scholarly journals National treatment outcome and predictors of death and treatment failure in multidrug-resistant tuberculosis in Ethiopia: a 10-year retrospective cohort study

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e040862
Author(s):  
Habteyes Tola ◽  
K Holakouie-Naieni ◽  
Mohammad Ali Mansournia ◽  
Mehdi Yaseri ◽  
Dinka Fikadu Gamtesa ◽  
...  

ObjectivesTreatment success rate in patients treated for multidrug-resistant tuberculosis (MDR-TB) is low, but predictors of treatment failure and death have been under-reported. Thus, we aimed to determine the national proportion of treatment success rate in the past 10 years and factors that predict treatment failure and death in patients with MDR-TB in Ethiopia.SettingA retrospective cohort study with a 10-years follow-up period was conducted in 42 MDR-TB treatment-initiating centres in Ethiopia.ParticipantsA total of 3395 adult patients with MDR-TB who had final treatment outcome and who were treated under national TB programme were included. Data were collected from clinical charts, registration books and laboratory reports. Competing risk survival analysis model with robust standard errors (SE) was used to determine the predictors of treatment failure and death.Primary and secondary outcomesTreatment outcome was a primary outcome whereas predictors of treatment failure and death were a secondary outcome.ResultsThe proportion of treatment success was 75.7%, death rate was 12.8%, treatment failure was 1.7% and lost to follow-up was 9.7%. The significant predictors of death were older age (adjusted hazard ratio (AHR)=1.03; 95% CI 1.03 to 1.05; p<0.001), HIV infection (AHR=2.0; 95% CI 1.6 to 2.4; p<0.001) and presence of any grade of anaemia (AHR=1.7; 95% CI 1.4 to 2.0; p<0.001). Unlike the predictors of death, all variables included into multivariable model were not significantly associated with treatment failure.ConclusionIn the past 10 years, although MDR-TB treatment success in Ethiopia has been consistently favourable, the proportion of patients who died is still considerable. Death could be attributed to advanced age, HIV infection and anaemia. Prospective cohort studies are necessary to further explore the potentially modifiable predictors of treatment failure.

Author(s):  
Abudl Wahid ◽  
Nafees Ahmad ◽  
Abdul Ghafoor ◽  
Abdullah Latif ◽  
Fahad Saleem ◽  
...  

In Pakistan, the treatment of multidrug-resistant tuberculosis (MDR-TB) with a shorter treatment regimen (STR), that is, 4–6 months of amikacin, moxifloxacin (Mfx), ethionamide, clofazimine (Cfz), pyrazinamide (Z), ethambutol (E), and high-dose isoniazid, followed by 5 months of Mfx, Cfz, Z, and E, was initiated in 2018. However, there is a lack of information about its effectiveness in Pakistani healthcare settings. Therefore, this retrospective record review of MDR-TB patients treated with STR at eight treatment sites in Pakistan aimed to fill this gap. Data were analyzed using SPSS 23. Multivariate binary logistic regression (MVBLR) analysis was conducted to find factors associated with death and treatment failure, and lost to follow-up (LTFU). A P-value < 0.05 was considered statistically significant. Of 912 MDR-TB patients enrolled at the study sites, only 313 (34.3%) eligible patients were treated with STR and included in the current study. Of them, a total of 250 (79.9%) were cured, 12 (3.8%) completed treated, 31 (9.9%) died, 16 (5.1%) were LTFU, and four (1.3%) were declared as treatment failures. The overall treatment success rate was 83.7%. In MVBLR analysis, patients’ age of 41–60 (odds ratio [OR] = 4.9, P-value = 0.020) and > 60 years (OR = 3.6, P-value = 0.035), being underweight (OR = 2.7, P-value = 0.042), and previous TB treatment (OR = 0.4, P-value = 0.042) had statistically significant association with death and treatment failure, whereas patients’ age of > 60 years (OR = 5.4, P-value = 0.040) and previous TB treatment (OR = 0.2, P-value = 0.008) had statistically significant association with LTFU. The treatment success rate of STR was encouraging. However, to further improve the treatment outcomes, special attention should be paid to the patients with identified risk factors.


2016 ◽  
Vol 60 (8) ◽  
pp. 4786-4792 ◽  
Author(s):  
Xubin Zheng ◽  
Rongrong Zheng ◽  
Yi Hu ◽  
Jim Werngren ◽  
Lina Davies Forsman ◽  
...  

ABSTRACTOur study aims to identify the clinical breakpoints (CBPs) of second-line drugs (SLDs) above which standard therapy fails in order to improve multidrug-resistant tuberculosis (MDR-TB) treatment. MICs of SLDs were determined forM. tuberculosisisolates cultured from 207 MDR-TB patients in a prospective cohort study in China between January 2010 and December 2012. Classification and regression tree (CART) analysis was used to identify the CBPs predictive of treatment outcome. Of the 207 MDR-TB isolates included in the present study, the proportion of isolates above the critical concentration recommended by WHO ranged from 5.3% in pyrazinamide to 62.8% in amikacin. By selecting pyrazinamide as the primary node (CBP, 18.75 mg/liter), 72.1% of sputum culture conversions at month four could be predicted. As for treatment outcome, pyrazinamide (CBP, 37.5 mg/liter) was selected as the primary node to predict 89% of the treatment success, followed by ofloxacin (CBP, 3 mg/liter), improving the predictive capacity of the primary node by 10.6%. Adjusted by identified confounders, the CART-derived pyrazinamide CBP remained the strongest predictor in the model of treatment outcome. Our findings indicate that the critical breakpoints of some second-line drugs and PZA need to be reconsidered in order to better indicate MDR-TB treatment outcome.


2019 ◽  
Author(s):  
Le Hong Van ◽  
Phan Trieu Phu ◽  
Dao Nguyen Vinh ◽  
Vo Thanh Son ◽  
Nguyen Thi Hanh ◽  
...  

Abstract Background: Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcome. Predictors of poor outcomes vary in different regions. Vietnam is among the 30 countries with high burden of MDR-TB. We aim to describe demographic characteristics and identify risk factors for poor outcome of MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam. Methods: This retrospective study included 2,266 patients who initiated MDR-TB treatment from 2011 to 2015 in HCMC. Treatment outcomes were available in 2,240 patients. Data was collected from standardized paper-based treatment cards and electronic records. Kruskal Wallis test was used to diagnose the change of median of age and body mass index (BMI) over 5 years, and Wilcoxon test to compare median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression on multiple imputation was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program. Results: Among 2,266 eligible cases, 60.2% were failure of category I or II regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. Notification rate increased 24.7% from 2011 to 2015.Treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty and 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1kg/m2 of BMI for patients with BMI<21). Conclusion: Our study describes the increasing cases of MDR-TB in HCMC during 2011 to 2015. Patients with HIV, high smear grade, malnutrition and history of previous MDR-TB treatment should receive additional care. Keywords: multidrug resistant tuberculosis; retrospective; treatment outcome; risk factors; Vietnam


2019 ◽  
Author(s):  
Alhassane Diallo ◽  
Boubacar Djelo Diallo ◽  
Lansana Mady Camara ◽  
Lucrèce Ahouéfa Nadège Kounoudji ◽  
Boubacar Bah ◽  
...  

Abstract Background Despite the predictor role of the body weight variation on multidrug-resistant tuberculosis (MDR-TB) treatment outcome, little data are available to corroborate this finding. We aimed to study the course of weight in patients with MDR-TB, to identify subgroups of weight evolutions, and to determine factors that influence these evolutions.Methods Patients treated with a shorter MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 from three major drug-resistance TB centres in Guinea, who had rifampicin resistance, and who were cured or died were analysed. Patients were seen monthly until the end of treatment. Clinical outcome was the Body Mass Index (BMI). We used a linear mixed model to analyze the course of BMI and a latent class mixed model to identify subgroup of BMI evolutions.Results Of 232 patients treated for MDR-TB during the study period, 165 (71%) were analysed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 – 8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m 2 . Factors that associated with faster BMI progression were cured to MDR-TB treatment (0.24 [SE 0.09] per kg/m 2 ; p = 0.0205), and the absence of lung cavities on X-ray (0.18 [0.06] per kg/m 2 ; p = 0.0068). Two subgroups of BMI evolution were identified: “Rapid BMI (n = 121; 85%) and “Slow BMI evolution (n = 22; 15%). Patients in the slow increasing BMI group were mostly female (68%) without history of TB treatment (41%) with most severe clinical condition at baseline, characterized by a higher frequency of symptoms including HIV infection (59%), depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelets count, and higher liver SGOT count. These patients had also a longer time to-initial culture conversion delay (log-rank test: p = 0.0087).Conclusion The available data provide quantitative information on BMI progression of patients with MDR-TB treated with a shorter regimen, and allowed the identification of the subgroup of patients with different BMI evolutions. Furthermore, they emphasize the usefulness of BMI as biomarker to monitor MDR-TB treatment outcome.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255357
Author(s):  
Nguyen Bao Ngoc ◽  
Hoa Vu Dinh ◽  
Nguyen Thi Thuy ◽  
Duong Van Quang ◽  
Cao Thi Thu Huyen ◽  
...  

Objective Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. Method We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. Results Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91–37.42]), renal dysfunction (HR = 8.46 [1.91–37.42]), alcoholism (HR = 13.28 [5.04–34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14–1.43]). Conclusion While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.


Biomédica ◽  
2020 ◽  
Vol 40 (4) ◽  
pp. 616-625
Author(s):  
Ángela Tobón ◽  
Johana Rueda ◽  
Diego H. Cáceres ◽  
Gloria I. Mejía ◽  
Elsa M. Zapata ◽  
...  

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.


2020 ◽  
Author(s):  
Alhassane Diallo ◽  
Boubacar Djelo Diallo ◽  
Lansana Mady Camara ◽  
Lucrèce Ahouéfa Nadège Kounoudji ◽  
Boubacar Bah ◽  
...  

Abstract Background: Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. Methods: We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. Results: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 – 8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m 2 . Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m 2 ; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m 2 ; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0087). Conclusion: Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.


2020 ◽  
pp. 00537-2020
Author(s):  
Philipp du Cros ◽  
Khamraev Atadjan ◽  
Tigay Zinaida ◽  
Tleubergen Abdrasuliev ◽  
Jane Greig ◽  
...  

BackgroundIn 2016, WHO guidelines conditionally recommended standardised shorter 9–12 month regimens for multidrug-resistant tuberculosis (MDR-TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.MethodsConsecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between 1st September 2013 and 31st March 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.ResultsOf 146 enrolled, 128 patients were included: 67 female (52.3%), median age 30.1 (IQR 23.8–44.4) years. At the end of treatment, 71.9% (92/128) patients achieved treatment success, with 68% (87/128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failure with fluoroquinolone resistance amplification in 8 patients (8/22, 36.4%); 12 (9.4%) loss to follow-up; 2 (1.5%) deaths. Recurrence occurred in one patient. 14 patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (aOR 6.13, 95% CI 2.01;18.63) and adherence<95% (aOR 5.33, 95% CI 1.73;16.36) were associated with unsuccessful outcome in multivariable logistic regression.ConclusionsOverall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of DST-confirmed susceptibility.


2020 ◽  
Author(s):  
Alhassane Diallo ◽  
Boubacar Djelo Diallo ◽  
Lansana Mady Camara ◽  
Lucrèce Ahouéfa Nadège Kounoudji ◽  
Boubacar Bah ◽  
...  

Abstract Background: Despite the predictor role of the body weight variation on multidrug-resistant tuberculosis (MDR-TB) treatment outcome, little data are available to corroborate this finding. We aimed to study the course of weight in patients with MDR-TB, to identify subgroups of weight evolutions, and to determine factors that influence these evolutions. Methods: Patients treated with a shorter MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 from three major drug-resistance TB centers in Guinea, who had rifampicin resistance, and who were cured or died were analyzed. Patients were seen monthly until the end of treatment. Clinical outcome was the Body Mass Index (BMI). We used a linear mixed model to analyze the course of BMI and a latent class mixed model to identify subgroup of BMI evolutions. Results: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 – 8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m 2 . Factors that associated with faster BMI progression were cured to MDR-TB treatment (0.24 [SE 0.09] per kg/m 2 ; p = 0.0205), and the absence of lung cavities on X-ray (0.18 [0.06] per kg/m 2 ; p = 0.0068). Two subgroups of BMI evolution were identified: “Rapid BMI (n = 121; 85%) and “Slow BMI evolution (n = 22; 15%). Patients in the slow increasing BMI group were mostly female (68%) without history of TB treatment (41%), with positive HIV infection (59%), with most severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelets count, and higher liver SGOT count. These patients had also a longer time to-initial culture conversion delay (log-rank test: p = 0.0087). Conclusion: The available data provided quantitative information on BMI progression of patients with MDR-TB treated with a shorter regimen, and allowed the identification of the subgroup of patients with different BMI evolutions. Furthermore, they emphasized the usefulness of BMI as biomarker to monitor MDR-TB treatment outcome.


2021 ◽  
Vol 45 ◽  
pp. 1
Author(s):  
Gloria Mercedes Puerto Castro ◽  
Fernando Nicolás Montes Zuluaga ◽  
Jacqueline Elizabeth Alcalde-Rabanal ◽  
Freddy Pérez

Objective. To identify patient- and provider-related factors associated with the success of multidrug-resistant tuberculosis (MDR-TB) treatment in the six municipalities of Colombia with the highest number of MDR-TB cases. Methods. Bivariate and multivariate logistic regressions were used to analyze the association between treatment success (cure or treatment completion) and characteristics of the patients and physicians, nursing professionals, and psychologists involved in their treatment. The importance of knowledge in the management of MDR-TB cases was explored through focus groups with these providers. Results. Of 128 cases of TB-MDR, 63 (49.2%) experienced treatment success. Only 52.9% of the physicians and nursing professionals had satisfactory knowledge about MDR-TB. Logistic regression showed that being HIV negative, being affiliated with the contributory health insurance scheme, being cared for by a male physician, and being cared for by nursing professionals with sufficient knowledge were associated with a successful treatment outcome (p ≤ 0.05). Qualitative analysis showed the need for in-depth, systematic training of health personnel who care for patients with MDR-TB. Conclusion. Some characteristics of patients and healthcare providers influence treatment success in MDR-TB cases. Physicians’ and nurses’ knowledge about MDR-TB must be improved, and follow-up of MDR-TB patients who are living with HIV and of those affiliated with the subsidized health insurance scheme in Colombia must be strengthened, as these patients have a lower likelihood of a successful treatment outcome.


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