle Scholar
  19. Giovanni Di Perri and Stefano Bonora 2004 Which agents should we use for the treatment of multidrug- resistant Mycobacterium tuberculosis?; J. Antimicrob. Chemother. 54 593–602CrossRefGoogle Scholar
  20. Goble M, Iseman M D, Madsen L A, et al 1993 Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampicin; N. Engl. J. Med. 328 527–532PubMedCrossRefGoogle Scholar
  21. Gupta R, Cegielski J P, Espinal M A, et al 2002 Increasing transparency for health: introducing the Green Light Committee; Trop. Med. Int. Health 7 970–976PubMedCrossRefGoogle Scholar
  22. Gupta R and Espinal M and Stop TB Working Group on DOTS-Plus for MDR-TB 2003 A prioritised research agenda for DOTS-Plus for multidrug-resistant tuberculosis (MDR-TB); Int. J. Tuberc. Lung Dis. 7 410–414PubMedGoogle Scholar
  23. Gupta R, Raviglione and Espinal M A 2001 Should tuberculosis programmes invest in second line treatments for multidrug-resistant tuberculosis (MDR-TB)?; Int. J. Tuberc. Lung Dis. 5 1078–1079PubMedGoogle Scholar
  24. Heifets L B and Cangelosi G A 1999 Drug susceptibility testing of Mycobacterium tuberculosis: a neglected problem at the turn of the century; Int. J. Tuberc. Lung Dis. 3 564–581PubMedGoogle Scholar
  25. Holtz T H, Riekstina V, Zarovska E, et al 2005 XDR-TB: extreme drug-resistance and treatment outcome under DOTS-Plus, Latvia, 2000–2002; Int. J. Tuberc. Lung Dis. (Suppl. 1) 9 S258Google Scholar
  26. Hopewell P C, Pai M, Maher D, et al 2006 International standards for Tuberculosis care; Lancet Infect. Dis. 6 710–725PubMedCrossRefGoogle Scholar
  27. Huong N T, Lan N T, Cobelens F G, et al 2006 Antituberculosis drug resistance in the south of Vietnam: prevalence and trends; J. Infect. Dis. 194 1226–1232PubMedCrossRefGoogle Scholar
  28. Iseman M D 1993 Treatment of multidrug-resistant tuberculosis. N. Engl. J. Med. 329 784–791PubMedCrossRefGoogle Scholar
  29. Jacqui W 2006 Southern Africa is moving swiftly to combat the threat of XDR-TB; Bull. WHO 84 924–925Google Scholar
  30. Jacaban R F 1994 Multiple drug Resstant Tuberculosis; Clin. Infect. Dis. 19 1–10Google Scholar
  31. Jeon C Y, Hwang S H, Min J H, et al 2008 Extensively drug-resistant tuberculosis in South Korea: risk factors and treatment outcomes among patients at a tertiary referral hospital; Clin. Infect. Dis. 46 42–49PubMedCrossRefGoogle Scholar
  32. Johnson J, Kagal A and Bharadwaj R 2003 Factors associated with drug resistance in pulmonary tuberculosis; Indian J. Chest Dis. Allied Sci. 45 105–109PubMedGoogle Scholar
  33. Kam K M and Yip C W 2004 Surveillance of Mycobacterium tuberculosis susceptibility to second-line drugs in Hong Kong, 1995–2002, after the implementation of DOTS-plus; Int. J. Tuberc. Lung Dis. 8 760–766PubMedGoogle Scholar
  34. Kato-Maeda M, Bifani P J, Krieswirth B N, et al 2001 The nature and consequence of genetic variability in Mycobacterium tuberculosis; J. Clin. Invest. 107 533–537PubMedCrossRefGoogle Scholar
  35. Kato-Maeda, M, Rhee J T, Gingeras T R, et al 2001 Comparing genomes within the species Mycobacterium tuberculosis; Genome Res. 11 547–555PubMedCrossRefGoogle Scholar
  36. Kim H R, Hwang S S, Kim H J, et al 2007 Impact of extensive drug resistance on treatment outcomes in non-HIV-infected patients with multidrug-resistant tuberculosis; Clin. Infect. Dis. 45 1290–1295PubMedCrossRefGoogle Scholar
  37. Leimane V, Rickstina V, Holtz T H, et al 2005 Clinical outcome of individualized treatment of multidrug resistant tuberculosis in Latvia: A retrospective cohort study; Lancet 365 318–326PubMedGoogle Scholar
  38. Masjedi M R, Farnia P, Sorooch S, et al 2006 Extensively drug-resistant tuberculosis: 2 years of surveillance in Iran; Clin. Infect. Dis. 43 841–847PubMedCrossRefGoogle Scholar
  39. Matteelli A, Migliori G B, Cirillo D, et al 2007 Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis: epidemiology and control; Exp. Rev. Anti Infect. Ther. 5 857–871CrossRefGoogle Scholar
  40. Migliori G B, Loddenkemper R, Blasi F, et al 2007a 125 years after Robert Koch’s discovery of the tubercle bacillus: the new XDR-TB threat. Is “science” enough to tackle the epidemic?; Eur. Respir. J. 29 423–427PubMedCrossRefGoogle Scholar
  41. Migliori G, Ortman J, Giardi E, et al 2007b Extensively drug-resistant tuberculosis, Italy and Germany; Emerg. Infect. Dis. 13 1–4Google Scholar
  42. Mitnick C, Bayona J, Palacios E, et al 2003 Community-based therapy for multidrug- resistant tuberculosis in Lima, Peru; N. Engl. J. Med. 348 119–128PubMedCrossRefGoogle Scholar
  43. Mlambo C K, Warren R M, Poswa X, et al 2008 Genotypic diversity of extensively drug-resistant tuberculosis (XDR-TB) in South Africa; Int. J. Tuberc. Lung Dis. 12 99–104PubMedGoogle Scholar
  44. Mondal R and Jain A 2007 Extensively Drug-Resistant Mycobacterium tuberculosis, India; Emerg. Infect. Dis. 13 1429–1431PubMedGoogle Scholar
  45. Mukherjee J S, Rich M L, Socci AR, et al 2004 Programmes and principles in treatment of multidrug- resistant tuberculosis; Lancet 363 474–481PubMedCrossRefGoogle Scholar
  46. Mwinga A 2001 Drug resistant tuberculosis in Africa; Ann. N. Y. Acad. Sci. 953 106–112PubMedCrossRefGoogle Scholar
  47. Narain J P and Lo Y R 2004 Epidemiology of HIV-TB in Asia; Indian J. Med. Res. 120 277–289PubMedGoogle Scholar
  48. Nathanson E, Lambregts-van Wezenbeek C, Rich M L, et al 2006 Multidrug-resistant tuberculosis management in resource-limited settings; Emerg. Infect. Dis. 12 1389–1397PubMedGoogle Scholar
  49. Ormerod L P 2005 Multidrug-resistant tuberculosis (MDR-TB): epidemiology, prevention and treatment; Br. Med. Bull. 73–74 17–24PubMedCrossRefGoogle Scholar
  50. Park M H, Song E Y, Park H J, et al 2002 HLA-DRB1 and DQB1 gene polymorphism is associated with multidrug-resistant tuberculosis in Korean patients; Hum. Immunol. 63 S33CrossRefGoogle Scholar
  51. Park M M, Davis A L, Schluger N W, et al 1996 Outcome of MDRTB patients, 1983–1993. Prolonged survival with appropriate therapy; Am. J. Respir. Crit. Care Med. 153 317–324PubMedGoogle Scholar
  52. Pillay M and Sturm A W 2007 Evolution of the extensively drug-resistant F15/LAM4/KZN strain of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa; Clin. Infect. Dis. 45 1409–1414PubMedCrossRefGoogle Scholar
  53. Prasad R 2005 MDR TB: Current Status; Indian J. Tuberc. 52 121–131Google Scholar
  54. Prasad R and Garg R 2007 XDR-TB: An emerging threat; Chest India 8 3–4Google Scholar
  55. Prasad R, Nautiyal R G, Mukherji P K, et al 2002 Treatment of new pulmonary tuberculosis patients: what do allopathic doctors do in India?; Int. J. Tuberc. Lung Dis. 6 895–902PubMedGoogle Scholar
  56. Rajbhandary S S, Marks S M and Bock N N 2004 Cost of patients hospitalized for multidrug resistant tuberculosis; Int. J. Tuberc. Lung Dis. 8 1012–1016PubMedGoogle Scholar
  57. Rai S P and Panda B N 2004 Outcome in Multidrug Resistant Tuberculosis patients with ambulatory treatment; Indian J. Tuberc. 51 33–36Google Scholar
  58. Ramaswamy S and Musser J M 1998 Molecular genetic basis of anti-microbial agent resistance in Mycobacterium tuberculosis: 1998 update; Tuber. Lung Dis. 79 3–29PubMedCrossRefGoogle Scholar
  59. Shah S N, Wright A and Drobniewski F 2005 Extreme drug resistance in tuberculosis (“XDR-TB”): global survey of supranational reference laboratories for Mycobacterium tuberculosis with resistance to second-line drugs; Int. J. Tuberc. Lung Dis. (Suppl 1) 9 S77Google Scholar
  60. Shah S N, Wright, A, Bai H G, et al 2007 Worldwide emergence of extensively drug-resistant tuberculosis; Emer. Infect. Dis. 13 380–387CrossRefGoogle Scholar
  61. Sharma S K and Mohan A 2006 Multidrug-resistant tuberculosis: a menace that threatens to destabilize tuberculosis control; Chest 130 261–272PubMedCrossRefGoogle Scholar
  62. Sharma S K and Mohan A 2004 Multidrug-resistant tuberculosis; Indian J. Med. Res. 120 354–376PubMedGoogle Scholar
  63. Sharma S K and Mohan A 2003 Scientific basis of directly observed treatment, short course (DOTS); J. Indian Med. Assoc. 101 157–158,166PubMedGoogle Scholar
  64. Sharma S K, Turaga K K, Balamurugan A, et al 2003 Clinical and genetic risk factors for the development of multidrug-resistant tuberculosis in non-HIV infected patients at a tertiary care center in India: a case-control study; Infect. Genet. Evol. 3 183–188PubMedCrossRefGoogle Scholar
  65. Singh S, Sankar M M and Gopinath K 2008 High rate of extensively drug-resistant tuberculosis in Indian AIDS patients; AIDS 21 2345–2347Google Scholar
  66. Stop T B Partnership 2006 The STOP TB strategy: building on and enhancing DOTS to meet the TB-related millennium development goals (Geneva: World Health Organization)Google Scholar
  67. Tahaoglu K, Torun T, Sevim T, et al 2001 The treatment of multidrug-resistant tuberculosis in Turkey; N. Engl. J. Med. 345 170–174PubMedCrossRefGoogle Scholar
  68. Thomas A, Ramachandran R, Rehaman F, et al 2007 Management of multidrug resistance tuberculosis in the field: Tuberculosis Research Centre experience; Indian J. Tuberc. 54 117–124PubMedGoogle Scholar
  69. Tomioka H 2002 Prospects for development of new antituberculous drug; Kekkaku 77 573–584PubMedGoogle Scholar
  70. Tomioka H and Namba K 2006 Development of antituberculous drugs: current status and future prospects; Kekkaku 81 753–774PubMedGoogle Scholar
  71. Uplekar M 2003 Involving private health care providers in delivery of TB care: Global Strategy; Tuberculosis 83 156–164PubMedCrossRefGoogle Scholar
  72. Uplekar M W and Shepard D S 1991 Treatment of tuberculosis by private general practiceners in India; Tubercle 72 284–290PubMedCrossRefGoogle Scholar
  73. Van Deum A, Salim M A, Das A P, Bastian I and Potales F 2004 Results of a standardized regimen for multidrug resistant tuberculosis in Bangladesh; Int. J. Tuberc. Lung Dis. 8 560–567Google Scholar
  74. Weyer K and Kleeberg H H 1992 Primary and acquired drug resistance in adult black patients with tuberculosis in South Africa: results of a continuous national drug resistance surveillance programme involvement; Tuber. Lung Dis. 73 106–112PubMedCrossRefGoogle Scholar
  75. World Health Organization Report 2008 Global Tuberculosis Control pp 109–112Google Scholar
  76. World Health Organization 2006 Extensively drug-resistant tuberculosis (XDR.TB): recommendations for prevention and control; Weekly Epidemiol. Rec. 81 430–432Google Scholar

Copyright information

© Indian Academy of Sciences 2008

Authors and Affiliations

  1. 1.Post Graduate Department of MicrobiologyCSM Medical UniversityLucknowIndia

Personalised recommendations