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      Predictors of Multidrug- and Extensively Drug-Resistant Tuberculosis in a High HIV Prevalence Community

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          Abstract

          Background

          Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control.

          Methods

          We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1∶1∶1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors.

          Results

          We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4–414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1–13.3] and 6.1 [CI 1.8–21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3–52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0–27.6).

          Discussion

          In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.

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          Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

          Flavio Alcantara, Dae-Hyun Kim, Jennifer Furin … (2003)
          Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes. Copyright 2003 Massachusetts Medical Society
          Article 0 comments Cited 107 times – based on 0 reviews     Review now
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            HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality.

            Jason R Andrews, Michelle Scott, Anthony P. Moll … (2010)
            The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) epidemics are rapidly expanding in South Africa. Our initial report of HIV-associated XDR TB in South Africa revealed rapid and near complete mortality. Lower mortality has been described in the literature, but few of these patients have been HIV coinfected. To characterize mortality from MDR and XDR TB in a setting with high HIV-coinfection rates. We conducted a retrospective observational study among 654 MDR and XDR TB cases diagnosed in Tugela Ferry, South Africa, from 2005 to 2007. Demographics and HIV status were abstracted from available medical records. Survival was determined from the date of sputum collection until October 2008 and correlated with year of diagnosis and drug-susceptibility test results. From 2005 to 2007, 272 MDR TB and 382 XDR TB cases were diagnosed; HIV-coinfection rates were 90 and 98%, respectively. One-year mortality was 71% for MDR and 83% for XDR TB patients; 40% of MDR TB and 51% of XDR TB cases died within 30 days of sputum collection. One-year mortality among both MDR and XDR TB patients improved from 2005 to 2007; however, the majority of deaths still occurred within the first 30 days. One-year and 30-day mortality rates were worse with greater degree of drug resistance (P < 0.001). Mortality from MDR and XDR TB in this high HIV-prevalence region is extraordinarily high, particularly within the first 30 days. Efforts to reduce mortality must focus on earlier diagnosis and early initiation of second-line TB and antiretroviral therapy.
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              Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study.

              Keertan Dheda, Karen Shean, Alimuddin Zumla … (2010)
              Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes. In a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion. 195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0.13). Treatment with moxifloxacin (hazard ratio 0.11, 95% CI 0.01-0.82; p=0.03), previous culture-proven multidrug-resistant tuberculosis (5.21, 1.93-14.1; p=0.001), and number of drugs used in a regimen (0.59, 0.45-0.78, p<0.0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0.38, 0.18-0.80; p=0.01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment. In South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity. South African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2010
                Publication date (Electronic): 29 December 2010
                Volume: 5
                Issue: 12
                Electronic Location Identifier: e15735
                Affiliations
                [1 ]Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
                [2 ]Departments of Medicine and Epidemiology & Public Health, Albert Einstein College of Medicine and Montefiore Medical Center, New York, New York, United States of America
                [3 ]Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, New York, New York, United States of America
                [4 ]Philanjalo and Church of Scotland Hospital, Tugela Ferry, KwaZulu-Natal, South Africa
                [5 ]AIDS Program, Yale University School of Medicine, New Haven, Connecticut, United States of America
                [6 ]Departments of Medicine and Epidemiology & Public Health, Albert Einstein College of Medicine and Montefiore Medical Center, New York, New York, United States of America
                University of Delhi, India
                Author notes

                Conceived and designed the experiments: NRG NSS JRA. Performed the experiments: NRG NSS DW JRA. Analyzed the data: NRG NSS DW JRA. Contributed reagents/materials/analysis tools: NRG NSS APM. Wrote the paper: NRG NSS JRA.

                Article
                Publisher ID: PONE-D-10-02276
                DOI: 10.1371/journal.pone.0015735
                PMC ID: 3012092
                PubMed ID: 21209951
                SO-VID: 3a71f250-9019-489a-af7d-6ffe9c4e059d
                Copyright © Andrews et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Date received : 10 September 2010
                Date accepted : 25 November 2010
                Page count
                Pages: 6
                Categories
                Subject: Research Article
                Subject: Medicine
                Subject: Epidemiology
                Subject: Infectious Disease Epidemiology
                Subject: Infectious Diseases
                Subject: Bacterial Diseases
                Subject: Tuberculosis
                Subject: Extensively Drug-Resistant Tuberculosis
                Subject: Multi-Drug-Resistant Tuberculosis
                Subject: Mycobacterium
                Subject: Viral Diseases
                Subject: HIV
                Subject: Infectious Disease Control
                Subject: Pulmonology
                Subject: Respiratory Infections
                Subject: Lower Respiratory Tract Infections

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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