Respiratory Medicine
Volume 103, Issue 12 , Pages 1777-1790 , December 2009

Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis

  • Suhail Ahmad

      Affiliations

    • Corresponding Author InformationCorrespondence to: Suhail Ahmad, Department of Microbiology, Faculty of Medicine, AMAR Health Sciences Center, Kuwait University, P. O. Box 24923, Safat 13110, Kuwait. Tel.: +965 2498 6503; fax: +965 2531 8454.
  • ,
  • Eiman Mokaddas

Received 30 March 2009 ,Accepted 19 July 2009.

References 

  1. World Health Organization . Global tuberculosis control: surveillance, planning and financing. WHO report 2008. WHO/HTM/TB/2008.393 Geneva, Switzerland: WHO; 2008;
  2. Frieden TR, Sterling TR, Munsiff SS, Watt CJ, Dye C. Tuberculosis. Lancet. 2003;362:887–899
  3. Wells CD, Cegielski JP, Nelson LJ, et al. HIV infection and multidrug-resistant tuberculosis-the perfect storm. J Infect Dis. 2007;196(Suppl. 1):S86–107
  4. Medical Research Council . Streptomycin treatment of pulmonary tuberculosis: a Medical Research Council Investigation. Br Med J. 1948;4582:769–782
  5. Mitchison DA. The action of antituberculosis drugs in short-course chemotherapy. Tubercle. 1985;66:219–225
  6. Mitchison DA. The diagnosis and therapy of tuberculosis during the past 100 years. Am J Respir Crit Care Med. 2005;171:699–706
  7. American Thoracic SocietyCDCInfectious Disease Society of America. Treatment of tuberculosis. MMWR Morb Mortal Wkly Rep. 2003;52:1–77
  8. Palaci M, Dietze R, Hadad DJ, et al. Cavitary disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J Clin Microbiol. 2007;45:4064–4066
  9. World Health Organization . Anti-tuberculosis drug resistance in the world: fourth Global report. WHO/HTM/TB/2008.394 Geneva, Switzerland: WHO; 2008;
  10. Drobniewski F, Balabanova Y, Ruddy M. Rifampin- and multidrug-resistant tuberculosis in Russian civilians and prison inmates: dominance of the Beijing strain family. Emerg Infect Dis. 2002;8:1320–1326
  11. Kimerling ME, Phillips P, Patterson P, Hall M, Robinson CA, Dunlap NE. Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients. Chest. 1998;113:1178–1183
  12. Mokaddas E, Ahmad S, Abal AT, Al-Shami AS. Molecular fingerprinting reveals familial transmission of rifampin-resistant tuberculosis in Kuwait. Ann Saudi Med. 2005;25:150–153
  13. Aziz MA, Wright A, Laszlo A, et al. for the WHO/International Union Against Tuberculosis and Lung Disease global project on anti-tuberculosis drug resistance surveillance. Epidemiology of antituberculosis drug resistance (the Global Project on Anti-tuberculosis Drug Resistance Surveillance): an updated analysis. Lancet. 2006;368:2142–2154
  14. Zignol M, Hosseini MS, Wright A, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis. 2006;194:479–485
  15. Mitnick CD, Castro KG, Harrington M, Sacks LV, Burman W. Randomized trials to optimize treatment of multidrug-resistant tuberculosis. PLoS Med. 2007;4:e292
  16. Centers for Disease Control and Prevention (CDC) . Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs-worldwide, 2000–2004. MMWR Morb Mortal Wkly Rep. 2006;55:301–305
  17. Dye C. Doomsday postponed? Preventing and reversing epidemics of drug-resistant tuberculosis. Nat Rev Microbiol. 2009;7:81–87
  18. Gandhi NR, Moll A, Sturn AW, et al. 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. 2006;368:1554–1556
  19. Zhang Y, Heym B, Allen B, Young D, Cole ST. The catalase–peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature. 1992;358:591–593
  20. Telenti A, Imboden P, Marchesi F, et al. Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet. 1993;341:647–650
  21. Vilcheze C, Wang F, Arai M, et al. Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid. Nat Med. 2006;12:1027–1029
  22. Ramaswamy S, Musser JM. Molecular genetics basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber Lung Dis. 1998;79:3–29
  23. Johnson R, Streicher E, Louw G, Warren RM, van Helden PD, Victor TC. Drug resistance in Mycobacterium tuberculosis. Curr Issues Mol Biol. 2006;8:97–111
  24. Ramaswamy S, Reich R, Dou S, et al. Single nucleotide polymorphisms in genes associated with isoniazid resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2003;47:1241–1250
  25. Abal AT, Ahmad S, Mokaddas E. Variations in the occurrence of the S315T mutation within the katG gene in isoniazid-resistant clinical Mycobacterium tuberculosis isolates from Kuwait. Microb Drug Resist. 2002;8:99–105
  26. Mokrousov I, Narvskaya O, Otten T, Limeschencko E, Steklova L, Vyshnevskiy B. High prevalence of Ser315Thr substitution among isoniazid-resistant Mycobacterium tuberculosis clinical isolates of from Northwestern Russia, 1996–2001. Antimicrob Agents Chemother. 2002;46:1417–1424
  27. Silva MSN, Senna SG, Ribeiro MO, et al. Mutations in katG, inhA, and ahpC genes of Brazilian isoniazid-resistant isolates of Mycobacterium tuberculosis. J Clin Microbiol. 2003;41:4471–4474
  28. Hazbon MH, Brimacombe M, del Valle MB, et al. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2006;50:2640–2649
  29. Mokaddas E, Ahmad S, Samir I. Secular trends in susceptibility patterns of Mycobacterium tuberculosis isolates in Kuwait, 1996–2005. Int J Tuberc Lung Dis. 2008;12:319–325
  30. Van Rie A, Warren R, Mshanga I, et al. Analysis for a limited number of gene codons can predict drug resistance of Mycobacterium tuberculosis in a high-incidence community. J Clin Microbiol. 2001;39:636–641
  31. Siddiqi N, Shamim M, Hussain S, et al. Molecular characterization of multidrug-resistant isolates of Mycobacterium tuberculosis from patients in North India. Antimicrob Agents Chemother. 2002;46:443–450
  32. Afanas'ev MV, Ikryannikova LN, Il'ina EN, et al. Molecular characteristics of rifampicin- and isoniazid resistant Mycobacterium tuberculosis isolates from Russian Federation. J Antimicrob Chemother. 2007;59:1057–1064
  33. Ahmad S, Mokaddas E, Fares E. Characterization of rpoB mutations in rifampin-resistant clinical Mycobacterium tuberculosis isolates from Kuwait and Dubai. Diagn Microbiol Infect Dis. 2002;44:245–252
  34. Sheng J, Li J, Sheng G, et al. Characterization of rpoB mutations associated with rifampin resistance in Mycobacterium tuberculosis from eastern China. J Appl Microbiol. 2008;105:904–911
  35. Heep M, Brandstatter B, Rieger U, et al. Frequency of rpoB mutations inside and outside the cluster I region in rifampin-resistant clinical Mycobacterium tuberculosis isolates. J Clin Microbiol. 2001;39:107–110
  36. Ahmad S, Mokaddas E. The occurrence of rare rpoB mutations in rifampicin-resistant Mycobacterium tuberculosis isolates from Kuwait. Int J Antimicrob Agents. 2005;26:205–212
  37. Yang B, Koga H, Ohno H, et al. Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis. J Antimicrob Chemother. 1998;42:621–628
  38. Cavusoglu C, Karaca-Derici Y, Bilgic A. In-vitro activity of rifabutin against rifampicin-esistant Mycobacterium tuberculosis isolates with known rpoB mutations. Clin Microbiol Infect. 2004;10:662–665
  39. Scorpio A, Zhang Y. Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat Med. 1996;2:662–667
  40. Sekiguchi JI, Nakamura T, Miyoshi-Akiyama T, et al. Development and evaluation of a line probe assay for rapid identification of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis strains. J Clin Microbiol. 2007;45:2802–2807
  41. Ramaswamy S, Amin AG, Koksel S, et al. Molecular genetic analysis of nucleotide polymorphisms associated with ethambutol resistance in human isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2000;44:326–336
  42. Telenti A, Phillipp W, Sreevatsan S, et al. The emb operon, a unique gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med. 1997;3:567–570
  43. Safi H, Sayers B, Hazbon MH, Alland D. Transfer of embB codon 306 mutations into clinical Mycobacterium tuberculosis strains alters susceptibility to ethambutol, isoniazid and rifampin. Antimicrob Agents Chemother. 2008;52:2027–2034
  44. Starks AM, Gumusboga A, Plikaytis BB, Shinnick TM, Posey JE. Mutations at embB codon 306 are an important molecular indicator of ethambutol resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2009;53:1061–1066
  45. Ahmad S, Jaber AA, Mokaddas E. Frequency of embB codon 306 mutations in ethambutol-susceptible and -resistant clinical Mycobacterium tuberculosis isolates in Kuwait. Tuberculosis. 2007;87:123–129
  46. Sreevatsan S, Pan X, Stockbauer KE, Williams DL, Kreisworth BN, Musser JM. Characterization of rpsL and rrs mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from diverse geographic locations. Antimicrob Agents Chemother. 1996;40:1024–1026
  47. Cooksey RC, Morlock GP, McQueen A, Glickman SE, Crawford JT. Characterization of streptomycin resistance mechanisms among Mycobacterium tuberculosis isolates from patients in New York City. Antimicrob Agents Chemother. 1996;40:1186–1188
  48. Maus CE, Pilkaytis BB, Shinnick TM. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2005;49:3192–3197
  49. Maus CE, Pilkaytis BB, Shinnick TM. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2005;49:571–577
  50. Rustomjee R, Lienhardt C, Kanyok T, et al. A phase II study of the sterilizing activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2008;12:128–138
  51. Ginsburg AS, Grosset JH, Bishai WR. Fluoroquinolones, tuberculosis, and resistance. Lancet Infect Dis. 2003;3:432–442
  52. Pitaksajjakul P, Wongwit W, Punprasit W, Eampokalap B, Peacock S, Ramasoota P. Mutations in the gyrA and gyrB genes of fluoroquinolone-resistant Mycobacterium tuberculosis from TB patients in Thailand. Southeast Asian J Trop Med Public Health. 2005;36:228–237
  53. Wang JY, Lee LN, Lai HC, et al. Fluoroquinolones resistance in Mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposure. J Antimicrob Chemother. 2007;59:860–865
  54. Morlock GP, Metchock B, Sikes D, Crawford JT, Cooksey RC. ethA, inhA, and katG loci of ethionamide-resistant clinical Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother. 2003;47:3799–3805
  55. Brodie D, Schluger NW. The diagnosis of tuberculosis. Clin Chest Med. 2005;26:247–271
  56. Palomino JC. Nonconventional and new methods in the diagnosis of tuberculosis: feasibility and applicability in the field. Eur Respir J. 2005;26:339–350
  57. Cheng VCC, Yew WW, Yuen KY. Molecular diagnostics in tuberculosis. Eur J Clin Microbiol Infect Dis. 2005;24:711–720
  58. Mokaddas E, Ahmad S. Development and evaluation of a multiplex PCR for rapid detection and differentiation of Mycobacterium tuberculosis complex members from non-tuberculous mycobacteria. Jap J Infect Dis. 2007;60:140–144
  59. Tortoli E, Mariottini A, Mazarelli G. Evaluation of INNO-LiPA MYCOBACTERIA v2: improved reverse hybridization multiple DNA probe assay for mycobacterial identification. J Clin Microbiol. 2003;41:4418–4420
  60. Russo C, Tortoli E, Manichella D. Evaluation of the new Genotype Mycobacterium assay for identification of mycobacterial species. J Clin Microbiol. 2006;44:334–339
  61. Mokaddas E, Ahmad S. Species spectrum of nontuberculous mycobacteria causing infections in Kuwait. Curr Microbiol. 2008;56:413–417
  62. Tortoli E, Benedetti M, Fontanelli A, Simonetti T. Evaluation of automated BACTEC MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to four major antituberculous drugs: comparison with the radiometric BACTEC 460TB method and the agar plate method of proportion. J Clin Microbiol. 2002;40:607–610
  63. Scarparo C, Ricordi P, Ruggiaro G, Piccoli P. Evaluation of the fully automated BACTEC MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to pyrazinamide, streptomycin, isoniazid, rifampin, and ethambutol and comparison with the radiometric BACTEC 460TB method. J Clin Microbiol. 2004;42:1109–1114
  64. Piersimoni C, Olivieri A, Benacchio L, Scarparo C. Current perspective on drug susceptibility testing of Mycobacterium tuberculosis complex: the automated nonradiometric systems. J Clin Microbiol. 2006;44:20–28
  65. Rusch-Gerdes S, Pfyffer GE, Casal M, Chadwick M, Siddiqi S. Multicenter laboratory validation of the BACTEC MGIT 960 technique for testing susceptibilities of Mycobacterium tuberculosis to classical second-line and newer antimicrobials. J Clin Microbiol. 2006;44:688–692
  66. Moore DAJ, Evans CAW, Gilman RH, et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med. 2006;355:1539–1550
  67. Shiferaw G, Woldeamanuel Y, Gebeyehu M, Girmachew F, Demessie D, Lemma E. Evaluation of microscopic observation drug susceptibility assay for the detection of multidrug-resistant Mycobacterium tuberculosis. J Clin Microbiol. 2007;45:1093–1097
  68. Ejigu GS, Woldeamanuel Y, Shah NS, Gebeyehu M, Silassie A, Lemma E. Microscopic-observation drug susceptibility assay provides rapid and reliable identification of MDR-TB. Int J Tuberc Lung Dis. 2008;12:332–337
  69. Palomino JC, Martin A, Portaels F. Rapid drug resistance detection in Mycobacterium tuberculosis. a review of colourimetric methods. Clin Microbiol Infect. 2007;13:754–762
  70. Abate G, Aseffa A, Selassie A, et al. Direct colorimetric assay for rapid detection of rifampin-resistant Mycobacterium tuberculosis. J Clin Microbiol. 2004;42:871–873
  71. Martin A, Portaels F, Palomino JC. Colorimetric redox-indicator methods for the rapid detection of multidrug resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis. J Antimicrob Chemother. 2007;59:175–183
  72. Affolabi D, Odoun M, Martin A, Palomino JC, Anagonou S, Portaels F. Evaluation of direct detection of Mycobacterium tuberculosis rifampin resistance by a nitrate reductase assay applied to sputum samples in Cotonou, Benin. J Clin Microbiol. 2007;45:2123–2125
  73. Hazbon MH, Guarin N, Ferro BE, et al. Photographic and luminometric detection of luciferase reporter phages for susceptibility testing of Mycobacterium tuberculosis isolates. J Clin Microbiol. 2003;41:4865–4869
  74. Banaiee N, January V, Barthus C, et al. Evaluation of semiautomated reporter phage assay for susceptibility testing of Mycobacterium tuberculosis isolates in South Africa. Tuberculosis. 2008;88:64–68
  75. Traore H, van Deun A, Shamputa IC, Rigouts L, Portaels F. Direct detection of Mycobacterium tuberculosis complex DNA and rifampin resistance in clinical specimens from tuberculosis patients by line probe assay. J Clin Microbiol. 2006;44:4384–4388
  76. Hillemann D, Gerdes RS, Richter E. Evaluation of Genotype MTBDR plus assay for rifampin and isoniazid susceptibility testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol. 2007;45:2635–2640
  77. Feasibility of the GenoType MTBDR sl assay for fluoroquinolone, amikacin-capreomycin and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol. 2009;47:1767–1772
  78. Mokrousov I, Bhanu NV, Suffys PN, Kadival GV, Yap SF, Cho SN, et al. Multicenter evaluation of reverse line blot assay for detection of drug resistance in Mycobacterium tuberculosis clinical isolates. J Microbiol Methods. 2004;57:323–335
  79. Sougakoff W, Rodrigues M, Truffot-Pernot C, et al. Use of a high-density DNA probe array for detecting mutations involved in rifampicin resistance in Mycobacterium tuberculosis. Clin Microbiol Infect. 2004;10:289–294
  80. Bergval IL, Vijzelaar RNCP, Dalla Costa ER, et al. Development of multiplex assay for rapid characterization of Mycobacterium tuberculosis. J Clin Microbiol. 2008;46:689–699
  81. Cockerill FR, Uhl JR, Temesgen Z, et al. Rapid identification of a point mutation of the Mycobacterium tuberculosis catalase–peroxidase (katG) gene associated with isoniazid resistance. J Infect Dis. 1995;171:240–245
  82. Ahmad S, Mokaddas E, Jaber AA. Rapid detection of ethambutol-resistant Mycobacterium tuberculosis strains by PCR-RFLP targeting embB codons 306 and 497 and iniA codon 501 mutations. Mol Cell Probes. 2004;18:299–306
  83. Ahmad S, Mokaddas E. Contribution of AGC to ACC and other mutations at codon 315 of the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolates from the Middle East. Int J Antimicrob Agents. 2004;23:473–479
  84. Marttila HJ, Makinen J, Marjamaki M, Soini H. Prospective evaluation of pyrosequencing for the rapid detection of isoniazid and rifampin resistance in clinical Mycobacterium tuberculosis isolates. Eur J Clin Microbiol Infect Dis. 2009;28:33–38
  85. Ruiz M Torres MJ, Llanos AC, Arroyo A, Palomares JC, Aznar J. Direct detection of rifampin- and isoniazid-resistant Mycobacterium tuberculosis in auramine-rhodamine-positive sputum specimens by real-time PCR. J Clin Microbiol. 2004;42:1585–1589
  86. Espasa M, Gonzales-Martin J, Alcaide F, et al. Direct detection in clinical samples of multiple gene mutations causing resistance of Mycobacterium tuberculosis to isoniazid and rifampicin using fluorogenic probes. J Antimicrob Chemother. 2005;55:860–865
  87. Viveiros M, Leandro C, Rodrigues L, et al. Direct application of the INNO-LiPA Rif. TB line-probe assay for rapid identification of Mycobacterium tuberculosis complex strains and detection of resistance in 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis. J Clin Microbiol. 2005;43:4880–4884
  88. Vijdea R, Stegger M, Sosnovskaja A, Andersen AB, Thomsen VO, Bang D. Multidrug-resistant tuberculosis: rapid detection of resistance to rifampin and high or low levels of isoniazid in clinical specimens and isolates. Eur J Clin Microbiol Infect Dis. 2008;27:1079–1086
  89. Evans J, Stead MC, Nicol MP, Segal H. Rapid genotypic assays to identify drug-resistant Mycobacterium tuberculosis in South Africa. J Antimicrob Chemother. 2009;63:11–16
  90. Giannoni F, Iona E, Sementilli F, Brunori L, Pardini M, Migliori GB, et al. Evaluation of a new line probe assay for rapid identification of gyrA mutations in Mycobacterium tuberculosis. J Clin Microbiol. 2005;49:2928–2933
  91. Kim SY, Park YJ, Song E, et al. Evaluation of the CombiChip Mycobacteria Drug-Resistance detection DNA chip for identifying mutations associated with resistance to isoniazid and rifampin in Mycobacterium tuberculosis. Diagn Microbiol Infect Dis. 2006;54:203–210
  92. Donald PR, Diacon AH. The early bactericidal activity of anti-tuberculosis drugs: a literature review. Tuberculosis. 2008;88:S75–S83
  93. Fortun J, Martin-Davila P, Navas E, et al. Linezolid for the treatment of multidrug-resistant tuberculosis. J Antimicrob Chemother. 2005;56:180–185
  94. Dietze R, Hadad DJ, McGee B, et al. Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis. Am J Respir Crit Care Med. 2008;178:1180–1185
  95. Espinal MA, Kim SJ, Suarez PG, et al. Standard short-course chemotherapy for drug-resistant tuberculosis. JAMA. 2000;283:2537–2545
  96. Mak A, Thomas A, Sel Granado M, Zalekis R, Mouzafarova N, Menzies D. Influence of multidrug-resistance on tuberculosis treatment outcomes with standardized regimens. Am J Respir Crit Care Med. 2008;178:306–312
  97. Lew W, Pai M, Oxdale O, Martin D, Menzies D. Initial drug resistance and tuberculosis treatment outcomes: systematic review and meta-analysis. Ann Intern Med. 2008;149:123–134
  98. Fischl MA, Daikos GL, Uttamchandani RB, et al. Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli. Ann Intern Med. 1992;117:184–190
  99. Park MM, Davis AL, Schluger NW, Cohen H, Rom WN. Outcome of MDR-TB patients, 1983–1993: prolonged survival with appropriate therapy. Am J Respir Crit Care Med. 1996;153:317–324
  100. Turett GS, Telzak EE, Torian LV, et al. Improved outcomes for patients with multidrug-resistant tuberculosis. Clin Infect Dis. 1995;21:1238–1244
  101. Mukherjee JS, Rich ML, Socci AR, et al. Programmes and principles in treatment of multidrug-resistant tuberculosis. Lancet. 2004;363:474–481
  102. Furin J. The clinical management of drug-resistant tuberculosis. Curr Opin Pulm Med. 2007;13:212–217
  103. Mitnick CD, Appleton SC, Shin SS. Epidemiology and treatment of multidrug-resistant tuberculosis. Semin Respir Crit Care Med. 2008;29:499–524
  104. Harries AD, Boxshall M, Phiri S, Kwanjana J. Providing HIV care for tuberculosis patients in sub-Saharan Africa. Int J Tuberc Lung Dis. 2006;10:1306–1311
  105. Rich ML, Socci AR, Mitnick CD, et al. Representative drug susceptibility patterns for guiding design of retreatment regimens for MDR-TB. Int J Tuberc Lung Dis. 2006;10:290–296
  106. Perkins MD, Smith LM. Facing the crises: improving the diagnosis of tuberculosis in the HIV era. J Infect Dis. 2007;196(Suppl. 1):S15–S27
  107. Leimane V, Riekstina V, Holtz TH, et al. Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study. Lancet. 2005;365:318–326
  108. Saravia JC, Appleton SC, Rich ML, Sarria M, Bayona J, Becerra MC. Retreatment management strategies when first-line tuberculosis therapy fails. Int J Tuberc Lung Dis. 2005;9:421–429
  109. Shin SS, Yagui M, Ascencios L, et al. Scale-up of multidrug-resistant tuberculosis laboratory services, Peru. Emerg Infect Dis. 2008;15:701–708
  110. Holtz TH, Sternberg M, Kammerer S, et al. Time to sputum culture conversion in multidrug-resistant tuberculosis: predictors and relationship to treatment outcome. Ann Intern Med. 2006;144:650–659
  111. Han LL, Sloutsky A, Canales R, et al. Acquisition of drug resistance in multidrug-resistant Mycobacterium tuberculosis during directly observed empiric treatment with standardized regimens. Int J Tuberc Lung Dis. 2005;9:818–821
  112. Dominguez-Castellano A, Muniain MA, Muniain MA, et al. Factors associated with time to sputum smear conversion in active pulmonary tuberculosis. Int J Tuberc Lung Dis. 2003;7:432–438
  113. Shin SS, Pasechnikov AD, Gelmanova IY, et al. Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia. Int J Tuberc Lung Dis. 2006;10:402–408
  114. Riekstina V, Leimane V, Holtz TH, Leimans J, Wells CD. Treatment outcome cohort analysis in an integrated DOTS and DOTS-Plus TB program in Latvia. Int J Tuberc Lung Dis. 2007;11:585–587
  115. Van Deun A, Salim MA, Das AP, Bastian I, Portaels F. Results of a standardised regimen for multidrug-resistant tuberculosis in Bangladesh. Int J Tuberc Lung Dis. 2004;8:560–567
  116. Nathanson E, Lambregts-van Weezenbeek C, Rich ML, et al. Multidrug-resistant tuberculosis management in resource-limited settings. Emerg Infect Dis. 2006;12:1389–1397
  117. Tupasi TE, Gupta R, Quelapio MI, et al. Feasibility and cost-effectiveness of treating multidrug-resistant tuberculosis: a cohort study in the Philippines. PLoS Med. 2006;3:e352
  118. World Health Organization . Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva, Switzerland: WHO; 2006;
  119. Mitchison DA. Antimicrobial therapy of tuberculosis: justification for currently recommended treatment regimens. Semin Respir Crit Care Med. 2004;25:307–315
  120. Connolly LE, Edelstein PH, Ramakrishnan L. Why is long-term therapy required to cure tuberculosis. PLoS Med. 2007;4:e120
  121. Salomon JA, Lloyd-Smith JO, Getz WM, et al. Prospects for advancing tuberculosis control through novel therapies. PLoS Med. 2006;3:e273
  122. Ginsberg AM. Emerging drugs for active tuberculosis. Semin Respir Crit Care Med. 2008;29:552–559
  123. Stover CK, Warrener P, VanDevanter DR, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000;405:962–966
  124. Nueremberger E, Tyagi S, Tasneen T, et al. Powerful bactericidal and sterilizing activity of a regimen containing PA-824, moxifloxacin and pyrazinamide in a murine model of tuberculosis. Antimicrob Agents Chemother. 2008;52:1522–1524
  125. Matsumoto M, Hashizume H, Tomishige T, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med. 2006;3:e466
  126. Manjunatha UH, Boshoff H, Dowd CS, et al. Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 2006;103:431–436
  127. Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science. 2005;307:223–227
  128. Lounis N, Veziris N, Chauffour A, Truffot-Pernot C, Andries K, Jarlier V. Combinations of R207910 with drugs used to treat multidrug-resistant tuberculosis have the potential to shorten treatment duration. Antimicrob Agents Chemother. 2006;50:3543–3547
  129. Protopopova M, Hanrahan C, Nikonenko B, et al. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J Antimicrob Chemother. 2005;56:968–974
  130. Nikonenko BV, Protopopova MN, Samala R, Einck L, Nacy CA. Drug therapy of experimental TB: improved outcome by combining SQ109, a new diamine antibiotic with existing TB drugs. Antimicrob Agents Chemother. 2007;51:1563–1565
  131. Villar R, Vicente E, Solano B, et al. In vitro and in vivo antimycobacterial acitivities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide. J Antimicrob Chemother. 2008;62:547–554
  132. Lilienkampf A, Mao J, Wan B, Wang Y, Franzblau SG, Kozikowski AP. Structure-activity relationships for a series of quinoline-based compounds against replicating and nonreplicating. J Med Chem. 2009;52:2109–2118

PII: S0954-6111(09)00244-3

doi: 10.1016/j.rmed.2009.07.010

Respiratory Medicine
Volume 103, Issue 12 , Pages 1777-1790 , December 2009