scholarly journals Overcoming barriers to the access and uptake of newer drugs for multidrug-resistant TB

2020 ◽  
Vol 24 (10) ◽  
pp. 1054-1057
Author(s):  
I. Zabsonre ◽  
S. S. Thi ◽  
V. Cox

To improve the unsatisfactory treatment outcomes of multidrug-resistant TB (MDR-TB), it is essential we use new regimens based on newer drugs. To address challenges in the introduction of BDQ and the shorter treatment regimen (STR), the USAID has committed to support countries receiving BDQ (through the USAID/Janssen Bedaquiline Donation Program), with targeted short-term technical assistance (TA). Six MDR-TB clinical consultants were recruited and provided TA to 17 countries between 2017 and 2019. Building on other in-country support, this short-term TA proved instrumental in overcoming barriers, such as misconceptions about BDQ safety, inadequate clinical skills to manage patients and limited expansion plans to increase access to BDQ and the STR.

2020 ◽  
Vol 24 (2) ◽  
pp. 233-239
Author(s):  
S. Park ◽  
K-W. Jo ◽  
T. S. Shim

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.


2020 ◽  
Vol 114 (10) ◽  
pp. 733-741
Author(s):  
Muhammad Atif ◽  
Wajiha Ahmad ◽  
Nafees Ahmad ◽  
Iram Malik ◽  
Sajjad Sarwar

Abstract Background This study aims to evaluate the treatment outcomes and factors associated with unsuccessful treatment outcomes among multidrug-resistant TB (MDR-TB) patients. Method This was a retrospective observational study conducted at the Bahawal Victoria Hospital, Bahawalpur, Pakistan. The sociodemographic, clinical and treatment-related data of MDR-TB patients registered at the study site between June 2014 and December 2016 were retrospectively collected. Patients’ treatment outcomes were categorized on the basis of WHO-recommended criteria. Multivariate binary logistic regression analysis was used to find the independent factors associated with unsuccessful treatment outcomes. Results Out of 179 MDR-TB patients, 106 (59.2%) completed their treatment successfully. The remaining 73 patients (40.8%) had unsuccessful treatment outcomes, among whom 45 (25.1%) died, while 18 (10.1%) were lost to follow-up. Factors associated with unsuccessful treatment outcomes included age ≥40 y (AOR 4.310; p = 0.006), unsuccessful interim treatment outcomes (AOR 5.810; p = 0.032), occurrence of adverse events (AOR 0.290; p = 0.029) and ofloxacin resistance (AOR 2.952; p = 0.042). Conclusion The treatment success rate among the selected cohort of MDR-TB patients was less than the target of ≥75% set by the WHO in the End TB Strategy. The lower treatment success rate at the study site requires urgent attention from clinicians and program managers.


2020 ◽  
Vol 65 (1) ◽  
pp. e00744-20
Author(s):  
Martha L. van der Walt ◽  
Karen Shean ◽  
Piet Becker ◽  
Karen H. Keddy ◽  
Joey Lancaster

ABSTRACTTreatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.


2020 ◽  
Vol 24 (5) ◽  
pp. 485-491
Author(s):  
D. Butov ◽  
C. Lange ◽  
J. Heyckendorf ◽  
I. Kalmykova ◽  
T. Butova ◽  
...  

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.


2017 ◽  
Vol 49 (3) ◽  
pp. 1600803 ◽  
Author(s):  
Mayara Lisboa Bastos ◽  
Zhiyi Lan ◽  
Dick Menzies

This systematic review aimed to update the current evidence for multidrug-resistant tuberculosis (MDR-TB) treatment.We searched for studies that reported treatment information and clinical characteristics for at least 25 patients with microbiologically confirmed pulmonary MDR-TB and either end of treatment outcomes, 6-month culture conversion or severe adverse events (SAEs). We assessed the association of these outcomes with patients' characteristics or treatment parameters. We identified 74 studies, including 17 494 participants.The pooled treatment success was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. Treatment parameters such as number or duration and individual drugs were not associated with improved 6-month sputum culture conversion or end of treatment outcomes. However, MDR-TB patients that received individualised regimens had higher success than patients who received standardised regimens (64% versus 52%; p<0.0.01). When reports from 20 cohorts were pooled, proportions of SAE ranged from 0.5% attributed to ethambutol to 12.2% attributed to para-aminosalicylic acid. The lack of significant associations of treatment outcomes with specific drugs or regimens may reflect the limitations of pooling the data rather than a true lack of differences in efficacy of regimens or individual drugs.This analysis highlights the need for stronger evidence for treatment of MDR-TB from better-designed and reported studies.


2020 ◽  
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 outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with 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 between 2011-2015 in HCMC. Treatment outcomes were available for 2,240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program.Results: Among 2,266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011-2015. The 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 or 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: The number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011-2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.


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.


2021 ◽  
Author(s):  
Shao-Jun Zhang ◽  
Yan Yang ◽  
Wen-Wen Sun ◽  
Zhong-Shun Zhang ◽  
He-ping Xiao ◽  
...  

Abstract Objective: To compare the effectiveness and safety of bedaquiline-containing and bedaquiline-free regimens for treatment of patients with refractory rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB).Methods: Patients with refractory RR/MDR-TB receiving bedaquiline-containing regimens (bedaquiline group, n=102) and bedaquiline-free regimens (non-bedaquiline group, n=100) were included in this retrospective historical control study across East China. The culture conversion, end-of-treatment outcomes, cavity closing rate, and adverse events (AEs) were compared between the two groups. Univariate and multivariate analyses were performed to identify independent predictors of treatment success and culture reversion.Results: The baseline characteristics of the patients were well balanced between the two groups. The culture conversion rates in the bedaquiline group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs. 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs. 65.0%) were all significantly higher than those in the non-bedaquiline group (all p<0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs. 8.0%, p=0.017) and month 12 (39.2% vs. 15.0%, p<0.001). Patients receiving bedaquiline-containing regimens had more treatment success than those receiving bedaquiline-free regimens (p<0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%). The use of bedaquiline was identified as an independent predictor of both treatment success (OR=7.356, 95% CI: 2.920–18.530, p<0.001) and culture reversion (OR=0.124, 95% CI: 0.035–0.452, p<0.001). AEs were similarly reported in 26.5% of patients in the bedaquiline group and 19.0% in the non-bedaquiline group (p=0.206).Conclusions: Bedaquiline-containing regimens resulted in better treatment outcomes and similar safety relative to bedaquiline-free regimens for patients with refractory pulmonary RR/MDR-TB.


2020 ◽  
Vol 8 (4) ◽  
pp. 235-242
Author(s):  
C.A. Akinleye ◽  
A. Onabule ◽  
A.O. Oyekale ◽  
M.O. Akindele ◽  
O.J. Babalola ◽  
...  

Introduction: In Nigeria, patients accessing Directory Observed Therapy (DOTS) treatment are exposed to resistance to anti-TB drugs, hence is  considered a priority, only few studies have focused on the relevant risk factors, Factors leading to development of drug resistance need to be understood to develop appropriate control strategies for national programsMethod: The study was a cross sectional study design. Multistage sampling technique was employed in the selection of 403 tuberculosis patients in Ibadan North Local Government Area of Oyo State. Data were collected using self-administered structured questionnaire, and analyzed using SPSS version 25. Level of significance was set at P<0.05.Results: Fifty three (13.2%) of the total respondent had Multidrug Resistant TB (MDR-TB) which is more among the males 36(67.9%) (p>0.05). Education and Occupation shows a significant association with MDR-TB, (χ2=24.640, p =0.007) and (χ2=14.416, p = 0.006) respectively,risk factors such asprevious TB treatment and Adherence with treatment regimen (r=0.270, p<0.05), HIV (r=0.168, p<0.05) and smoking (ß=0.107, t=2.144, p<0.05) were statistically associated with development of acquired MDR-TB.Conclusion: This finding revealed that Previous TB treatment andAdherence with treatment regimen were found to be the major risk factor for MDR-TB. Targeted educational intervention for patients and their contacts may minimize the nonadherence with prescribed TB treatment and lessen MDR-TB magnitude. High quality directly observed treatment should be strengthened to ensure that the previously treated patients can receive standard and regular regimens. Keywords: TB Patients, MDR-TB, tuberculosis, Risk factors.   French Title: Facteurs de risque associés à la MDR-TB parmi les patientstuberculeux à Ibadan, état d'Oyo, Nigéria Introduction: Au Nigéria, les patients accédant au traitement DOTS (Directory Observed Therapy) sont exposés à une résistance aux médicaments  antituberculeux, ce qui est considéré comme une priorité, seules quelques études se sont concentrées sur les facteurs de risque pertinents. Les facteurs menant au développement d'être compris pour développer des stratégies de contrôle appropriées pour les programmes nationaux.Méthode de l'étude: L'étude était un plan d'étude transversale. Une technique d'échantillonnage à plusieurs degrés a été utilisée pour  sélectionner 403 patients tuberculeux dans la région du gouvernement local d'Ibadan Nord de l'état d'Oyo. Les données ont été collectées à l'aide d'un questionnaire structuré auto-administré et analysées à l'aide de la version 25 du SPSS. Le niveau de signification a été fixé à P <0,05.Résultats de l'étude: Cinquante-trois (13,2%) des répondants totaux avaient une tuberculose multi résistante (MDR-TB), ce qui est plus parmi les hommes 36 (67,9%) (p> 0,05). L'éducation et la profession montrent une association significative avec la TB-MR, (χ2 = 24,640, p = 0,007) et (χ2 = 14,416, p = 0,006) respectivement, des facteurs de risque tels que le traitement antituberculeux antérieur et l'observance du schéma thérapeutique (r =0,270, p <0,05), le VIH (r = 0,168, p <0,05) et le tabagisme (ß = 0,107, t = 2,144, p <0,05) étaient statistiquement associés au développement de la TB-MR acquise.Conclusion: Ce résultat a révélé que le traitement antituberculeux antérieur et l'observance du schéma thérapeutique étaient les principaux  facteurs de risque de TB-MR. Une intervention éducative ciblée pour les patients et leurs contacts peut minimiser la non-observance du traitement antituberculeux prescrit et réduire l'ampleur de la TB-MR. Un traitement de haute qualité directement observé doit être renforcé pour garantir queles patients précédemment traités puissent recevoir des schémas standards et réguliers. Mots-clés: Patients TB, MDR-TB, tuberculose, facteurs de risque  


2019 ◽  
Author(s):  
Elvis Dzelamonyuy Chem ◽  
Marie Claire Van Hout ◽  
Vivian Hope

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) in HIV endemic settings is a major threat to public health. MDR-TB is a substantial and underreported problem in Sub-Saharan Africa (SSA), with recognised cases projected to increase with advancement in diagnostic technology. There is paucity of review evidence on treatment outcomes and antiretroviral (ART) uptake among MDR-TB patients with HIV in SSA. To address this gap a review of treatment outcomes in HIV patients co-infected with MDR-TB in the SSA region was undertaken. Methods Three databases (Medline, Web of Science, CINHAL), Union on Lung Heath conference proceedings and grey literature were searched for publications between January 2004 and May 2018. Records were assessed for eligibility and data extracted. Random effect meta-analysis was conducted using STATA and Cochrane’s review manager. Results A total of 271 publications were identified of which nine fulfilled the inclusion criteria. Data was collected from 3,368 MDR-TB and HIV co-infected patients from four SSA countries; South Africa (6), Lesotho (1), Botswana (1) and Ethiopia (1). The most common outcome was cure (34.9% cured in the pooled analysis), this was followed by death (18.1% in pooled analysis). ART uptake was high, at 83% in the pooled analysis. Cure ranged from 22.2% to 57.7% among patients on ART and from 28.6% to 54.7% among those not on ART medication. MDR-TB and HIV coinfected patients were less likely to be successfully treated than HIV negative MDR-TB patients (Risk Ratio = 0.87, 95% CI 0.97, 0.96). Conclusion Treatment outcomes for MDR-TB and HIV coinfected patients do not vary widely from those reported globally. However, treatment success was lower among HIV positive MDR-TB patients compared to HIV negative MDR-TB patients. Prompt antiretroviral initiation and interventions to improve treatment adherence are necessary.


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