Multidrug-resistant tuberculosis: a menace that threatens to destabilize tuberculosis control.

Multidrug-resistant tuberculosis (MDR-TB), caused by Mycobacterium tuberculosis that is resistant to both isoniazid and rifampicin with or without resistance to other drugs, is a phenomenon that is threatening to destabilize global tuberculosis (TB) control. MDR-TB is a worldwide problem, being present virtually in all countries that were surveyed. According to current World Health Organization and the International Union Against Tuberculosis and Lung Disease estimates, the median prevalence of MDR-TB has been 1.1% in newly diagnosed patients. The proportion, however, is considerably higher (median prevalence, 7%) in patients who have previously received anti-TB treatment. While host genetic factors may contribute to the development of MDR-TB, incomplete and inadequate treatment is the most important factor leading to its development, suggesting that it is often a man made tragedy. Efficiently run TB control programs based on a policy of directly observed treatment, short course (DOTS), are essential for preventing the emergence of MDR-TB. The management of MDR-TB is a challenge that should be undertaken by experienced clinicians at centers equipped with reliable laboratory services for mycobacterial cultures and in vitro sensitivity testing as it the requires prolonged use of costly second-line drugs with a significant potential for toxicity. The judicious use of drugs; supervised standardized treatment; focused clinical, radiologic, and bacteriologic follow-up; and surgery at the appropriate juncture are key factors in the successful management of these patients. With newer effective anti-TB drugs still a distant dream, innovative approaches such as DOTS-Plus are showing promise for the management of patients with MDR-TB under program conditions and appear to be a hope for future.

[1]  D. Maher,et al.  Guidelines for the Management of Drug-resistant Tuberculosis , 1997 .

[2]  L. Karasulu,et al.  The treatment of multidrug-resistant tuberculosis in Turkey. , 2001, The New England journal of medicine.

[3]  S. Rüsch-Gerdes,et al.  A case-control study for multidrug-resistant tuberculosis: risk factors in four European countries. , 2005, Microbial drug resistance.

[4]  S. Niemann,et al.  The Beijing genotype is a major cause of drug-resistant tuberculosis in Kazakhstan. , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[5]  F. Drobniewski,et al.  Molecular Techniques in the Diagnosis of Mycobacterium tuberculosis and the Detection of Drug Resistance , 2001, Annals of the New York Academy of Sciences.

[6]  R. O'brien,et al.  The use of restriction fragment length polymorphism (RFLP) analysis for epidemiological studies of tuberculosis in developing countries. , 1998, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[7]  H S F Fraser,et al.  Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis. , 2005, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[8]  R. Baltussen,et al.  Cost effectiveness analysis of strategies for tuberculosis control in developing countries , 2005, BMJ : British Medical Journal.

[9]  Robert C. Reynolds,et al.  Preclinical Testing of the Nitroimidazopyran PA-824 for Activity against Mycobacterium tuberculosis in a Series of In Vitro and In Vivo Models , 2005, Antimicrobial Agents and Chemotherapy.

[10]  I. Bastian,et al.  Detection of rifampicin resistance in Mycobacterium tuberculosis isolates from diverse countries by a commercial line probe assay as an initial indicator of multidrug resistance. , 2000, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[11]  L. Blumberg,et al.  Rapid indication of multidrug-resistant tuberculosis from liquid cultures using FASTPlaqueTB-RIF, a manual phage-based test. , 2002, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[12]  S. Sharma,et al.  Progress of DOTS in global tuberculosis control , 2006, The Lancet.

[13]  Naresh J. Patel,et al.  Effect of an immunomodulator containing Mycobacterium w on sputum conversion in pulmonary tuberculosis. , 2002, Journal of the Indian Medical Association.

[14]  V. Jarlier,et al.  Outcome of multi-drug-resistant tuberculosis in France: a nationwide case-control study. , 1999, American journal of respiratory and critical care medicine.

[15]  L. P. Ormerod Multidrug-resistant tuberculosis (MDR-TB): epidemiology, prevention and treatment. , 2005, British medical bulletin.

[16]  N. Ahmed,et al.  Mycobacterium tuberculosis Isolate with a Distinct Genomic Identity Overexpresses a Tap-Like Efflux Pump , 2004, Infection.

[17]  Nalin Rastogi,et al.  Predominant Tuberculosis Spoligotypes, Delhi, India , 2004, Emerging infectious diseases.

[18]  M. Putman,et al.  Molecular Properties of Bacterial Multidrug Transporters , 2000, Microbiology and Molecular Biology Reviews.

[19]  J. Musser,et al.  Analysis of the oxyR-ahpC region in isoniazid-resistant and -susceptible Mycobacterium tuberculosis complex organisms recovered from diseased humans and animals in diverse localities , 1997, Antimicrobial agents and chemotherapy.

[20]  Naresh J. Patel,et al.  Improved cure rates in pulmonary tuberculosis category II (retreatment) with mycobacterium w. , 2003, Journal of the Indian Medical Association.

[21]  P. Small,et al.  Does DOTS work in populations with drug-resistant tuberculosis? , 2005, The Lancet.

[22]  S. Niemann,et al.  The Beijing genotype and drug resistant tuberculosis in the Aral Sea region of Central Asia , 2005, Respiratory research.

[23]  T. Frieden,et al.  The DOTS strategy for controlling the global tuberculosis epidemic. , 2005, Clinics in chest medicine.

[24]  T. Tupasi,et al.  Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative. , 2004, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[25]  N. Binkin,et al.  Determinants of drug-resistant tuberculosis: analysis of 11 countries. , 2001, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[26]  R. O'brien,et al.  New drugs for tuberculosis: current status and future prospects. , 2005, Clinics in chest medicine.

[27]  N. Ahmed,et al.  Genomics of Mycobacterium tuberculosis: old threats & new trends. , 2004, The Indian journal of medical research.

[28]  J. Musser,et al.  Molecular diagnosis of mycobacteria. , 2001, Clinical chemistry.

[29]  D. Snider,et al.  Multidrug-resistant Tuberculosis , 1992, Annals of Internal Medicine.

[30]  J. Grange,et al.  Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis. , 2004, Frontiers in bioscience : a journal and virtual library.

[31]  Philip Supply,et al.  Automated High-Throughput Genotyping for Study of Global Epidemiology of Mycobacterium tuberculosis Based on Mycobacterial Interspersed Repetitive Units , 2001, Journal of Clinical Microbiology.

[32]  F. Drobniewski,et al.  A national study of clinical and laboratory factors affecting the survival of patients with multiple drug resistant tuberculosis in the UK , 2002, Thorax.

[33]  Donna Neuberg,et al.  Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. , 2003, The New England journal of medicine.

[34]  T. Holtz,et al.  Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study , 2005, The Lancet.

[35]  K. Mate,et al.  From multidrug-resistant tuberculosis to DOTS expansion and beyond: making the most of a paradigm shift. , 2003, Tuberculosis.

[36]  J. Stanford,et al.  Immunotherapy for drug-resistant tuberculosis , 1992, The Lancet.

[37]  R. Coninx,et al.  First-line tuberculosis therapy and drug-resistant Mycobacterium tuberculosis in prisons , 1999, The Lancet.

[38]  W. Rom,et al.  Outcome of MDR-TB patients, 1983-1993. Prolonged survival with appropriate therapy. , 1996, American journal of respiratory and critical care medicine.

[39]  Molecular Genotyping of a Large, Multicentric Collection of Tubercle Bacilli Indicates Geographical Partitioning of Strain Variation and Has Implications for Global Epidemiology of Mycobacterium tuberculosis , 2004, Journal of Clinical Microbiology.

[40]  J. T. Crawford,et al.  An outbreak of multidrug-resistant tuberculosis among hospitalized patients with the acquired immunodeficiency syndrome. , 1992, The New England journal of medicine.

[41]  Preeti Gupta,et al.  Ring-substituted imidazoles as a new class of anti-tuberculosis agents. , 2004, European journal of medicinal chemistry.

[42]  L. Lambert,et al.  Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. , 2005, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[43]  S. Asch,et al.  Relationship of isoniazid resistance to human immunodeficiency virus infection in patients with tuberculosis. , 1996, American journal of respiratory and critical care medicine.

[44]  A. Mohan,et al.  Scientific basis of directly observed treatment, short-course (DOTS). , 2003, Journal of the Indian Medical Association.

[45]  N. K. Jain,et al.  Clinical and genetic risk factors for the development of multi-drug resistant tuberculosis in non-HIV infected patients at a tertiary care center in India: a case-control study. , 2003, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[46]  J. T. Crawford,et al.  Transmission of multidrug-resistant Mycobacterium tuberculosis among persons with human immunodeficiency virus infection in an urban hospital: epidemiologic and restriction fragment length polymorphism analysis. , 1993, The Journal of infectious diseases.

[47]  A. Alrajhi,et al.  Risk factors for drug-resistant Mycobacterium tuberculosis in Saudi Arabia. , 2002, Saudi medical journal.

[48]  M. Espinal,et al.  Increasing transparency in partnerships for health – introducing the Green Light Committee , 2002, Tropical medicine & international health : TM & IH.

[49]  G. Peersman,et al.  A survey of drug-resistant Mycobacterium tuberculosis and its relationship to HIV infection. , 1998 .

[50]  F. Drobniewski,et al.  The use of macroarrays for the identification of MDR Mycobacterium tuberculosis. , 2006, Journal of microbiological methods.

[51]  Charles L Daley,et al.  American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. , 2003, American journal of respiratory and critical care medicine.

[52]  A. Mirzabekov,et al.  Evaluation of hybridisation on oligonucleotide microarrays for analysis of drug-resistant Mycobacterium tuberculosis. , 2005, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[53]  A. Fraser,et al.  Treatment of latent tuberculosis in persons at risk for multidrug-resistant tuberculosis: systematic review. , 2006, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[54]  A. Khomenko,et al.  Standard short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6 countries. , 2000, JAMA.

[55]  R. Urbanczik,et al.  Laboratory diagnostic aspects of drug resistant tuberculosis. , 2004, Frontiers in bioscience : a journal and virtual library.

[56]  S. Han,et al.  Association of HLA-DR and HLA-DQ genes with susceptibility to pulmonary tuberculosis in Koreans: preliminary evidence of associations with drug resistance, disease severity, and disease recurrence. , 2005, Human immunology.

[57]  Hinrich W. H. Göhlmann,et al.  A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis , 2005, Science.

[58]  Clifton E. Barry,et al.  A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis , 2000, Nature.

[59]  J. Musser,et al.  Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. , 1998, Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.