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Semin Respir Crit Care Med 2013; 34(01): 044-059
DOI: 10.1055/s-0032-1333546
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Management of Multidrug Resistant Tuberculosis

Charles L. Daley
1   Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, Colorado
2   Division of Pulmonary and Critical Care Medicine, University of Colorado Denver, Aurora, Colorado
3   Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado
,
Jose A. Caminero
4   Servicio de Neumologia, Hospital General de Gran Canaria, Las Palmas, Canary Islands, Spain
5   MDR-TB Unit, International Union against Tuberculosis and Lung Disease (The Union), Paris, France
› Author Affiliations
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Publication History

Publication Date:
04 March 2013 (online)

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Abstract

Drug-resistant strains of Mycobacterium tuberculosis have emerged as a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment has allowed M. tuberculosis to acquire resistance to our most important antituberculosis drugs. The epidemic of drug-resistant tuberculosis has spread quickly in some areas due to the convergence of resistant strains of M. tuberculosis in high-risk patients (e.g., those with human immunodeficiency virus/acquired immunodeficiency syndrome) and high-risk environments (e.g., hospitals and prisons). The World Health Organization (WHO) estimates that there were 650,000 cases of multidrug resistant tuberculosis (MDR-TB) in 2010, defined as strains that are resistant to at least isoniazid (INH) and rifampicin (RIF). Globally, WHO estimates that 3.7% of new tuberculosis cases and 20% of re-treatment cases have MDR-TB. By the end of 2012, 84 countries had reported at least one case of extensively drug resistant strains (XDR-TB), which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. Recently, cases of “totally drug resistant” tuberculosis have been reported. It is estimated that only 10% of all MDR-TB cases are currently receiving therapy and only 2% are receiving quality-assured drugs. This article reviews the management of MDR and XDR-TB and highlights the updated 2011 WHO guidelines on the programmatic management of drug-resistant tuberculosis.

Keywords

tuberculosis - drug resistant - MDR-TB - XDR-TB - management
 

  • References

  • 1 Global Tuberculosis Control, WHO. WHO Report 2011. Geneva, Switzerland: World Health Organization; 2011
    Google Scholar
  • 2 WHO. Global Tuberculosis Report 2012. Geneva, Switzerland: WHO; 2012
    Google Scholar
  • 3 Migliori GB, De Iaco G, Besozzi G, Centis R, Cirillo DM. First tuberculosis cases in Italy resistant to all tested drugs. Euro Surveill 2007; 12 (5) E070517.1
    PubMedGoogle Scholar
  • 4 Velayati AA, Masjedi MR, Farnia P , et al. Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran. Chest 2009; 136 (2) 420-425
    CrossrefPubMedGoogle Scholar
  • 5 Udwadia ZF, Amale RA, Ajbani KK, Rodrigues C. Totally drug-resistant tuberculosis in India. Clin Infect Dis 2012; 54 (4) 579-581
    CrossrefPubMedGoogle Scholar
  • 6 Boehme CC, Nabeta P, Hillemann D , et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 2010; 363 (11) 1005-1015
    CrossrefPubMedGoogle Scholar
  • 7 Hillemann D, Rüsch-Gerdes S, Richter E. Evaluation of the GenoTypeMTBDRplus assay for rifampin and isoniazid susceptibility testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol 2007; 45 (8) 2635-2640
    CrossrefPubMedGoogle Scholar
  • 8 WHO. Towards Universal Access to Diagnosis and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis by 2015. WHO Progress Report 2011. Geneva, Switzerland: World Health Organization; 2011
    Google Scholar
  • 9 WHO. Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis. 2011 Update. Geneva, Switzerland: World Health Organization; 2011
    Google Scholar
  • 10 WHO. Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis. Emergency Update 2008. Geneva, Switzerland: World Health Organization; 2008
    Google Scholar
  • 11 Orenstein EW, Basu S, Shah NS , et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis 2009; 9 (3) 153-161
    CrossrefPubMedGoogle Scholar
  • 12 WHO. Treatment of Tuberculosis: Guidelines for National Programmes. 4th ed. Geneva, Switzerland: World Health Organization. 2010. http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf . Accessed July 30, 2010
    PubMedGoogle Scholar
  • 13 Dooley KE, Mitnick CD, Ann DeGroote M , et al; Efficacy Subgroup, RESIST-TB. Old drugs, new purpose: retooling existing drugs for optimized treatment of resistant tuberculosis. Clin Infect Dis 2012; 55 (4) 572-581
    CrossrefPubMedGoogle Scholar
  • 14 Gagneux S, Burgos MV, DeRiemer K , et al. Impact of bacterial genetics on the transmission of isoniazid-resistant Mycobacterium tuberculosis. PLoS Pathog 2006; 2 (6) e61
    CrossrefPubMedGoogle Scholar
  • 15 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 (12) 3799-3805
    CrossrefPubMedGoogle Scholar
  • 16 Banerjee A, Dubnau E, Quemard A , et al. inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis. Science 1994; 263 (5144) 227-230
    CrossrefPubMedGoogle Scholar
  • 17 Caminero JA, Sotgiu G, Zumla A, Migliori GB. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis 2010; 10 (9) 621-629
    CrossrefPubMedGoogle Scholar
  • 18 Warren RM, Streicher EM, Gey van Pittius NC , et al. The clinical relevance of Mycobacterial pharmacogenetics. Tuberculosis (Edinb) 2009; 89 (3) 199-202
    CrossrefPubMedGoogle Scholar
  • 19 Müller B, Streicher EM, Hoek KG , et al. inhA promoter mutations: a gateway to extensively drug-resistant tuberculosis in South Africa?. Int J Tuberc Lung Dis 2011; 15 (3) 344-351
    PubMedGoogle Scholar
  • 20 Cynamon MH, Zhang Y, Harpster T, Cheng S, DeStefano MS. High-dose isoniazid therapy for isoniazid-resistant murine Mycobacterium tuberculosis infection. Antimicrob Agents Chemother 1999; 43 (12) 2922-2924
    PubMedGoogle Scholar
  • 21 Katiyar SK, Bihari S, Prakash S, Mamtani M, Kulkarni H. A randomized controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 2008; 12: 129-145
    PubMedGoogle Scholar
  • 22 Schaaf HS, Moll AP, Dheda K. Multidrug- and extensively drug-resistant tuberculosis in Africa and South America: epidemiology, diagnosis and management in adults and children. Clin Chest Med 2009; 30 (4) 667-683 , vii–viii
    CrossrefPubMedGoogle Scholar
  • 23 Van Deun A, Maug AK, Salim MA , et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 2010; 182 (5) 684-692
    CrossrefPubMedGoogle Scholar
  • 24 Zhang Y, Telente A. Genetics of drug resistance in Mycobacterium tuberculosis. In: Hatfull GF, Jacobs Jr WR, , eds. Molecular Genetics of Mycobacteria. Washington, DC: ASM Press; 2000: 235-254
    Google Scholar
  • 25 Williams DL, Spring L, Collins L , et al. Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998; 42 (7) 1853-1857
    PubMedGoogle Scholar
  • 26 Sintchenko V, Chew WK, Jelfs PJ, Gilbert GL. Mutations in rpoB gene and rifabutin susceptibility of multidrug-resistant Mycobacterium tuberculosis strains isolated in Australia. Pathology 1999; 31 (3) 257-260
    CrossrefPubMedGoogle Scholar
  • 27 Uzun M, Erturan Z, Anğ O. Investigation of cross-resistance between rifampin and rifabutin in Mycobacterium tuberculosis complex strains. Int J Tuberc Lung Dis 2002; 6 (2) 164-165
    PubMedGoogle Scholar
  • 28 Cavusoglu C, Hilmioglu S, Guneri S, Bilgic A. Characterization of rpoB mutations in rifampin-resistant clinical isolates of Mycobacterium tuberculosis from Turkey by DNA sequencing and line probe assay. J Clin Microbiol 2002; 40 (12) 4435-4438
    CrossrefPubMedGoogle Scholar
  • 29 Yoshida S, Suzuki K, Iwamoto T , et al. Comparison of rifabutin susceptibility and rpoB mutations in multi-drug-resistant Mycobacterium tuberculosis strains by DNA sequencing and the line probe assay. J Infect Chemother 2010; 16 (5) 360-363
    CrossrefPubMedGoogle Scholar
  • 30 Shi W, Zhang X, Jiang X , et al. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science 2011; 333 (6049) 1630-1632
    CrossrefPubMedGoogle Scholar
  • 31 Tousek J, Jancik E, Zelenka M, Jancikova-Máková M. The results of treatment in patients with cultures resistant to streptomycin, isoniazid and PAS: a five-year follow-up. Tubercle 1967; 48 (1) 27-31
    CrossrefPubMedGoogle Scholar
  • 32 Zierski M, Zachara A. Late results in re-treatment of patients with pulmonary tuberculosis. Tubercle 1970; 51 (2) 172-177
    CrossrefPubMedGoogle Scholar
  • 33 Somner AR, Brace AA. Late results of treatment of chronic drug-resistant pulmonary tuberculosis. BMJ 1966; 1 (5490) 775-778
    CrossrefPubMedGoogle Scholar
  • 34 Mitnick C, Bayona J, Palacios E , et al. Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. N Engl J Med 2003; 348 (2) 119-128
    CrossrefPubMedGoogle Scholar
  • 35 Migliori GB, Besozzi G, Girardi E , et al; SMIRA/TBNET Study Group. Clinical and operational value of the extensively drug-resistant tuberculosis definition. Eur Respir J 2007; 30 (4) 623-626
    CrossrefPubMedGoogle Scholar
  • 36 Crowle AJ, Sbarbaro JA, Judson FN, Douvas GS, May MH. Inhibition by streptomycin of tubercle bacilli within cultured human macrophages. Am Rev Respir Dis 1984; 130 (5) 839-844
    PubMedGoogle Scholar
  • 37 Caminero JA. World Health Organization; American Thoracic Society; British Thoracic Society. Treatment of multidrug-resistant tuberculosis: evidence and controversies. Int J Tuberc Lung Dis 2006; 10 (8) 829-837
    PubMedGoogle Scholar
  • 38 Heifets L, Lindholm-Levy P. Comparison of bactericidal activities of streptomycin, amikacin, kanamycin, and capreomycin against Mycobacterium avium and M. tuberculosis. Antimicrob Agents Chemother 1989; 33 (8) 1298-1301
    CrossrefPubMedGoogle Scholar
  • 39 Alangaden GJ, Kreiswirth BN, Aouad A , et al. Mechanism of resistance to amikacin and kanamycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998; 42 (5) 1295-1297
    PubMedGoogle Scholar
  • 40 Krüüner A, Jureen P, Levina K, Ghebremichael S, Hoffner S. Discordant resistance to kanamycin and amikacin in drug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 2003; 47 (9) 2971-2973
    CrossrefPubMedGoogle Scholar
  • 41 Maus CE, Plikaytis BB, Shinnick TM. Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2005; 49 (8) 3192-3197
    CrossrefPubMedGoogle Scholar
  • 42 Georghiou SB, Magana M, Garfein RS, Catanzaro DG, Catanzaro A, Rodwell TC. Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review. PLoS ONE 2012; 7 (3) e33275
    CrossrefPubMedGoogle Scholar
  • 43 Migliori GB, Lange C, Girardi E , et al; SMIRA/TBNET Study Group. Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis?. Eur Respir J 2008; 31 (4) 904-905
    CrossrefPubMedGoogle Scholar
  • 44 Chan ED, Laurel V, Strand MJ , et al. Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis. Am J Respir Crit Care Med 2004; 169 (10) 1103-1109
    CrossrefPubMedGoogle Scholar
  • 45 Chiang CY, Enarson DA, Yu MC , et al. Outcome of pulmonary multidrug-resistant tuberculosis: a 6-yr follow-up study. Eur Respir J 2006; 28 (5) 980-985
    CrossrefPubMedGoogle Scholar
  • 46 Ziganshina LE, Squire SB. Fluoroquinolones for treating tuberculosis. Cochrane Database Syst Rev 2008; (1) CD004795
    PubMedGoogle Scholar
  • 47 Ginsburg AS, Grosset JH, Bishai WR. Fluoroquinolones, tuberculosis, and resistance. Lancet Infect Dis 2003; 3 (7) 432-442
    CrossrefPubMedGoogle Scholar
  • 48 Yew WW, Chan CK, Leung CC , et al. Comparative roles of levofloxacin and ofloxacin in the treatment of multidrug-resistant tuberculosis: preliminary results of a retrospective study from Hong Kong. Chest 2003; 124 (4) 1476-1481
    CrossrefPubMedGoogle Scholar
  • 49 Johnson JL, Hadad DJ, Boom WH , et al. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis 2006; 10 (6) 605-612
    PubMedGoogle Scholar
  • 50 Peloquin CA, Hadad DJ, Molino LP , et al. Population pharmacokinetics of levofloxacin, gatifloxacin, and moxifloxacin in adults with pulmonary tuberculosis. Antimicrob Agents Chemother 2008; 52 (3) 852-857
    CrossrefPubMedGoogle Scholar
  • 51 Rustomjee R, Lienhardt C, Kanyok T , et al; Gatifloxacin for TB (OFLOTUB) study team. A phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis 2008; 12 (2) 128-138
    PubMedGoogle Scholar
  • 52 Lee J, Lee CH, Kim DK , et al. Retrospective comparison of levofloxacin and moxifloxacin on multidrug-resistant tuberculosis treatment outcomes. Korean J Intern Med 2011; 26 (2) 153-159
    CrossrefPubMedGoogle Scholar
  • 53 Kam KM, Yip CW, Cheung TL, Tang HS, Leung OC, Chan MY. Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of multidrug-resistant Mycobacterium tuberculosis: correlation with ofloxacin susceptibility. Microb Drug Resist 2006; 12 (1) 7-11
    CrossrefPubMedGoogle Scholar
  • 54 Cheng AF, Yew WW, Chan EW, Chin ML, Hui MM, Chan RC. Multiplex PCR amplimer conformation analysis for rapid detection of gyrA mutations in fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates. Antimicrob Agents Chemother 2004; 48 (2) 596-601
    CrossrefPubMedGoogle Scholar
  • 55 Epstein IG, Nair KG, Boyd LJ, Auspitz P. Cycloserine-isoniazid combination therapy in virgin cases of pulmonary tuberculosis. Dis Chest 1958; 33 (4) 371-381
    CrossrefPubMedGoogle Scholar
  • 56 Angel JH, Bhati AL, Devadatta S , et al. A controlled comparison of cycloserine plus ethionamide with cycloserine plus thiacetazone in patients with active pulmonary tuberculosis despite prolonged previous chemotherapy. Tubercle 1963; 44: 215-224
    CrossrefPubMedGoogle Scholar
  • 57 Mathys V, Wintjens R, Lefevre P , et al. Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2009; 53 (5) 2100-2109
    CrossrefPubMedGoogle Scholar
  • 58 The Therapeutics Trials Committee of the Swedish National Association Against Tuberculosis. Para-aminosalicylic acid treatment in pulmonary tuberculosis. Am Rev Tuberc 1950; 61 (5) 597-612
    PubMedGoogle Scholar
  • 59 Barry VC, Belton JG, Conalty ML , et al. A new series of phenazines (rimino-compounds) with high antituberculosis activity. Nature 1957; 179 (4568) 1013-1015
    CrossrefPubMedGoogle Scholar
  • 60 Dooley KE, Obuku EA, Durakovic N, Belitsky V, Mitnick C, Nuermberger EL. on behalf of the Efficacy Subgroup, RESIST-TB. World Health Organization Group 5 drugs for the treatment of drug-resistant tuberculosis: unclear efficacy or untapped potential?. J Infect Dis 2012;
    PubMedGoogle Scholar
  • 61 Xu J, Lu Y, Fu L , et al. In vitro and in vivo activity of clofazimine against Mycobacterium tuberculosis persisters. Int J Tuberc Lung Dis 2012; 16 (8) 1119-1125
    CrossrefPubMedGoogle Scholar
  • 62 Dey T, Brigden G, Cox H, Shubber Z, Cooke G, Ford N. Outcomes of clofazimine for the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis. J Antimicrob Chemother 2012;
    PubMedGoogle Scholar
  • 63 Xu HB, Jiang RH, Tang SJ, Li L, Xiao HP. Role of clofazimine in the treatment of multidrug-resistant tuberculosis: a retrospective observational cohort assessment. J Antimicrob Chemother 2012;
    PubMedGoogle Scholar
  • 64 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 (5) 560-567
    PubMedGoogle Scholar
  • 65 Sotgiu G, Centis R, D'Ambrosio L , et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J 2012;
    PubMedGoogle Scholar
  • 66 Cox H, Ford N. Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis 2012; 16 (4) 447-454
    CrossrefPubMedGoogle Scholar
  • 67 Koh WJ, Kwon OJ, Gwak H , et al. Daily 300.  mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis. J Antimicrob Chemother 2009; 64 (2) 388-391
    CrossrefPubMedGoogle Scholar
  • 68 Xu HB, Jiang RH, Li L, Xiao HP. Linezolid in the treatment of MDR-TB: a retrospective clinical study. Int J Tuberc Lung Dis 2012; 16 (3) 358-363
    CrossrefPubMedGoogle Scholar
  • 69 Migliori GB, Eker B, Richardson MD , et al; TBNET Study Group. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur Respir J 2009; 34 (2) 387-393
    CrossrefPubMedGoogle Scholar
  • 70 Singla R, Caminero JA, Jaiswal A , et al. Linezolid: an effective, safe and cheap drug for patients failing multidrug-resistant tuberculosis treatment in India. Eur Respir J 2012; 39 (4) 956-962
    CrossrefPubMedGoogle Scholar
  • 71 Chambers HF, Turner J, Schecter GF, Kawamura M, Hopewell PC. Imipenem for treatment of tuberculosis in mice and humans. Antimicrob Agents Chemother 2005; 49 (7) 2816-2821
    CrossrefPubMedGoogle Scholar
  • 72 De Lorenzo S, Alffenaar JW, Sotgiu G , et al. Efficacy and safety of meropenem/clavunate added to linezolid containing regimens in the treatment of M/XDR-TB. Eur Respir J 2012;
    PubMedGoogle Scholar
  • 73 Andini N, Nash KA. Intrinsic macrolide resistance of the Mycobacterium tuberculosis complex is inducible. Antimicrob Agents Chemother 2006; 50 (7) 2560-2562
    CrossrefPubMedGoogle Scholar
  • 74 Cavalieri SJ, Biehle JR, Sanders Jr WE. Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 1995; 39 (7) 1542-1545
    CrossrefPubMedGoogle Scholar
  • 75 Mitnick CD, Shin SS, Seung KJ , et al. Comprehensive treatment of extensively drug-resistant tuberculosis. N Engl J Med 2008; 359 (6) 563-574
    CrossrefPubMedGoogle Scholar
  • 76 Tahaoğlu K, Törün T, Sevim T , et al. The treatment of multidrug-resistant tuberculosis in Turkey. N Engl J Med 2001; 345 (3) 170-174
    CrossrefPubMedGoogle Scholar
  • 77 Xu HB, Jiang RH, Li L. Pulmonary resection for patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. J Antimicrob Chemother 2011; 66 (8) 1687-1695
    CrossrefPubMedGoogle Scholar
  • 78 Kempker RR, Vashakidze S, Solomonia N, Dzidzikashvili N, Blumberg HM. Surgical treatment of drug-resistant tuberculosis. Lancet Infect Dis 2012; 12 (2) 157-166
    CrossrefPubMedGoogle Scholar
  • 79 Pomerantz BJ, Cleveland Jr JC, Olson HK, Pomerantz M. Pulmonary resection for multi-drug resistant tuberculosis. J Thorac Cardiovasc Surg 2001; 121 (3) 448-453
    CrossrefPubMedGoogle Scholar
  • 80 Blumberg HM, Burman WJ, Chaisson RE , et al; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med 2003; 167 (4) 603-662
    CrossrefPubMedGoogle Scholar
  • 81 Seddon JA, Hesseling AC, Marais BJ , et al. Paediatric use of second-line anti-tuberculosis agents: a review. Tuberculosis (Edinb) 2012; 92 (1) 9-17
    CrossrefPubMedGoogle Scholar
  • 82 Schaaf HS, Marais BJ. Management of multidrug-resistant tuberculosis in children: a survival guide for paediatricians. Paediatr Respir Rev 2011; 12 (1) 31-38
    CrossrefPubMedGoogle Scholar
  • 83 Ettehad D, Schaaf HS, Seddon JA, Cooke GS, Ford N. Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12 (6) 449-456
    CrossrefPubMedGoogle Scholar
  • 84 Gandhi NR, Moll A, Sturm 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 (9547) 1575-1580
    CrossrefPubMedGoogle Scholar
  • 85 Blanc FX, Sok T, Laureillard D , et al; CAMELIA (ANRS 1295–CIPRA KH001) Study Team. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med 2011; 365 (16) 1471-1481
    CrossrefPubMedGoogle Scholar
  • 86 Havlir DV, Kendall MA, Ive P , et al; AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med 2011; 365 (16) 1482-1491
    CrossrefPubMedGoogle Scholar
  • 87 Abdool Karim SS, Naidoo K, Grobler A , et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med 2011; 365 (16) 1492-1501
    CrossrefPubMedGoogle Scholar
  • 88 Johnston JC, Shahidi NC, Sadatsafavi M, Fitzgerald JM. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS ONE 2009; 4 (9) e6914
    CrossrefPubMedGoogle Scholar
  • 89 Jacobson KR, Tierney DB, Jeon CY, Mitnick CD, Murray MB. Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis. Clin Infect Dis 2010; 51 (1) 6-14
    CrossrefPubMedGoogle Scholar
  • 90 Jeon DS, Kim DH, Kang HS , et al. Survival and predictors of outcomes in non-HIV-infected patients with extensively drug-resistant tuberculosis. Int J Tuberc Lung Dis 2009; 13 (5) 594-600
    PubMedGoogle Scholar
  • 91 Kwon YS, Kim YH, Suh GY , et al. Treatment outcomes for HIV-uninfected patients with multidrug-resistant and extensively drug-resistant tuberculosis. Clin Infect Dis 2008; 47 (4) 496-502
    CrossrefPubMedGoogle Scholar
  • 92 Kurbatova EV, Taylor A, Gammino VM , et al. Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects. Tuberculosis (Edinb) 2012; 92 (5) 397-403
    CrossrefPubMedGoogle Scholar
  • 93 Kurbatova EV, Gammino VM, Bayona J , et al. Frequency and type of microbiological monitoring of multidrug-resistant tuberculosis treatment. Int J Tuberc Lung Dis 2011; 15 (11) 1553-1555 , i
    CrossrefPubMedGoogle Scholar
  • 94 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 (9) 650-659
    CrossrefPubMedGoogle Scholar
  • 95 Gammino VM, Taylor AB, Rich ML , et al. Bacteriologic monitoring of multidrug-resistant tuberculosis patients in five DOTS-Plus pilot projects. Int J Tuberc Lung Dis 2011; 15 (10) 1315-1322
    CrossrefPubMedGoogle Scholar
  • 96 Nathanson E, Gupta R, Huamani P , et al. Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative. Int J Tuberc Lung Dis 2004; 8 (11) 1382-1384
    PubMedGoogle Scholar
  • 97 Bloss E, Kuksa L, Holtz TH , et al. Adverse events related to multidrug-resistant tuberculosis treatment, Latvia, 2000–2004. Int J Tuberc Lung Dis 2010; 14 (3) 275-281
    PubMedGoogle Scholar
  • 98 WHO. Management of MDR-TB: A Field Guide. Geneva, Switzerland: World Health Organization; 2008
    Google Scholar
  • 99 Palliative Care, WHO. Symptom Management and End-of-Life Care. Geneva, Switzerland: World Health Organization. 2004
    Google Scholar
  • 100 Temel JS, Greer JA, Muzikansky A , et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010; 363 (8) 733-742
    CrossrefPubMedGoogle Scholar
  • 101 Fitzpatrick C, Floyd K. A systematic review of the cost and cost effectiveness of treatment for multidrug-resistant tuberculosis. Pharmacoeconomics 2012; 30 (1) 63-80
    CrossrefPubMedGoogle Scholar
  • 102 Grosset JH, Singer TG, Bishai WR. New drugs for the treatment of tuberculosis: hope and reality. Int J Tuberc Lung Dis 2012; 16 (8) 1005-1014
    CrossrefPubMedGoogle Scholar
  • 103 Diacon AH, Pym A, Grobusch M , et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med 2009; 360 (23) 2397-2405
    CrossrefPubMedGoogle Scholar
  • 104 Diacon AH, Donald PR, Pym A , et al. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob Agents Chemother 2012; 56 (6) 3271-3276
    CrossrefPubMedGoogle Scholar
  • 105 Gler MT, Skripconoka V, Sanchez-Garavito E , et al. Delamanid for multidrug-resistant pulmonary tuberculosis. N Engl J Med 2012; 366 (23) 2151-2160
    CrossrefPubMedGoogle Scholar
  • 106 Diacon AH, Dawson R, von Groote-Bidlingmaier F , et al. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet 2012; 380 (9846) 986-993
    CrossrefPubMedGoogle Scholar