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      Treatment outcomes of patients with multidrug-resistant and extensively drug resistant tuberculosis in Hunan Province, China

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          Abstract

          Background

          The worldwide emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has posed additional challenges for global tuberculosis (TB) control efforts, as limited treatment options are available and treatment outcomes are often sub-optimal. This study determined treatment outcomes among a cohort of MDR-TB and XDR-TB patients in Hunan Province, China, and identified factors associated with poor treatment outcomes.

          Methods

          We conducted a retrospective study using data obtained from medical records of TB patients in Hunan Chest Hospital, and from the internet-based TB management information system managed by the Tuberculosis Control Institute of Hunan Province, for the period 2011 to 2014. Treatment outcomes were assessed for patients diagnosed with MDR-TB (TB resistant to at least isoniazid and rifampicin) and XDR-TB (MDR-TB plus resistance to any fluoroquinolone and at least 1 second-line injectable drug). Cumulative incidence functions were used to estimate time to events (i.e. poor treatment outcomes, loss to follow-up, and unfavourable treatment outcomes); and a competing-risks survival regression model was used to identify predictors of treatment outcomes.

          Result

          Of 481 bacteriologically-confirmed patients, with a mean age of 40 years (standard deviation SD ± 13 years), 10 (2%) had XDR-TB and the remainder (471; 98%) had MDR-TB. For the entire cohort, treatment success was 57% ( n = 275); 58% ( n = 272) for MDR-TB and 30% ( n = 3) for XDR-TB. Overall, 27% were lost to follow-up ( n = 130), 27% ( n = 126) for MDR-TB and 40% ( n = 4) for XDR-TB; and 16% had a poor treatment outcome ( n = 76), 15% for MDR-TB and 30% ( n = 3) for XDR-TB. Of the 10 XDR-TB patients, 3 (30%) completed treatment, 3 (30%) died and 4 (40%) were lost to follow-up. Of the 471 MDR-TB patients, 258 (57%) were cured, 16 (3%) completed treatment, 13 (3%) died, 60 (13%) experienced treatment failure, and 126 (27%) were lost to follow-up. Resistance to ofloxacin was an independent predictor of poor (AHR = 3.1; 95%CI = 1.5, 6.3), and unfavourable (AHR = 1.7; 95%CI = 1.07, 2.9) treatment outcomes. Patients who started treatment during 2011–2012 (AHR = 2.8; 95% CI = 1.5, 5.3) and 2013 (AHR = 2.1; 95% CI = 1.2, 3.9) had poorer treatment outcomes compared to patients who started treatment during 2014.

          Conclusion

          Patients with MDR-TB and XDR-TB had low rates of treatment success in Hunan Province, especially among patients who started treatment during 2011 to 2013, with evidence of improved treatment outcomes in 2014. Resistance to ofloxacin was an independent predictor of poor treatment outcomes.

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          Most cited references28

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          Multidrug-resistant and extensively drug-resistant tuberculosis: a threat to global control of tuberculosis.

          Although progress has been made to reduce global incidence of drug-susceptible tuberculosis, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis during the past decade threatens to undermine these advances. However, countries are responding far too slowly. Of the estimated 440,000 cases of MDR tuberculosis that occurred in 2008, only 7% were identified and reported to WHO. Of these cases, only a fifth were treated according to WHO standards. Although treatment of MDR and XDR tuberculosis is possible with currently available diagnostic techniques and drugs, the treatment course is substantially more costly and laborious than for drug-susceptible tuberculosis, with higher rates of treatment failure and mortality. Nonetheless, a few countries provide examples of how existing technologies can be used to reverse the epidemic of MDR tuberculosis within a decade. Major improvements in laboratory capacity, infection control, performance of tuberculosis control programmes, and treatment regimens for both drug-susceptible and drug-resistant disease will be needed, together with a massive scale-up in diagnosis and treatment of MDR and XDR tuberculosis to prevent drug-resistant strains from becoming the dominant form of tuberculosis. New diagnostic tests and drugs are likely to become available during the next few years and should accelerate control of MDR and XDR tuberculosis. Equally important, especially in the highest-burden countries of India, China, and Russia, will be a commitment to tuberculosis control including improvements in national policies and health systems that remove financial barriers to treatment, encourage rational drug use, and create the infrastructure necessary to manage MDR tuberculosis on a national scale. Copyright 2010 Elsevier Ltd. All rights reserved.
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            National survey of drug-resistant tuberculosis in China.

            The available information on the epidemic of drug-resistant tuberculosis in China is based on local or regional surveys. In 2007, we carried out a national survey of drug-resistant tuberculosis in China. We estimated the proportion of tuberculosis cases in China that were resistant to drugs by means of cluster-randomized sampling of tuberculosis cases in the public health system and testing for resistance to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and streptomycin and the second-line drugs ofloxacin and kanamycin. We used the results from this survey and published estimates of the incidence of tuberculosis to estimate the incidence of drug-resistant tuberculosis. Information from patient interviews was used to identify factors linked to drug resistance. Among 3037 patients with new cases of tuberculosis and 892 with previously treated cases, 5.7% (95% confidence interval [CI], 4.5 to 7.0) and 25.6% (95% CI, 21.5 to 29.8), respectively, had multidrug-resistant (MDR) tuberculosis (defined as disease that was resistant to at least isoniazid and rifampin). Among all patients with tuberculosis, approximately 1 of 4 had disease that was resistant to isoniazid, rifampin, or both, and 1 of 10 had MDR tuberculosis. Approximately 8% of the patients with MDR tuberculosis had extensively drug-resistant (XDR) tuberculosis (defined as disease that was resistant to at least isoniazid, rifampin, ofloxacin, and kanamycin). In 2007, there were 110,000 incident cases (95% CI, 97,000 to 130,000) of MDR tuberculosis and 8200 incident cases (95% CI, 7200 to 9700) of XDR tuberculosis. Most cases of MDR and XDR tuberculosis resulted from primary transmission. Patients with multiple previous treatments who had received their last treatment in a tuberculosis hospital had the highest risk of MDR tuberculosis (adjusted odds ratio, 13.3; 95% CI, 3.9 to 46.0). Among 226 previously treated patients with MDR tuberculosis, 43.8% had not completed their last treatment; most had been treated in the hospital system. Among those who had completed treatment, tuberculosis developed again in most of the patients after their treatment in the public health system. China has a serious epidemic of drug-resistant tuberculosis. MDR tuberculosis is linked to inadequate treatment in both the public health system and the hospital system, especially tuberculosis hospitals; however, primary transmission accounts for most cases. (Funded by the Chinese Ministry of Health.).
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              Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects.

              The Objective of this analysis was to identify predictors of death, failure, and default among MDR-TB patients treated with second-line drugs in DOTS-plus projects in Estonia, Latvia, Philippines, Russia, and Peru, 2000-2004. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using multivariable regression. Of 1768 patients, treatment outcomes were: cure/completed - 1156 (65%), died - 200 (11%), default - 241 (14%), failure - 118 (7%). Independent predictors of death included: age>45 years (RR = 1.90 (95%CI 1.29-2.80), HIV infection (RR = 4.22 (2.65-6.72)), extrapulmonary disease (RR = 1.54 (1.04-2.26)), BMI<18.5 (RR = 2.71 (1.91-3.85)), previous use of fluoroquinolones (RR = 1.91 (1.31-2.78)), resistance to any thioamide (RR = 1.59 (1.14-2.22)), baseline positive smear (RR = 2.22 (1.60-3.10)), no culture conversion by 3rd month of treatment (RR = 1.69 (1.19-2.41)); failure: cavitary disease (RR = 1.73 (1.07-2.80)), resistance to any fluoroquinolone (RR = 2.73 (1.71-4.37)) and any thioamide (RR = 1.62 (1.12-2.34)), and no culture conversion by 3rd month (RR = 5.84 (3.02-11.27)); default: unemployment (RR = 1.50 (1.12-2.01)), homelessness (RR = 1.52 (1.00-2.31)), imprisonment (RR = 1.86 (1.42-2.45)), alcohol abuse (RR = 1.60 (1.18-2.16)), and baseline positive smear (RR = 1.35 (1.07-1.71)). Patients with biomedical risk factors for treatment failure or death should receive heightened medical attention. To prevent treatment default, management of patients who are unemployed, homeless, alcoholic, or have a prison history requires extra measures to insure treatment completion. Published by Elsevier Ltd.
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                Author and article information

                Contributors
                kefyalew.alene@anu.edu.au
                46498321@qq.com
                kerri.viney@anu.edu.au
                emma.mcbryde@jcu.edu.au
                angky2005@126.com
                liqiong99@126.com
                darren.gray@anu.edu.au
                Director.RSPH@anu.edu.au
                xuzuhui@126.com
                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central (London )
                1471-2334
                16 August 2017
                16 August 2017
                2017
                : 17
                : 573
                Affiliations
                [1 ]ISNI 0000 0001 2180 7477, GRID grid.1001.0, Research School of Population Health, College of Medicine, Biology and Environment, , The Australian National University, ; Canberra, ACT Australia
                [2 ]ISNI 0000 0000 8539 4635, GRID grid.59547.3a, Institute of Public Health, College of Medicine and Health Sciences, , University of Gondar, ; Gondar, Ethiopia
                [3 ]Department of MDR-TB, Internal Medicine, Hunan Chest hospital, Changsha city, Hunan Province China
                [4 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Centre for Global Health, , Department of Public Health Sciences, Karolinska Institutet, ; Stockholm, Sweden
                [5 ]ISNI 0000 0004 0474 1797, GRID grid.1011.1, Australian Institute of Tropical Health and Medicine, , James Cook University, ; Townsville, QLD Australia
                [6 ]Department of Director’s Office, Tuberculosis Control Institute of Hunan Province, Changsha city, Hunan Province China
                [7 ]Department of Tuberculosis Control, Tuberculosis Control Institute of Hunan Province, Changsha city, Hunan Province China
                Article
                2662
                10.1186/s12879-017-2662-8
                5559784
                28814276
                97070462-1048-4923-8bfa-4abab8b881d2
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 9 May 2017
                : 1 August 2017
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Infectious disease & Microbiology
                multidrug-resistant,extensively drug resistant,tuberculosis,treatment outcomes,china

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