scholarly journals Immunomodulatory agents combat multidrug-resistant tuberculosis by improving antimicrobial immunity

2021 ◽  
Author(s):  
Jagadeeswara Rao Muvva ◽  
Sultan Ahmed ◽  
Rokeya Sultana Rekha ◽  
Sadaf Kalsum ◽  
Ramona Groenheit ◽  
...  
Keyword(s):  
Treatment Options ◽  
Treatment Success ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Success Rates ◽  
Immunomodulatory Agents ◽  
Human Macrophages ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) has low treatment success rates and new treatment strategies are needed. We explored if treatment with vitamin D (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis. Methods A clinically relevant model was used consisting of human macrophages infected with M. tuberculosis-isolates (n=15) with different antibiotic-resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), mRNA expression analyses (LL-37, β-defensin, nitric oxide synthase, and dual oxidase-2), RNA interference (LL-37-silencing in primary macrophages), western blot and confocal microscopy (LL-37 and LC3 protein expression). Results VitD+PBA inhibited growth of clinical MDR-TB strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and LC3-dependent autophagy. Gene-silencing of LL-37 expression enhanced MDR-TB growth in vitD+PBA-treated macrophages. The combination of vitD+PBA and isoniazid were equally effective to reduce intracellular MDR-TB growth as compared to a >125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid. Conclusions Immunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR-TB treatment and contribute to next-generation individualized treatment options for difficult-to-treat pulmonary TB patients.

Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

2020 ◽  
Vol 24 (2) ◽  
pp. 233-239
Author(s):  
S. Park ◽  
K-W. Jo ◽  
T. S. Shim
Keyword(s):  
Success Rate ◽  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Treatment Success Rate ◽  
Aminosalicylic Acid ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Effective Drugs

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.

scholarly journals Epidemiology of drug-resistant tuberculosis in Chongqing, China: a retrospective observational study from 2010 to 2017

2019 ◽  
Author(s):  
Bo Wu ◽  
Ya Yu ◽  
Changting Du ◽  
Ying Liu ◽  
Daiyu Hu
Keyword(s):  
Observational Study ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Policy Support ◽  
Retrospective Observational Study ◽  
Drug Resistant ◽  
Notification Rate ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

AbstractChina is one of the top 30 countries with high multidrug-resistant tuberculosis (MDR-TB) and rifampin-resistant tuberculosis (RR-TB) burden. Chongqing is a southwest city of China with a large rural population. A retrospective observational study has been performed based on routine tuberculosis (TB) surveillance data in Chongqing from 2010 to 2017. The MDR/RR-TB notification rate increased from 0.03 cases per 100,000 population in 2010 to 2.09 cases per 100,000 population in 2017. The extensively drug-resistant TB (XDR-TB) notification rate has increased to 0.09 cases per 100,000 population in 2017. There was a decreasing detection gap between the number of notified MDR/RR-TB cases and the estimate number of MDR/RR-TB cases among all notified TB cases. The treatment success rate of MDR/RR-TB was 50.66% in this period. The rate of MDR/RR-TB in new TB cases was 6.23%, and this rate in previously treated TB cases was 32.7%. Despite the progress achieved, the prevalence of MDR/RR-TB was still high facing challenges including detection gaps, the regional disparity, and the high risk for MDR/RR-TB in elderly people and farmers. Sustained government financing and policy support should be guaranteed in the future.

scholarly journals Effectiveness of Shorter Treatment Regimen in Multidrug-Resistant Tuberculosis Patients in Pakistan: A Multicenter Retrospective Record Review

2021 ◽  
Author(s):  
Abudl Wahid ◽  
Nafees Ahmad ◽  
Abdul Ghafoor ◽  
Abdullah Latif ◽  
Fahad Saleem ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Success Rate ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Retrospective Record Review ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Record Review

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.

scholarly journals Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis.

Biomédica ◽  
2020 ◽  
Vol 40 (4) ◽  
pp. 616-625
Author(s):  
Ángela Tobón ◽  
Johana Rueda ◽  
Diego H. Cáceres ◽  
Gloria I. Mejía ◽  
Elsa M. Zapata ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Chronic Obstructive ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Poor Outcomes ◽  
Lost To Follow Up

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.

scholarly journals Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials

2016 ◽  
Vol 25 (139) ◽  
pp. 29-35 ◽  
Author(s):  
Riya Moodley ◽  
Thomas R. Godec
Keyword(s):  
Treatment Options ◽  
Standard Of Care ◽  
Multidrug Resistant ◽  
World Health ◽  
Efficacy And Safety ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization ◽  
Stage 1

Multidrug-resistant (MDR) tuberculosis (TB) is a threat to global TB control, as suboptimal and poorly tolerated treatment options have resulted in largely unfavourable outcomes for these patients. The last of six cohort studies conducted in Bangladesh which assessed a new shorter regimen using currently available TB drugs showed promising results and offered the possibility of a more acceptable and more effective regimen than the one recommended by the World Health Organization (WHO). The aims of stage 1 of the STREAM (Evaluation of a Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) trial are to evaluate the efficacy and safety of this regimen, compared to the current WHO-recommended standard of care. Stage 2 evaluates two new bedaquiline-containing regimens: one an all-oral regimen and the second a further shortened and simplified version of the stage 1 study regimen, comparing the efficacy and safety of each to that of the stage 1 study regimen and also to the WHO-recommended standard of care. Success of the stage 1 study regimen would in all probability provide a new standard of care for MDR-TB patients, while positive results from the bedaquiline-containing regimens in stage 2 may allow for even greater progress in the management of this difficult population.

scholarly journals Effectiveness and Safety of Bedaquiline-containing Regimens for Treatment on Patients With Refractory Rifampicin/multidrug-resistant Tuberculosis: A Retrospective Cohort Study in East China

2021 ◽  
Author(s):  
Shao-Jun Zhang ◽  
Yan Yang ◽  
Wen-Wen Sun ◽  
Zhong-Shun Zhang ◽  
He-ping Xiao ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
East China ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Conversion Rates ◽  
Mdr Tb ◽  
Culture Conversion ◽  
Closing Rate

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.

scholarly journals Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis

2016 ◽  
Vol 49 (1) ◽  
pp. 1600993 ◽  
Author(s):  
Greg J. Fox ◽  
Andrea Benedetti ◽  
Helen Cox ◽  
Won-Jung Koh ◽  
Piret Viiklepp ◽  
...  
Keyword(s):  
Individual Patient Data ◽  
Meta Analysis ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Patient Data ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Amoxicillin Clavulanic Acid ◽  
Group 5

The role of so-called “group 5” second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1–6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

Progress in global rollout of new multidrug-resistant tuberculosis treatments

2019 ◽  
Vol 23 (9) ◽  
pp. 996-999 ◽  
Author(s):  
K. Held ◽  
S. McAnaw ◽  
C-Y. Chiang ◽  
A. Trebucq ◽  
C. R. Horsburgh
Keyword(s):  
Treatment Strategies ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Internet Survey ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Global Increase ◽  
New Treatment

SETTING: The global multidrug-resistant tuberculosis (MDR-TB) epidemic has grown over the past decade and continues to be difficult to manage. In response, new drugs and treatment regimens have been recommended.OBJECTIVE: In 2017 and again in 2018, the International Union Against Tuberculosis and Lung Disease (The Union) drug-resistant (DR) TB Working Group collaborated with RESIST-TB to implement an internet survey to members of The Union around the world to assess access to these new treatment strategies.DESIGN: A nine-question survey was developed using SurveyMonkey®. The survey was open for participation to all members of The Union registered under the TB Section. Two reminders were sent during each survey. The responses were analyzed taking into account the WHO Region to which the respondent belonged.RESULTS: The 2018 survey showed a global increase in implementation of the shorter (9-month) MDR-TB regimen (from 33% to 56% of respondents, P < 0.001) and an increase in the use of bedaquiline and/or delamanid (from 25% to 41% of respondents, P < 0.001) compared to 2017. There were substantial variations in roll-out between WHO regions.CONCLUSION: These results demonstrate improvement in global implementation of the new treatment strategies over a 1-year period.

Compassionate Use of Delamanid in Adults and Children for Drug-resistant TB: 5-year Update

2020 ◽  
pp. 2002483
Author(s):  
Sambuddha Ghosh ◽  
Lusine Breitscheidel ◽  
Natasa Lazarevic ◽  
Alexandra Martin ◽  
Jeffrey Hafkin ◽  
...  
Keyword(s):  
Safety Profile ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Compassionate Use ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Qt Interval Prolongation ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

BackgroundAlthough delamanid has been approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in numerous regions, in areas where it is not yet registered, it can be accessed as part of salvage therapy—in particular, for those patients with limited treatment options—via the Otsuka Compassionate Use (CU) programme. Here we present the analysis of interim treatment outcomes by 24 weeks of more than 200 multidrug-resistant tuberculosis (MDR-TB) patients globally who received delamanid under the Otsuka CU programme.MethodsWe evaluated the treatment efficacy, with respect to culture negativity at 24 weeks, and safety profile of delamanid in a MDR-TB cohort of patients treated under CU between 2014 and 2019.ResultsAmong patients who received delamanid as part of a multidrug regimen, 123/202 (61%) had extensively drug-resistant tuberculosis (XDR-TB), 66/202 (33%) had HIV co-infection, and 34/202 (17%) were children ages between 6 and 17 years. Of those patients who were culture positive at delamanid treatment initiation and completed 24 weeks of delamanid treatment in combination with other anti-TB drugs, culture negativity was achieved in 116/147 (79%). The corresponding rates of culture negativity for patients with XDR-TB, HIV co-infection, and the paediatric subgroup were 69/90 (77%), 44/48 (92%), and 20/25 (80%), respectively. QT interval prolongation was the most frequently observed serious adverse event (reported in 8% of patients receiving delamanid). Overall, treatment safety outcomes did not reveal any new or unidentified risks.ConclusionsThe use of delamanid combined with other active drugs has the potential to achieve high rates of culture negativity in difficult-to-treat drug-resistant tuberculosis cases, with a favourable safety profile.

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