Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Kvasnovsky C[original query] |
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Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis
Ahmad N , Ahuja SD , Akkerman OW , Alffenaar JC , Anderson LF , Baghaei P , Bang D , Barry PM , Bastos ML , Behera D , Benedetti A , Bisson GP , Boeree MJ , Bonnet M , Brode SK , Brust JCM , Cai Y , Caumes E , Cegielski JP , Centis R , Chan PC , Chan ED , Chang KC , Charles M , Cirule A , Dalcolmo MP , D'Ambrosio L , de Vries G , Dheda K , Esmail A , Flood J , Fox GJ , Frechet-Jachym M , Fregona G , Gayoso R , Gegia M , Gler MT , Gu S , Guglielmetti L , Holtz TH , Hughes J , Isaakidis P , Jarlsberg L , Kempker RR , Keshavjee S , Khan FA , Kipiani M , Koenig SP , Koh WJ , Kritski A , Kuksa L , Kvasnovsky CL , Kwak N , Lan Z , Lange C , Laniado-Laborin R , Lee M , Leimane V , Leung CC , Leung EC , Li PZ , Lowenthal P , Maciel EL , Marks SM , Mase S , Mbuagbaw L , Migliori GB , Milanov V , Miller AC , Mitnick CD , Modongo C , Mohr E , Monedero I , Nahid P , Ndjeka N , O'Donnell MR , Padayatchi N , Palmero D , Pape JW , Podewils LJ , Reynolds I , Riekstina V , Robert J , Rodriguez M , Seaworth B , Seung KJ , Schnippel K , Shim TS , Singla R , Smith SE , Sotgiu G , Sukhbaatar G , Tabarsi P , Tiberi S , Trajman A , Trieu L , Udwadia ZF , van der Werf TS , Veziris N , Viiklepp P , Vilbrun SC , Walsh K , Westenhouse J , Yew WW , Yim JJ , Zetola NM , Zignol M , Menzies D . Lancet 2018 392 (10150) 821-834 BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14, 0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I(2) method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America. |
Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study
Sharma A , Hill A , Kurbatova E , van der Walt M , Kvasnovsky C , Tupasi TE , Caoili JC , Gler MT , Volchenkov GV , Kazennyy BY , Demikhova OV , Bayona J , Contreras C , Yagui M , Leimane V , Cho SN , Kim HJ , Kliiman K , Akksilp S , Jou R , Ershova J , Dalton T , Cegielski P . Lancet Infect Dis 2017 17 (7) 707-715 BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12.4% (95% prediction interval 9.4-16.2) in India, 8.9% (4.5-11.7) in the Philippines, 32.5% (27.0-35.8) in Russia, and 5.7% (3.0-7.6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8.9% (95% prediction interval 5.1-12.9) in India, 9.0% (4.0-14.7) in the Philippines, 9.0% (4.8-14.2) in Russia, and 8.5% (2.5-14.7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. |
Treatment outcomes for patients with extensively drug-resistant tuberculosis, KwaZulu-Natal and Eastern Cape Provinces, South Africa
Kvasnovsky CL , Cegielski JP , van der Walt ML . Emerg Infect Dis 2016 22 (9) 1529-36 We analyzed data for a retrospective cohort of patients treated for extensively drug-resistant tuberculosis in 2 provinces in South Africa and compared predictors of treatment outcome in HIV-positive patients who received or had not received antiretroviral drugs with those for HIV-negative patients. Overall, 220 (62.0%) of 355 patients were HIV positive. After 2 years, 34 (10.3%) of 330 patients with a known HIV status and known outcome had a favorable outcome. Multivariate analysis showed that predictors of favorable outcome were negative results for acid-fast bacilli by sputum microscopy at start of treatment and weight >50 kg. HIV-positive patients were more likely to have an unfavorable outcome. The strongest predictor of unfavorable outcome was weight <50 kg. Overall outcomes were poor. HIV status was not a predictor of favorable outcome, but HIV-positive patients were more likely to have an unfavorable outcome. These results underscore the need for timely and adequate treatment for tuberculosis and HIV infection. |
Association between regimen composition and treatment response in patients with multidrug-resistant tuberculosis: A prospective cohort study
Yuen CM , Kurbatova EV , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Ershova J , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Vasilyeva IA , Dalton T , Cegielski JP . PLoS Med 2015 12 (12) e1001932 BACKGROUND: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen. METHODS AND FINDINGS: We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse. CONCLUSIONS: MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens. |
Multidrug-resistant tuberculosis treatment outcomes in relation to treatment, initial and acquired second-line drug resistance
Cegielski JP , Kurbatova E , van der Walt M , Brand J , Ershova J , Tupasi T , Campos Caoili J , Dalton T , Contreras C , Yagui M , Bayona J , Kvasnovsky C , Leimane V , Kuksa L , Chen MP , Via LE , Hwang SH , Wolfgang M , Volchenkov GV , Somova T , Smith SE , Akksilp S , Wattanaamornkiet W , Kim HJ , Kim CK , Kazennyy BY , Khorosheva T , Kliiman K , Viiklepp P , Jou R , Huang AS , Vasilyeva IA , Demikhova OV . Clin Infect Dis 2015 62 (4) 418-430 BACKGROUND: Resistance to second-line drugs (SLD) develops during treatment of multidrug-resistant (MDR) tuberculosis (TB), but the impact on treatment outcome has not been determined. OBJECTIVES: To determine the relationship with treatment outcomes of (1) initial versus acquired drug resistance and (2) treatment regimens. METHODS: MDR-TB patients starting SLD treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectables (SLI), and (2) treatment regimens. RESULTS: Of 1,244 MDR-TB patients, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR-TB, 69.7% with initial resistance to either a fluoroquinolone or SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial XDR-TB, and 13.0% with acquired XDR-TB (P<0.0001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of proven effective drugs increased from ≤1 to ≥5 (P<0.0001 for trend); while acquired drug resistance decreased from 12%-16% range, depending on the drug, down to 0%-2% (P<0.0001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (CL 0.56,0.69) for each increment in drug resistance and increased 2.1-fold (1.40,3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient and program variables were also associated with treatment outcome. CONCLUSION: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance. |
Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries
Kurbatova EV , Dalton T , Ershova J , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Cegielski JP . Emerg Infect Dis 2015 21 (6) 977-83 Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens. |
Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies
Kurbatova EV , Cegielski JP , Lienhardt C , Akksilp R , Bayona J , Becerra MC , Caoili J , Contreras C , Dalton T , Danilovits M , Demikhova OV , Ershova J , Gammino VM , Gelmanova I , Heilig CM , Jou R , Kazennyy B , Keshavjee S , Kim HJ , Kliiman K , Kvasnovsky C , Leimane V , Mitnick CD , Quelapio I , Riekstina V , Smith SE , Tupasi T , van der Walt M , Vasilyeva IA , Via LE , Viiklepp P , Volchenkov G , Walker AT , Wolfgang M , Yagui M , Zignol M . Lancet Respir Med 2015 3 (3) 201-9 BACKGROUND: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis. METHODS: We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling. FINDINGS: We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0.0001). Furthermore, conversion status at 6 months (adjusted OR 14.07 [95% CI 10.05-19.71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4.12 [95% CI 2.25-7.54]) or who had unknown HIV infection (3.59 [1.96-6.58]), but not in those who were HIV positive (0.38 [0.12-1.18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27.3% [95% confidence limit 16.6-41.4]) and high specificity (89.8% [82.3-94.4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91.8% [85.9-95.4]), but moderate specificity (57.8% [42.5-71.6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment. INTERPRETATION: Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis. FUNDING: US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention. |
Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis
Cegielski JP , Dalton T , Yagui M , Wattanaamornkiet W , Volchenkov GV , Via LE , Van Der Walt M , Tupasi T , Smith SE , Odendaal R , Leimane V , Kvasnovsky C , Kuznetsova T , Kurbatova E , Kummik T , Kuksa L , Kliiman K , Kiryanova EV , Kim H , Kim CK , Kazennyy BY , Jou R , Huang WL , Ershova J , Erokhin VV , Diem L , Contreras C , Cho SN , Chernousova LN , Chen MP , Caoili JC , Bayona J , Akksilp S . Clin Infect Dis 2014 59 (8) 1049-63 INTRODUCTION: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis (TB) is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. SUBJECTS AND METHODS: To assess the GLC's impact, we followed adults with pulmonary MDRTB from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLD) in nine countries that volunteered to participate, five countries that met GLC criteria and four countries that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) TB, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLI). The relative risk (95% confidence interval) of acquired resistance was lower at GLC-approved sites: 0.27 (0.16,0.47) for XDRTB, 0.28 (0.17,0.45) for FQ, and 0.15 (0.06,0.39) to 0.60 (0.34,1.05) for three different SLI. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios were 0.21 (0.07,0.62) for acquired XDRTB and 0.23 (0.09,0.59) for acquired FQ resistance. CONCLUSIONS: Treatment of MDRTB involves substantial risk of acquired resistance to SLD, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. |
Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study
Dalton T , Cegielski P , Akksilp S , Asencios L , Caoili JC , Cho SN , Erokhin VV , Ershova J , Gler MT , Kazennyy BY , Kim HJ , Kliiman K , Kurbatova E , Kvasnovsky C , Leimane V , van der Walt M , Via LE , Volchenkov GV , Yagui MA , Kang H . Lancet 2012 380 (9851) 1406-17 BACKGROUND: The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries. METHODS: From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis. FINDINGS: Among 1278 patients, 43.7% showed resistance to at least one second-line drug, 20.0% to at least one second-line injectable drug, and 12.9% to at least one fluoroquinolone. 6.7% of patients had XDR tuberculosis (range across study sites 0.8-15.2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries. INTERPRETATION: Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies. FUNDING: US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare. |
Extensively drug-resistant TB in Eastern Cape, South Africa: high mortality in HIV negative and HIV positive patients
Kvasnovsky CL , Cegielski JP , Erasmus R , Siwisa NO , Thomas K , Van Der Walt ML . J Acquir Immune Defic Syndr 2011 57 (2) 146-52 BACKGROUND: Tuberculosis is a leading cause of morbidity and mortality worldwide. Patients with extensively drug-resistant tuberculosis (XDR-TB) have had high mortality rates, especially when co-infected with HIV. METHODS: A retrospective cohort study of the first 206 patients treated for XDR-TB in Eastern Cape Province, South Africa, October 2006 - January 2008, a province that has treated multidrug-resistant tuberculosis since 2000. All 206 patients were hospitalized for treatment until monthly sputum specimens were culture-negative. RESULTS: Sixty-five patients diagnosed with XDR-TB died prior to XDR-TB treatment start. Among 195 patients starting treatment with a known HIV status, 108 (55.4%) were HIV positive and 86 patients (44.1%) died during the first year of treatment. HIV positive patients receiving anti-retroviral treatment (ARVs) fared as well as HIV negative patients, and more of both these groups survived than HIV positive patients not on ARVs. However, HIV negative patients experienced more serious adverse events requiring the withdrawal of medications than did HIV positive patients, regardless of the use of ARVs. CONCLUSION: Experience in Eastern Cape Province, South Africa suggests patients can be treated for both XDR-TB and HIV. We have also shown that such combination therapy can be well tolerated by patients. |
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