, Volume 58, Issue 4, pp 633–661 | Cite as

Treatment and Prevention of Multidrug-Resistant Tuberculosis

  • Ivan BastianEmail author
  • Robert Colebunders
Disease Management


Multidrug-resistant tuberculosis (MDRTB), which is defined as combined resistance to isoniazid and rifampicin, is a ‘man-made’ disease that is caused by improper treatment, inadequate drug supplies or poor patient supervision. Patients with MDRTB face chronic disability and death, and represent an infectious hazard for the community. Cure rates of 96% have been achieved but require prompt recognition of the disease, rapid accurate susceptibility results, and early administration of an individualised re-treatment regimen. Such regimens are usually based on a quinolone and an injectable agent (i.e. an aminoglycoside or capreomycin) supplemented by other ‘second-line’ drugs. This therapy is prolonged (e.g. 24 months), expensive, and has multiple adverse effects.

Prevention of MDRTB is therefore of paramount importance. The World Health Organization (WHO) has recommended a multifaceted programme, known by the acronym DOTS (directly observed therapy, short-course), that promotes effective treatment of drug-susceptible TB as the prime method of limiting drug resistance. DOTS was part of a successful MDRTB control programme in New York City, which also included treatment of prevalent MDRTB cases, streamlined laboratory testing, effective infection control procedures and wider application of screening and preventive therapy (although the optimal chemotherapy for MDRTB infection remains undefined).

Industrialised countries have the resources to treat patients with MDRTB and to mount these extensive control programmes. Unfortunately, MDRTB is also prevalent in Asia, South America and the former Soviet Union. First world countries have a vested interest, as well as a moral responsibility, to assist in controlling MDRTB in these ‘hot spots’.


Tuberculosis Adis International Limited Isoniazid Rifabutin Cycloserine 
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  1. 1.
    Dolin PJ, Raviglione MC, Kochi A. Global tuberculosis incidence and mortality during 1990–2000. Bull World Health Organ 1994; 72: 213–20PubMedGoogle Scholar
  2. 2.
    Raviglione MC, Snider DE, Kochi A. Global epidemiology of tuberculosis: morbidity and mortality of a worldwide epidemic. JAMA 1995; 273: 220–6PubMedCrossRefGoogle Scholar
  3. 3.
    Murray CJL, Styblo K, Rouillon A. Tuberculosis in developing countries: burden, intervention and cost. Bull Int Union Tuberc Lung Dis 1990; 65: 6–24PubMedGoogle Scholar
  4. 4.
    Cantwell MF, Snider DE, Cauthen GM, et al. Epidemiology of tuberculosis in the United States, 1985 through 1992. JAMA 1994; 272: 535–9PubMedCrossRefGoogle Scholar
  5. 5.
    Bhatti N, Law MR, Morris JK, et al. Increasing incidence of tuberculosis in England and Wales: a study of the likely causes. BMJ 1995; 310: 967–9PubMedCrossRefGoogle Scholar
  6. 6.
    Raviglione MC, Rieder HL, Styblo K, et al. Tuberculosis trends in Eastern Europe and the former USSR. Tuber Lung Dis 1994; 75: 400–16PubMedCrossRefGoogle Scholar
  7. 7.
    Raviglione MC, Sudre P, Reider HL, et al. Secular trends in tuberculosis in Western Europe. Bull World Health Organ 1993; 71: 297–306PubMedGoogle Scholar
  8. 8.
    Cohn DL, Bustreo F, Raviglione MC. Drug-resistant tuberculosis: review of the worldwide situation and the WHO/IUATLD global surveillance project. Clin Infect Dis 1997; 24 Suppl. 1: S121–30PubMedCrossRefGoogle Scholar
  9. 9.
    Pablos-Mendez A, Raviglione MC, Laszlo A, et al. Global surveillance for antituberculosis-drug resistance, 1994–1997. N Engl J Med 1998; 338: 1641–9PubMedCrossRefGoogle Scholar
  10. 10.
    Bloch AB, Cauthen GM, Onorato IM, et al. Nationwide survey of drug-resistant tuberculosis in the United States. JAMA 1994; 271: 665–71PubMedCrossRefGoogle Scholar
  11. 11.
    Kaye K, Frieden TR. Tuberculosis control: the relevance of classic principles in an era of acquired immunodeficiency syndrome and multidrug resistance. Epidemiol Rev 1996; 18: 52–63PubMedCrossRefGoogle Scholar
  12. 12.
    Brudney K, Dobkin J. Resurgent tuberculosis in New York City: human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs. Am Rev Respir Dis 1991; 144: 745–9PubMedCrossRefGoogle Scholar
  13. 13.
    Barr RG, Menzies R. The effect of war on tuberculosis. Tuber Lung Dis 1994; 75: 251–9PubMedCrossRefGoogle Scholar
  14. 14.
    Gibson N, Boillot F, Jalloh H. The cost of tuberculosis to patients in Sierra Leone’s war zone. Int J Tuberc Lung Dis 1998; 2: 726–31PubMedGoogle Scholar
  15. 15.
    Spence DPS, Hotchkiss J, Williams CSD, et al. Tuberculosis and poverty. BMJ 1993; 307: 759–61PubMedCrossRefGoogle Scholar
  16. 16.
    Mahmoudi A, Iseman MD. Pitfalls in the care of patients with tuberculosis: common errors and their association with the acquisition of drug resistance. JAMA 1993; 270: 65–8PubMedCrossRefGoogle Scholar
  17. 17.
    Liu Z, Shilkret KL, Finelli L. Initial drug regimens for the treatment of tuberculosis: evaluation of physician prescribing practices in New Jersey, 1994 to 1995. Chest 1998; 113: 1446–51PubMedCrossRefGoogle Scholar
  18. 18.
    Sumartojo E. When tuberculosis treatment fails: a social behavioral account of patient adherence. Am Rev Respir Dis 1993; 147: 1311–20PubMedGoogle Scholar
  19. 19.
    Goble M, Iseman MD, Madsen LA, et al. Treatment of 171 patients with pulmonary tuberculosis resistant to isoniazid and rifampin. N Engl J Med 1993; 328: 527–32PubMedCrossRefGoogle Scholar
  20. 20.
    Crofton J, Chaulet P, Maher D, et al. Guidelines for the management of drug resistant tuberculosis. Geneva: World Health Organization, 1997. Publication no. WHO/TB/96.210Google Scholar
  21. 21.
    Iseman MD, Madsen LA. Drug-resistant tuberculosis. Clin Chest Med 1989; 10: 341–53PubMedGoogle Scholar
  22. 22.
    Pearson ML, Jereb JA, Frieden TR, et al. Nosocomial transmission of multidrug-resistant tuberculosis: a risk to patients and health care workers. Ann Intern Med 1992; 117: 191–6PubMedGoogle Scholar
  23. 23.
    Beck-Sague C, Dooley SW, Hutton MD, et al. Hospital outbreak of multidrug-resistant Mycobacterium. tuberculosis infections: factors in transmission to staff and HIV-infected patients. JAMA 1992; 268: 1280–6PubMedCrossRefGoogle Scholar
  24. 24.
    Reeves R, Blakey D, Snider DE, et al. Transmission of multiple drug-resistant tuberculosis: report of a school and community outbreak. Am J Epidemiol 1981; 113: 423–35Google Scholar
  25. 25.
    Centers for Disease Control. Outbreak of multidrug-resistant tuberculosis — Texas, California and, Pennsylvania. MMWR Morb Mortal Wkly Rep 1990; 39: 369–72Google Scholar
  26. 26.
    Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med 1993; 329: 784–91PubMedCrossRefGoogle Scholar
  27. 27.
    Centers for Disease Control. Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons-Florida and New York, 1988–1991. MMWR Morb Mortal Wkly Rep 1991; 40: 585–91Google Scholar
  28. 28.
    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: 184–90PubMedGoogle Scholar
  29. 29.
    Frieden TR, Fujiwara PI, Washko RM, et al. Tuberculosis in New York City — turning the tide. N Engl J Med 1995; 333: 229–33PubMedCrossRefGoogle Scholar
  30. 30.
    Moore M, Onorato IM, McCray E, et al. Trends in drug-resistant tuberculosis in the United States, 1993–1996. JAMA 1997; 278: 833–7PubMedCrossRefGoogle Scholar
  31. 31.
    Public Health Laboratory Service/Communicable Disease Surveillance Centre. Outbreak of hospital acquired multidrug-resistant tuberculosis. Commun Dis Rep Wkly 1995; 5: 161Google Scholar
  32. 32.
    Moro ML, Gori A, Errante I, et al. An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy. AIDS 1998; 12: 1095–102PubMedCrossRefGoogle Scholar
  33. 33.
    Ritacco V, Di Lonardo M, Reniero A, et al. Nosocomial spread of human immunodeficiency-related multidrug-resistant tuberculosis in Buenos Aires. J Infect Dis 1997; 176: 637–42PubMedCrossRefGoogle Scholar
  34. 34.
    Coninx R, Pfyffer GE, Mathieu C, et al. Drug resistant tuberculosis in prisons in Azerbaijan: case study. BMJ 1988; 316: 1423–5CrossRefGoogle Scholar
  35. 35.
    Gilbert GL. Multidrug-resistant tuberculosis: prevention is better than cure. Med J Aust 1996; 164: 121–4PubMedGoogle Scholar
  36. 36.
    Kochi A, Vareldzis B, Styblo K. Multidrug-resistant tuberculosis and its control. Res Microbiol 1994; 144: 104–10CrossRefGoogle Scholar
  37. 37.
    McDermottW, Muschenheim C, Hadley SJ, et al. Streptomycin in the treatment of tuberculosis in humans. Ann Intern Med 1947; 27: 769–822Google Scholar
  38. 38.
    David HL. Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium. tuberculosis. Appl Microbiol 1970; 20: 810–14PubMedGoogle Scholar
  39. 39.
    Mitchison DA. How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. Int J Tuberc Lung Dis 1998; 2: 10–5PubMedGoogle Scholar
  40. 40.
    Iseman MD, Sbarbaro JA. Short course chemotherapy of tuberculosis. Am Rev Respir Dis 1991; 143: 697–8PubMedGoogle Scholar
  41. 41.
    Hong Kong Chest Service/British Medical Research Council. Controlled trials of 2, 4, and 6 months of pyrazinamide in 6-month, three-times-weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide: results at 30 months. Am Rev Respir Dis 1991; 143: 700–6Google Scholar
  42. 42.
    Combs DL, O’Brien PJ, Geiter LJ. USPHS tuberculosis short-course chemotherapy trial 21: effectiveness, toxicity, and acceptability: the report of final results. Ann Intern Med 1990; 112: 397–406PubMedGoogle Scholar
  43. 43.
    Centers for Disease Control. Initial therapy for tuberculosis in the era of multidrug resistance: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Morb Mortal Wkly Rep 1993; 42(RR-7): 1–8Google Scholar
  44. 44.
    American Thoracic Society/Centers for Disease Control. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994; 149: 1359–74Google Scholar
  45. 45.
    Global Tuberculosis Programme. Treatment of tuberculosis: guidelines for national programmes. 2nd ed. Geneva: World Health Organization, 1997. Publication no. WHO/TB/97.220Google Scholar
  46. 46.
    Chaulk CP, Moore Rice K, Rizzo R, et al. Eleven years of community-based directly observed therapy for tuberculosis. JAMA 1995; 274: 945–51PubMedCrossRefGoogle Scholar
  47. 47.
    Mitchison DA. The origins of DOT. Int J Tuberc Lung Dis 1998; 2: 863–5PubMedGoogle Scholar
  48. 48.
    Weis SE, Slocum PC, Biais FX, et al. The effect of directly observed therapy on the rates of drug resistance and relapse in tuberculosis. N Engl J Med 1994; 330: 1179–84PubMedCrossRefGoogle Scholar
  49. 49.
    Chaulk CP, Kazandjian VA. Directly observed therapy for treatment completion of pulmonary tuberculosis: consensus statement of the Public Health Tuberculosis Guidelines Panel. JAMA 1998; 279: 943–8PubMedCrossRefGoogle Scholar
  50. 50.
    Wardman AG, Knox AJ, Muers MF, et al. Profiles of non-compliance with antituberculous therapy. Br J Dis Chest 1988; 82: 285–9PubMedCrossRefGoogle Scholar
  51. 51.
    Bayer R, Stayton C, Desvarieux M, et al. Directly observed therapy and treatment completion for tuberculosis in the United States: is universal supervised therapy necessary? Am J Public Health 1998; 88: 1052–8PubMedCrossRefGoogle Scholar
  52. 52.
    Tuberculosis programme: framework for effective tuberculosis control. Geneva: World Health Organization, 1994. Publication no. WHO/TB/94.179Google Scholar
  53. 53.
    Murray CJL, DeLonghe E, Chum HJ, et al. Cost effectiveness of chemotherapy for pulmonary tuberculosis in three sub-Saharan African countries. Lancet 1991; 338: 1305–8PubMedCrossRefGoogle Scholar
  54. 54.
    Results of directly observed short-course chemotherapy in 112 842 Chinese patients with smear-positive tuberculosis. Chinese Tuberculosis Control Collaboration. Lancet 1996; 347: 358–62Google Scholar
  55. 55.
    Raviglione MC, Dye C, Schmidt S, et al. Assessment of worldwide tuberculosis control. Lancet 1997; 350: 624–9PubMedCrossRefGoogle Scholar
  56. 56.
    Chaulet P. Compliance with chemotherapy for tuberculosis: responsibilities of the Health Ministry and of physicians. Bull Int Union Tuberc Lung Dis 1990–1991; 66 Suppl.: 33–5PubMedGoogle Scholar
  57. 57.
    Byrd RB, Horn BR, Solomon DA, et al. Treatment of tuberculosis by the nonpulmonary physician. Ann Intern Med 1977; 86: 799–802PubMedGoogle Scholar
  58. 58.
    Bloch AB, Simone PM, McCray E, et al. Preventing multidrug-resistant tuberculosis. JAMA 1996; 275: 487–9PubMedCrossRefGoogle Scholar
  59. 59.
    Wenger PN, Otten J, Breeden A, et al. Control of nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis among healthcare workers and HIV-infected patients. Lancet 1995; 345: 235–40PubMedCrossRefGoogle Scholar
  60. 60.
    Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care facilities, 1994. MMWR Morb Mortal Wkly Rep 1994; 43 (RR-13): 1–132Google Scholar
  61. 61.
    Bates JH, Nardell E. Institutional control measures for tuberculosis in the era of multiple drug resistance: ACCP/ATS consensus conference. Chest 1995; 108: 1690–710CrossRefGoogle Scholar
  62. 62.
    Barnes PF. The influence of epidemiologic factors on drug resistance rates in tuberculosis. Am Rev Respir Dis 1987; 136: 325–8PubMedCrossRefGoogle Scholar
  63. 63.
    Ben-Dov I, Mason GR. Drug-resistant tuberculosis in southern Californian hospitals: trends from 1969 to 1984. Am Rev Respir Dis 1987; 135: 1307–10PubMedGoogle Scholar
  64. 64.
    Riley LW, Arathoon E, Loverde VD. The epidemiologic patterns of drug-resistant Mycobacterium tuberculosis infections. Am Rev Respir Dis 1989; 139: 1282–5PubMedGoogle Scholar
  65. 65.
    Telzak EE, Sepkowitz K, Alpert P, et al. Multidrug-resistant tuberculosis in patients without HIV infection. N Engl J Med 1995; 333: 907–11PubMedCrossRefGoogle Scholar
  66. 66.
    Salomon N, Permian DC, Friedmann P, et al. Predictors and outcome of multidrug-resistant tuberculosis. Clin Infect Dis 1995; 21: 1245–52PubMedCrossRefGoogle Scholar
  67. 67.
    Daley CL, Small PM, Schecter GF, et al. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus: an analysis using restriction-fragment-length polymorphisms. N Engl J Med 1992; 326: 231–5PubMedCrossRefGoogle Scholar
  68. 68.
    Centers for Disease Control and Prevention. Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. MMWR Morb Mortal Wkly Rep 1998; 47(RR-20): 1–58Google Scholar
  69. 69.
    Park MM, Davis AL, Schluger NW, et al. Outcome of MDR-TB patients, 1983–1993: prolonged survival with appropriate therapy. Am J Respir Crit Care Med 1996; 153: 317–24PubMedGoogle Scholar
  70. 70.
    Mannheimer SB, Sepkowitz KA, Stoeckle M, et al. Risk factors and outcome of human immunodeficiency virus-infected patients with sporadic multi drug-resistant tuberculosis in New York City. Int J Tuberc Lung Dis 1997; 1: 319–25PubMedGoogle Scholar
  71. 71.
    Kim TC, Blackman RS, Heatwole KM, et al. Acid-fast bacilli in sputum smears of patients with pulmonary tuberculosis. Prevalence and significance of negative smears pretreatment and positive smears post-treatment. Am Rev Respir Dis 1984; 129: 264–8PubMedGoogle Scholar
  72. 72.
    Tenover FC, Crawford JT, Huebner RE, et al. The resurgence of tuberculosis: is your laboratory ready? J Clin Microbiol 1993; 31: 767–70PubMedGoogle Scholar
  73. 73.
    Huebner RE, Good RC, Tokars JI. Current practices in mycobacteriology: results of a survey of state public health laboratories. J Clin Microbiol 1993; 31: 771–5PubMedGoogle Scholar
  74. 74.
    Inderlied CB, Salfinger M. Antimicrobial agents and susceptibilty tests: mycobacteria. In: Murray PR, Baron EJ, Pfaller MA, et al, editors. Manual of clinical microbiology. 6th ed. Washington, D.C.: American Society for Microbiology, 1995: 1385–404Google Scholar
  75. 75.
    Anargyros P, Astill DSJ, Lim ISL. Comparison of improved B ACTEC and Lowenstein-Jensen media for culture of mycobacteria from clinical specimens. J Clin Microbiol 1990; 28: 1288–91PubMedGoogle Scholar
  76. 76.
    Garza-Gonzalez E, Guerrero-Olazaran M, Tijerina-Mechaca, et al. Determination of drug susceptibility of Mycobacterium tuberculosis through mycolic acid analysis. J Clin Microbiol 1997; 35: 1287–9PubMedGoogle Scholar
  77. 77.
    Heifets L, Cangelosi GA. Drug susceptibility testing of Mycobacterium tuberculosis — a neglected problem at the turn of the century. Int J Tuberc Lung Dis 1999; 3: 564–81PubMedGoogle Scholar
  78. 78.
    Rieder HL. Sputum smear conversion during directly observed treatment for tuberculosis. Tuber Lung Dis 1996; 77: 124–9PubMedCrossRefGoogle Scholar
  79. 79.
    Kritski AL, Rodrigues de Jesus LS, Andrade MK, et al. Retreatment tuberculosis cases: factors associated with drug resistance and adverse outcomes. Chest 1997; 111: 1162–7PubMedCrossRefGoogle Scholar
  80. 80.
    Crofton J. The prevention and management of drug-resistant tuberculosis. Bull Int Union Tuberc Lung Dis 1987; 62: 6–11PubMedGoogle Scholar
  81. 81.
    Harkin TJ, Harris HW. Treatment of multidrug-resistant tuberculosis. In: Rom WN, Gray SM, editors. Tuberculosis. New York: Little, Brown & Company (Inc.), 1996: 843–50Google Scholar
  82. 82.
    Davidson PT, Le HQ. Drug treatment of tuberculosis — 1992. Drugs 1992; 43: 651–73PubMedCrossRefGoogle Scholar
  83. 83.
    McClatchy JK, Kanes W, Davidson PT, et al. Cross-resistance in M. tuberculosis to kanamycin, capreomycin and viomycin. Tubercle 1977; 58: 29–34PubMedCrossRefGoogle Scholar
  84. 84.
    Peloquin CA. Pharmacology of the antimycobacterial drugs. Med Clin North Am 1993; 77: 1253–62PubMedGoogle Scholar
  85. 85.
    Aranda CP. Second-line agents: p-aminosalicylic acid, ethionamide, cycloserine, and thiacetazone. In: Rom WN, Gray SM, editors. Tuberculosis. New York: Little,Brown & Company (Inc.), 1996:811–6Google Scholar
  86. 86.
    Ji B, Lounis N, Masio C, et al. In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998; 42: 2066–9PubMedGoogle Scholar
  87. 87.
    Saito H, Sato K, Tomioka H, et al. In vitro antimycobacterial activity of a new quinolone, levofloxacin (DR-3355). Tuber Lung Dis 1995; 76: 377–80PubMedCrossRefGoogle Scholar
  88. 88.
    Garcia-Rodriguez JA, Gomez Garcia AC. In vitro activities of quinolones against mycobacteria. J Antimicrob Chemother 1993; 32: 797–808PubMedCrossRefGoogle Scholar
  89. 89.
    Alangaden GJ, Lerner SA. The clinical use of the fluoro-quinolones for the treatment of mycobacterial diseases. Clin Infect Dis 1997; 25: 1213–21PubMedCrossRefGoogle Scholar
  90. 90.
    Kennedy N, Berger L, Curram J, et al. Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis. Clin Infect Dis 1996; 22: 827–33PubMedCrossRefGoogle Scholar
  91. 91.
    Sirgel FA, Botha FJ, Parkin DP, et al. The early bactericidal activity of ciprofloxacin in patients with pulmonary tuberculosis. Am J Respir Crit Care Med 1997; 156: 901–5PubMedGoogle Scholar
  92. 92.
    Tsukamura M, Nakamura E, Yoshi S, et al. Therapeutic effect of a new antibacterial substance ofloxacin (DL8280) on pulmonary tuberculosis. Am Rev Respir Dis 1985; 131: 352–6PubMedGoogle Scholar
  93. 93.
    Yew WW, Kwan SY, Ma WK, et al. In vitro activity of ofloxacin against Mycobacterium tuberculosis and its clinical efficacy in multiply resistant pulmonary tuberculosis. J Antimicrob Chemother 1990; 26: 227–36PubMedCrossRefGoogle Scholar
  94. 94.
    Hong Kong Chest Service/British Medical Research Council. A controlled study of rifabutin and an uncontrolled study of ofloxacin in the retreatment of patients with pulmonary tuberculosis resistant to isoniazid, streptomycin and rifampicin. Tuber Lung Dis 1992; 73: 59–67CrossRefGoogle Scholar
  95. 95.
    Sullivan EA, Kreiswirth BN, Palumbo L, et al. Emergence of fluoroquinolone-resistant tuberculosis in New York City. Lancet 1995; 345: 1148–50PubMedCrossRefGoogle Scholar
  96. 96.
    Xu C, Kreiswirth BN, Sreevatsan S, et al. Fluoroquinolone resistance associated with specific gyrase mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis. J Infect Dis 1996; 174: 1127–30PubMedCrossRefGoogle Scholar
  97. 97.
    Kaplan JA, Krieff DM. Quinolones for the treatment and prophylaxis of tuberculosis. Ann Pharmacother 1996; 30: 1020–2PubMedGoogle Scholar
  98. 98.
    Berning SE, Madsen L, Iseman MD, et al. Long-term safety of ofloxacin and ciprofloxacin in the treatment of mycobacterial infections. Am J Respir Crit Care Med 1995; 151: 2006–9PubMedGoogle Scholar
  99. 99.
    Berning SE, Huitt GA, Iseman MD, et al. Malabsorption of antituberculosis medications by a patient with AIDS. N Engl J Med 1992; 327: 1817–8PubMedCrossRefGoogle Scholar
  100. 100.
    Iseman MD, Madsen L, Goble M, et al. Surgical intervention in the treatment of pulmonary disease caused by drug-resistant Mycobacterium tuberculosis. Am Rev Respir Dis 1990; 141: 623–5PubMedCrossRefGoogle Scholar
  101. 101.
    Muthuswamy P, Chechani V, Barker W. Surgical management of pulmonary tuberculosis [abstract]. Am Rev Respir Dis 1992; 145: A816Google Scholar
  102. 102.
    Pomerantz M, Brown JM. Surgery in the treatment of multi-drug-resistant tuberculosis. Clin Chest Med 1997; 18: 123–30PubMedCrossRefGoogle Scholar
  103. 103.
    Mitchison DA, Nunn AJ. Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis. Am Rev Respir Dis 1986; 133: 423–30PubMedGoogle Scholar
  104. 104.
    Frieden TR, Sherman LF, Maw KL, et al. A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes. JAMA 1996; 276: 1229–35PubMedCrossRefGoogle Scholar
  105. 105.
    Carpels G, Fissette K, Limbana V, et al. Drug resistant tuberculosis in sub Saharan Africa: an estimation of incidence and cost for the year 2000. Tuber Lung Dis 1995; 76: 480–6PubMedCrossRefGoogle Scholar
  106. 106.
    Blumberg UM, Watkins DL, Berschling JD, et al. Preventing the nosocomial transmission of tuberculosis. Ann Intern Med 1995; 122: 658–63PubMedGoogle Scholar
  107. 107.
    Maloney SA, Pearson ML, Gordon MT, et al. Efficacy of control measures in preventing nosocomial transmission of multi-drug-resistant tuberculosis to patients and health care workers. Ann Intern Med 1995; 122: 90–5PubMedGoogle Scholar
  108. 108.
    Adal KA, Anglim AM, Palumbo CL, et al. The use of high-efficiency particulate air-filter respirators to protect hospital workers from tuberculosis: a costeffectiveness analysis. N Engl J Med 1994; 331: 169–73PubMedCrossRefGoogle Scholar
  109. 109.
    Centers for Disease Control. The use of preventative therapy for tuberculous infection in the United States: recommendations of the Advisory Committee for Elimination of Tuberculosis. MMWR Morb Mortal Wkly Rep 1990; 39(RR-8): 9–12Google Scholar
  110. 110.
    International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventative therapy for tuberculosis: 5 years of follow-up in the IUAT trial. Bull World Health Organ 1982; 60: 555–64Google Scholar
  111. 111.
    Snider DE, Caras GJ, Koplan JP. Preventative therapy with isoniazid: cost-effectiveness of different durations of therapy. JAMA 1986; 255: 1579–83PubMedCrossRefGoogle Scholar
  112. 112.
    O’Brien RJ, Perriens JH. Preventative therapy for tuberculosis in HIV infection: the promise and the reality. AIDS 1995; 9: 665–73PubMedCrossRefGoogle Scholar
  113. 113.
    World Health Organization/International Union Against Tuberculosis and Lung Disease. Tuberculosis preventative therapy in HIV-infected individuals: a joint statement of the WHO Tuberculosis Programme and the Global Programme on AIDS, and the International Union Against Tuberculosis and Lung Disease (IUATLD). Wkly Epidemiol Rec 1993; 68: 361–8Google Scholar
  114. 114.
    Koplan JP, Farer LS. Choice of preventative treatment for isoniazid-resistant tuberculous infection. JAMA 1980; 244: 2736–40PubMedCrossRefGoogle Scholar
  115. 115.
    Villarino ME, Ridzon R, Weismuller PC, et al. Rifampin preventive therapy for tuberculosis infection: experience with 157 adolescents. Am J Respir Crit Care Med 1997; 155: 1735–8PubMedGoogle Scholar
  116. 116.
    Polesky A, Farber HW, Gottlieb DJ, et al. Rifampin preventive therapy for tuberculosis in Boston’s homeless. Am J Respir Crit Care Med 1996; 154: 1473–7PubMedGoogle Scholar
  117. 117.
    Centers for Disease Control. Management of persons exposed to multidrug-resistant tuberculosis. MMWR Morb Mortal Wkly Rep 1992; 41(RR-11): 61–71Google Scholar
  118. 118.
    Passannante MR, Gallagher CT, Reichman LB. Preventative therapy for contacts of multidrug-resistant tuberculosis: a Delphi survey. Chest 1994; 106: 431–4PubMedCrossRefGoogle Scholar
  119. 119.
    Stevens JP, Daniel TM. Chemoprophylaxis of multidrug-resistant tuberculous infection in HIV-uninfected individuals using ciprofloxacin and pyrazinamide: a decision analysis. Chest 1995; 108: 712–7PubMedCrossRefGoogle Scholar
  120. 120.
    Horn DL, Hewlett D, Alfalla C, et al. Limited tolerance of ofloxacin and pyrazinamide prophylaxis against tuberculosis. N Engl J Med 1994; 330: 1241PubMedCrossRefGoogle Scholar
  121. 121.
    Villarino ME, Simone PM, McCray E, et al. Preventive therapy for multidrug-resistant tuberculosis. JAMA 1996; 276: 28CrossRefGoogle Scholar
  122. 122.
    Brewer TF, Colditz GA. Bacille Calmette-Guerin vaccination for the prevention of tuberculosis in health care workers. Clin Infect Dis 1995; 20: 136–42PubMedCrossRefGoogle Scholar
  123. 123.
    Stevens JP, Daniel TM. Bacille Calmette-Guerin immunization of healthcare workers exposed to multidrug-resistant tuberculosis: a decision analysis. Tuber Lung Dis 1996; 77: 315–21PubMedCrossRefGoogle Scholar
  124. 124.
    Jenney AWJ, Spelman DW. In support of Bacillus of Calmette and Guerin for healthcare workers. Infect Control Hosp Epidemiol 1998; 19: 191–3PubMedCrossRefGoogle Scholar
  125. 125.
    Colditz GA, Brewer TF, Berkey CS, et al. Efficacy of BCG vaccine in the prevention of tuberculosis: meta-analysis of the published literature. JAMA 1994; 271: 698–702PubMedCrossRefGoogle Scholar
  126. 126.
    Centers for Disease Control. The role of BCG vaccine in the prevention and control of tuberculosis in the United States. MMWR Morb Mortal Wkly Rep 1996; 45(RR-4): 1–18Google Scholar
  127. 127.
    O’Brien RJ, Vernon AA. New tuberculosis drug development. How can we do better? Am Rev Respir Crit Care Med 1998; 157: 1705–7Google Scholar
  128. 128.
    Moulding TS. Should isoniazid be used in retreatment of tuberculosis despite acquired isoniazid resistance. Am Rev Respir Dis 1981; 123: 262–4PubMedGoogle Scholar
  129. 129.
    Victor TC, Warren R, Butt JL, et al. Genome and MIC stability in Mycobacterium tuberculosis and indications for continuation of use of isoniazid in multidrug-resistant tuberculosis. J Med Microbiol 1997; 46: 847–57PubMedCrossRefGoogle Scholar
  130. 130.
    Klemens SP, DeStefano MS, Cynamon MH. Therapy of multidrug-resistant tuberculosis: lessons from studies with mice. Antimicrob Agents Chemother 1993; 37: 2344–7PubMedCrossRefGoogle Scholar
  131. 131.
    De Cian W, Sassella D, Wynne BA. Clinical experience with rifabutin in the treatment of mycobacterial infections. Scand J Infect Dis 1995; Suppl. 98: 22–6Google Scholar
  132. 132.
    Heifets LB, Lindholm-Levy PJ, Iseman MD. Rifabutine: minimal inhibitory and bactericidal concentrations for Mycobacterium tuberculosis. Am Rev Respir Dis 1988; 137: 719–21PubMedGoogle Scholar
  133. 133.
    Gonzalez-Montaner LJ, Natal S, Yongchaiyud P, et al. Rifabutin for the treatment of newly-diagnosed pulmonary tuberculosis: a multinational, randomized, comparative study versus rifampicin. Tuber Lung Dis 1994; 75: 341–7PubMedCrossRefGoogle Scholar
  134. 134.
    McGregor MM, Olliaro P, Wolmarans L, et al. Efficacy and safety of rifabutin in the treatment of patients with newly diagnosed pulmonary tuberculosis. Am J Respir Crit Care Med 1996; 154: 1462–7PubMedGoogle Scholar
  135. 135.
    Grassi C, Peona V. Use of rifabutin in the treatment of pulmonary tuberculosis. Clin Infect Dis 1996; 22 Suppl. 1: S50–4PubMedCrossRefGoogle Scholar
  136. 136.
    Hardy DJ, Guay DRP, Jones RN. Clarithromycin, a unique macrolide: a pharmacokinetic, microbiological, and clinical overview. Diagn Microbiol Infect Dis 1992; 15: 39–53PubMedCrossRefGoogle Scholar
  137. 137.
    Hoffner SE, Gezelius L, Olsson-Liljequist B. In vitro activity of fluorinated quinolones and macrolides against drug-resistant Mycobacterium tuberculosis. J Antimicrob Chemother 1997; 40: 885–8PubMedCrossRefGoogle Scholar
  138. 138.
    Luna-Herrera J, Reddy VM, Daneluzzi D, et al. Antituberculosis activity of clarithromycin. Antimicrob Agents Chemother 1995; 39: 2692–5PubMedCrossRefGoogle Scholar
  139. 139.
    Truffot-Pernot C, Lounis N, Grosset JH, et al. Clarithromycin is inactive against Mycobacterium tuberculosis. Antimicrob Agents Chemother 1995; 39: 2827–8PubMedCrossRefGoogle Scholar
  140. 140.
    Cavalieri SJ, Biehle JR, Sanders WE. Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 1995; 39: 1542–5PubMedCrossRefGoogle Scholar
  141. 141.
    Jagannath C, Reddy VM, Kailasam S, et al. Chemotherapeutic activity of clofazimine and its analogues against Mycobacterium tuberculosis: in vitro, intracellular, and in vivo studies. Am J Respir Crit Care Med 1995; 151: 1083–6PubMedGoogle Scholar
  142. 142.
    Reddy VM, Nadadhur G, Daneluzzi D, et al. Antituberculosis activities of clofazimine and its new analogs B4154 and B4157. Antimicrob Agents Chemother 1996; 40: 633–6PubMedGoogle Scholar
  143. 143.
    Shah A, Bhagat R, Panchal N. Resistant tuberculosis: successful treatment with amikacin, ofloxacin, clofazimine and PAS. Tuber Lung Dis 1993; 74: 64–7PubMedCrossRefGoogle Scholar
  144. 144.
    Chambers HF, Moreau D, Yajko D, et al. Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis? Antimicrob Agents Chemother 1995; 39: 2620–4PubMedCrossRefGoogle Scholar
  145. 145.
    Voladri RKR, Lakey DL, Hennigan SH, et al. Recombinant expression and characterization of the major β-lactamase of Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998; 42: 1375–81PubMedGoogle Scholar
  146. 146.
    Cynamon MH, Palmer GS. In vitro activity of amoxicillin in combination with clavulanic acid against Mycobacterium tuberculosis. Antimicrob Agents Chemother 1983; 24: 429–31PubMedCrossRefGoogle Scholar
  147. 147.
    Nadler JP, Berger J, Nord JA, et al. Amoxicillin-clavulanic acid for treating drug-resistant Mycobacterium tuberculosis. Chest 1991; 99: 1025–6PubMedCrossRefGoogle Scholar
  148. 148.
    Yew WW, Wong CF, Lee J, et al. Do β-lactam-β-lactamase inhibitor combinations have a place in the treatment of multi-drug-resistant pulmonary tuberculosis. Tuber Lung Dis 1995; 76: 90–2PubMedCrossRefGoogle Scholar
  149. 149.
    Chambers HF, Kocagoz T, Sipit T, et al. Activity of amoxicillin/clavulanate in patients with tuberculosis. Clin Infect Dis 1998; 26: 874–7PubMedCrossRefGoogle Scholar
  150. 150.
    Wayne LG. Dormancy of Mycobacterium tuberculosis and latency of disease. Eur J Clin Microbiol Infect Dis 1994; 13: 908–14PubMedCrossRefGoogle Scholar
  151. 151.
    Wayne LG, Sramek HA. Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis. Antimicrob Agents Chemother 1994; 38: 2054–8PubMedCrossRefGoogle Scholar
  152. 152.
    Dhillon J, Alien BW, Hu Y-M, et al. Metronidazole has no antibacterial effect in Cornell model murine tuberculosis. Int J Tuberc Lung Dis 1998; 2: 736–42PubMedGoogle Scholar
  153. 153.
    Oleksijew A, Meulbroek J, Ewing P, et al. In vivo efficacy of ABT-255 against drug-sensitive and drug-resistant Mycobacterium tuberculosis strains. Antimicrob Agents Chemother 1998; 42: 2674–7PubMedGoogle Scholar
  154. 154.
    Grandoni JA, Marta PT, Schloss JV. Inhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents. J Antimicrob Chemother 1998; 42: 475–82PubMedCrossRefGoogle Scholar
  155. 155.
    Amaral L, Kristiansen JE, Abebe LS, et al. Inhibition of the respiration of multidrug-resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: potential use for initial therapy of freshly diagnosed tuberculosis. J Antimicrob Chemother 1996; 38: 1049–53PubMedCrossRefGoogle Scholar
  156. 156.
    Condos R, Rom WN, Schluger NW. Treatment of multidrug-resistant pulmonary tuberculosis with interferon-gamma via aerosol. Lancet 1997; 349: 1513–5PubMedCrossRefGoogle Scholar
  157. 157.
    Prior JG, Khan AA, Cartwright KAV, et al. Immunotherapy with Mycobacterium vaccae combined with second line chemotherapy in drug-resistant abdominal tuberculosis. J Infection 1995; 31: 59–61CrossRefGoogle Scholar
  158. 158.
    Rom WN, Yie T-A, Tchou-Wong K-M. Development of a suicide gene as a novel approach to killing Mycobacterium tuberculosis. Am J Respir Crit Care Med 1997; 156: 1993–8PubMedGoogle Scholar
  159. 159.
    Farmer P, Kim JY. Community based approaches to the control of multidrug-resistant tuberculosis: introducing “DOTS-plus”. BMJ 1998; 317: 671–4PubMedCrossRefGoogle Scholar
  160. 160.
    Fujiwara PI, Larkin C, Frieden TR. Directly observed therapy in New York City: history, implementation, results and challenges. Clin Chest Med 1997; 18: 135–48PubMedCrossRefGoogle Scholar
  161. 161.
    Kim SJ, Hong YP. Drug resistance of Mycobacterium tuberculosis in Korea. Tuber Lung Dis 1992; 73: 219–24PubMedCrossRefGoogle Scholar
  162. 162.
    Kim SJ, Bai GH, Hong YP. Drug-resistant tuberculosis in Korea, 1994. Int J Tuberc Lung Dis 1997; 1: 302–8PubMedGoogle Scholar
  163. 163.
    Boulahbal F, Khaled S, Tazir M. The interest of follow-up of resistance of the tubercle bacillus in the evaluation of a programme. Bull Int Union Tuberc Lung Dis 1989; 64(3): 23–5PubMedGoogle Scholar
  164. 164.
    Styblo K, Dankova D, Drapela J, et al. Epidemiological and clinical study of tuberculosis in the district of Kolin, Czechoslovakia: report for the first 4 years of the study (1961–64). Bull World Health Organ 1967; 37: 819–74PubMedGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  1. 1.Institute of Tropical MedicineAntwerpenBelgium

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