Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis

James C Johnston, Neal C Shahidi, Mohsen Sadatsafavi, J Mark Fitzgerald, James C Johnston, Neal C Shahidi, Mohsen Sadatsafavi, J Mark Fitzgerald

Abstract

Background: Treatment outcomes for multidrug-resistant Mycobacterium Tuberculosis (MDRTB) are generally poor compared to drug sensitive disease. We sought to estimate treatment outcomes and identify risk factors associated with poor outcomes in patients with MDRTB.

Methodology/principal findings: We performed a systematic search (to December 2008) to identify trials describing outcomes of patients treated for MDRTB. We pooled appropriate data to estimate WHO-defined outcomes at the end of treatment and follow-up. Where appropriate, pooled covariates were analyzed to identify factors associated with worse outcomes. Among articles identified, 36 met our inclusion criteria, representing 31 treatment programmes from 21 countries. In a pooled analysis, 62% [95% CI 57-67] of patients had successful outcomes, while 13% [9]-[17] defaulted, 11% [9]-[13] died, and 2% [1]-[4] were transferred out. Factors associated with worse outcome included male gender 0.61 (OR for successful outcome) [0.46-0.82], alcohol abuse 0.49 [0.39-0.63], low BMI 0.41[0.23-0.72], smear positivity at diagnosis 0.53 [0.31-0.91], fluoroquinolone resistance 0.45 [0.22-0.91] and the presence of an XDR resistance pattern 0.57 [0.41-0.80]. Factors associated with successful outcome were surgical intervention 1.91 [1.44-2.53], no previous treatment 1.42 [1.05-1.94], and fluoroquinolone use 2.20 [1.19-4.09].

Conclusions/significance: We have identified several factors associated with poor outcomes where interventions may be targeted. In addition, we have identified high rates of default, which likely contributes to the development and spread of MDRTB.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Forest plots of covariates.
Figure 1. Forest plots of covariates.
Figure 2. Summary of literature search and…
Figure 2. Summary of literature search and study selection.

References

    1. World Health Organization/International Union Against Tuberculosis and Lung Disease. Geneva, Switzerland: WHO; 2007. Global Project on Anti-Tuberculosis Drug Resistance Surveillance. Anti-tuberculosis drug resistance in the world: report no 4. Available: . Accessed: 2009 Aug 12.
    1. World Health Organization. Geneva: WHO; 2007. The Global MDR-TB & XDR-TB Response Plan 2006–2007. Available: . Accessed: 2009 Aug 12.
    1. Ghandi NR, Moll A, Sturm AW, Pawinski R, Govender T, 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;368:1575–1580.
    1. Mukherjee JS, Rich ML, Socci AR, Joseph JK, Viru FA, et al. Programmes and principles for management of multidrug-resistant tuberculosis. Lancet. 2004;372:474–481.
    1. Sharma SK, Mohan A. Multidrug-Resistant Tuberculosis: A menace that threatens to destabilize tuberculosis control. Chest. 2006;130:162–272.
    1. Chan E, Iseman M. Multidrug-resistant and extensively drug-resistant tuberculosis: a review. Curr Opinion in Inf Dis. 2008;21(6):587–595.
    1. Mitnick CD, Castro KG, Harrington M, Sacks LV, Burman W. Randomized Trials to Optimize Treatment of Multidrug-Resistant Tuberculosis. PLOS Med. 2007;11:1730–1734.
    1. Caminero JA. Treatment of multidrug-resistant tuberculosis: evidence and controversies. Int J Tuberc Lung Dis. 2006;8:829–837.
    1. Laserson K, Thorpe L, Lemaine V, Weyer K, Mitnick CD, et al. Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis2005; 2005;9:640–45.
    1. World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis emergency update 2008. 2008. Geneva, Switzerland: Available: . Accessed 2009 Aug 12.
    1. Avendano M, Goldstein RS. Multidrug-resistant tuberculosis: Long term follow-up of 40 non-HIV-infected patients. Can Respir J. 2000;7(5):383–389.
    1. Banerjee R, Allen J, Westenhouse J, Oh P, Elms W, et al. Extensively Drug-Resistant Tuberculosis in California, 1993–2006. Clinical Infectious Diseases 2008; 2008;47:450–7.
    1. Bartu V, Hricikova I, Kopecka E, Vasakova M. Results of treatment of multiresistant tuberculosis. CasopisLekaruCeskych. 2003;142(4):226–8.
    1. Burgos M, Gonzalez LC, Paz EA, Gournis E, Kawamura LM, et al. Treatment of multidrug-resistant tuberculosis in San Francisco: An outpatient-based approach. Clinical Infectious Diseases. 2005;40:968–75.
    1. Chiang C-Y, Enarson DA, Yu M-C, Bai KJ, Huang RM, et al. Outcome of pulmonary multidrug-resistant tuberculosis: a 6-yr follow-up study. Eur Respir J. 2006;28:980–985.
    1. Cox HS, Kalon S, Allamuratova S, Sizaire V, Rusch-Gerdes S, et al. Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures. PLoS ONE. 2007;2:e1126.
    1. Escudero E, Pena JM, Alvarez-Sala R, Vazquez JJ, Ortega A, et al. Multidrug-resistant tuberculosis without HIV infection: success with individualised therapy. Int J Tuberc Lung Dis. 2006;10(4):409–14.
    1. Ferrara G, Richeldi L, Bugiani M, Cirillo D, Besozzi G, et al. Management of multidrug-resistant tuberculosis in Italy. Int J Tuberc Lung Dis. 2005;9(5):507–13.
    1. Goble M, Iseman MD, Madsen LA, Waite D, Ackerson L, et al. Treatment of 171 Patients with Pulmonary Tuberculosis Resistant to Isoniazid and Rifampin. NEJM. 1993;328(8):527–32.
    1. Granich RM, Oh P, Lewis B, Porco TC, Flood J, et al. Multidrug resistance among persons with tuberculosis in California, 1994–2003. JAMA. 2005;293(22):2732–2739,2726.
    1. Hersi A, Elwood K, Cowie R, Kunimoto D, Long R. Multidrug-resistant tuberculosis in Alberta and British Columbia, 1989 to 1998. Can Respir J. 1999;6(2):155–160.
    1. Holtz TH, Sternberg M, Kammerer S, Laserson KF, Riekstina V, et al. Time to sputum culture conversion in multidrug-resistant tuberculosis: Predictors and relationship to treatment outcome. Ann Intern Med. 2006;144(9):650–9.
    1. Keshavjee S, Gelmanova IY, Farmer PE, Mishustin SP, Strelis AK, et al. Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study. Lancet. 2008;372:1403–9.
    1. Kim H-R, Hwang SS, Kim HJ, Lee SM, Yoo CG, et al. Impact of Extensive Drug Resistance on Treatment Outcomes in Non-HIV-Infected Patients with Multidrug-Resistant Tuberculosis. Clin Infect Dis. 2007;45:1290–5.
    1. Kim DH, Kim HJ, Park S-K, Kong SJ, Kim YS, et al. Treatment Outcomes and Long-term Survival in Patients with Extensively Drug-resistant Tuberculosis. Am J Respir Crit Care Med. 2008;178:1075–1082.
    1. Kwon YS, Kim YH, Suh GY, Chung MP, Kim H, et al. Treatment outcomes for HIV-uninfected patients with multidrug-resistant and extensively drug-resistant tuberculosis. Clin Infect Dis. 2008;47(4):496–502.
    1. Leimane V, Riekstina V, Holtz TH, Zarovska E, Skripconoka V, et al. Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study. Lancet. 2005;365:318–26.
    1. Masjedi MR, Tabarsi P, Chitsaz E, Baghaei P, Mirsaeidi M, et al. Outcome of treatment of MDR-TB patients with standardised regimens, Iran, 2002–2006. Int J Tuberc Lung Dis. 2008;12(7):750–5.
    1. Mitnick C, Bayona J, Palacios E, Shin S, Furin J, et al. Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru. NEJM. 2003;348(2):119–28.
    1. Mitnick CD, Shin SS, Seung KJ, Rich ML, Atwood SS, et al. Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis. NEJM. 2008;359(6):563–574.
    1. Narita M, Alonso P, Lauzardo M, Hollender ES, Pitchenik AE, et al. Treatment experience of multidrug-resistant tuberculosis in Florida, 1994–1997. Chest. 2001;120(2):343–8.
    1. O'Riordan P, Schwab U, Logan S, Cooke G, Wilkinson RJ, et al. Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: Case control study. PLoS Medicine. 2008;3(9):e3173.
    1. Palmero DJ, Ambroggi M, Brea A, De Lucas M, Fulgenzi A, et al. Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina. Int J Tuberc Lung Dis. 2004;8(6):778–84.
    1. Park SK, Lee WC, Lee DH, Mitnick CD, Han L, et al. Self-administered, standardized regimens for multidrug-resistant tuberculosis in South Korea. Int J Tuberc Lung Dis. 2004;8(3):361–8.
    1. Shean KP, Willcox PA, Siwendu SN, Laserson KF, Gross L, et al. Treatment outcome and follow-up of multidrug-resistant tuberculosis patients. West Coast/Winelands, South Africa, 1992–2002. Int J Tuberc Lung Dis. 2008;12(10):1182–9.
    1. Shin SS, Pasechnikov AD, Gelmanova IY, Peremitin GG, Strelis AK, et al. Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia. Int J Tuberc Lung Dis. 2006;10(4):402–8.
    1. Suarez PG, Floyd K, Portocarrero J, Alarcon E, Rapiti E, et al. Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru. Lancet. 2002;359:1980–1989.
    1. Tahaoglu K, Torun T, Sevim T, Atac G, Kir A, et al. The Treatment of Multidrug-Resistant Tuberculosis in Turkey. NEJM. 2001;345(3):170–174.
    1. Telzak EE, Sepkowitz K, Alpert P, Mannheimer S, Medard F, et al. Multidrug resistant tuberculosis in patients without HIV infection. NEJM. 1995;333(14):907–11.
    1. Torun T, Tahaoglu K, Ozmen I, Wevim T, Atac G, et al. The role of surgery and fluroquinolones in the treatment of multi-drug resistant tuberculosis. Int J Tuberc Lung Dis. 2007;11(9):979–985.
    1. Tupasi TE, Gupta R, Qualapio MD, Orillaza RB, Mira NR, et al. Feasibility and Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis: A Cohort Study in the Philippines. PLos Medicine. 2006;3(9):1587–1596.
    1. Uffredi M-L, Truffot-Pernot C, Dautzenberg B, Renard M, Jarlier V, et al. An intervention programme for the management of multidrug-resistant tuberculosis in France. Intl J of Antimicrobial Agents. 2007;29:434–439.
    1. Van Deun A, HamidSalim MA, Kumar 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.
    1. Ward HA, Marciniuk DD, Hoeppner VH, Jones W. Treatment outcome of multidrug-resistant tuberculosis among Vietnamese immigrants. Int J Tuberc Lung Dis. 2005;9(2):164–9.
    1. Yew WW, Chan CK, Chau CH, Tam Cm, Leung CC, et al. Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with ofloxacin. Chest. 2000;117(3):744–51.
    1. Yew WW, Chan CK, Leung CC, Chau CH, Tam CM, et al. Comparative roles of levofloxacin and ofloxacin in the treatment of multidrug-resistant tuberculosis: preliminary results of a retrospective study from Honk Kong. Chest. 2003;124:1476–81.
    1. Raviglione MC, Smith IM. XDR Tuberculosis — Implications for Global Public Health. NEJM 2007. 2007;356:656–659.
    1. Chan ED, Laurel V, Strand MJ, Chan JF, Huynh ML, et al. Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis. Am J Crit Care Med. 2004;2004169(10):1103–9.
    1. 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. Tubercle and Lung Disease. 1992;73:59–67.
    1. Chan ED, Strand MJ, Iseman MD. Treatment outcomes in extensively resistant tuberculosis. NEJM. 2008;(6):657–9.
    1. Jeon CY, Hwang SH, Min JH, Prevots DR, Goldfeder LC, et al. Extensively drug-resistant tuberculosis in South Korea: risk factors and treatment outcomes among patients at a tertiary referral hospital. Clin Infect Dis. 2008;46(1):42–9.
    1. Migilori GB, Besozzi G, Girardi E, Kiiman K, Lange C, et al. Clinical and operational value of the extensively drug-resistant tuberculosis definition. Eur Resp J. 2007;30(4):623–6.
    1. Migliori GB, Lange C, Centis R, Sotgui G, Mutterlein R, et al. Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases. Eur Resp J. 2008;31(6):1155–9.
    1. Abba K, Sudarsanam TD, Grobler L, Volmink J. Nutritional supplements for people being treated for active tuberculosis. Cochrane Database Syst Rev. 2008;4:CD006086.
    1. Nathanson E, Lambregts-van Weezenbeek C, Rich ML, Gupta R, Bayhona J, et al. Multidrug-resistant Tuberculosis Management in Resource-limited Settings. Emerg Infect Dis. 2006;12(9):1389–97.
    1. Mathew TA, Yanov SA, Mazitov R, Mishustin SP, Strelis AK, et al. Integration of alcohol use disorders identification and management in the tuberculosis programme in Tomsk Oblast, Russia. 2008. Available: . Accessed 2009 Aug 12.
    1. Jeon CY, Murray MB. Diabetes Mellitus Increases the Risk of Active Tuberculosis: A systematic Review of 13 Observational Studies. PLOS Med. 2008;5(7):e152. doi:10.1371/journal.pmed.0050152.
    1. Kim SH, Hong YP, Lew WJ, Yang SC, Lee EG. Incidence of pulmonary tuberculosis among diabetics. Tubercle Lung Dis. 1995;76:529–523.
    1. Bashar M, Alcabes P, Rom WM, Condos R. Increased Incidence of Multidrug-Resistant Tuberculosis in Diabetic Patients on the Bellevue Chest Service, 1987 to 1997. Chest. 2001;120:1524–1519.
    1. Pablos-Mendez A, Blustein J, Knirsch C. The role of diabetes mellitus in the higher prevalence of tuberculosis among Hispanics. Am J Public Health. 1997;87:574–579.
    1. Raviglione M. Facing Extensively Drug-Resistant Tuberculosis — A Hope and a Challenge. NEJM. 2008;359:636–638.
    1. Frieden TR, Sherman LF, Maw KL, Fujiwara PI, Crawford JT, et al. A Multi-institutional Outbreak of Highly Drug-Resistant Tuberculosis. JAMA. 1996;276(15):1229–35.
    1. Valway SE, Greifinger RB, Papania M, Killburn JO, Woodley C, et al. Multidrug-Resistant Tuberculosis in the New York State Prison System 1990–1991. J Infect Dis. 1994;170:151–6.
    1. Center for Disease Control. Epidemiologic Notes and Reports Nosocomial Transmission of Multidrug-Resistant Tuberculosis Among HIV-Infected Persons–Florida and New York, 1988–1991. MMWR. 1991;40(34):585–91.
    1. Center for Disease Control. Outbreak of Multidrug-Resistant Tuberculosis at a Hospital–New York City, 1991. MMWR. 1991;42(22):427–433,434.
    1. Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet. 2009;9:153–161.

Source: PubMed

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