scholarly journals Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Myungsun Lee ◽  
Jeongha Mok ◽  
Deog Kyeom Kim ◽  
Tae Sun Shim ◽  
Won-Jung Koh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Study Protocol ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Tuberculosis Treatment ◽  
Open Label ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium

2019 ◽  
Vol 23 (10) ◽  
pp. 1050-1054
Author(s):  
L. Guglielmetti ◽  
J. Jaffré ◽  
C. Bernard ◽  
F. Brossier ◽  
N. El Helali ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Advisory Committees ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

Evaluation of 123 Cases with MDR TB (Multidrug Resistant Tuberculosis) Treatment

2018 ◽  
Author(s):  
Aylin Babalık ◽  
Ayse Rumeysa Hazine ◽  
Gul Erdal Donmez ◽  
Olga Akkan ◽  
Fatma Kutluhan ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Tuberculosis Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

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.

Management of Multidrug-Resistant Tuberculosis

2018 ◽  
Vol 39 (03) ◽  
pp. 310-324 ◽  
Author(s):  
Jose Caminero ◽  
Charles Daley
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Resistant Strains ◽  
Health Organization ◽  
Drug Resistant Strains

AbstractDrug-resistant strains of Mycobacterium tuberculosis pose a major threat to global tuberculosis control. Despite the availability of curative antituberculosis therapy for nearly half a century, inappropriate and inadequate treatment of tuberculosis, as well as unchecked transmission of M. tuberculosis, has resulted in alarming levels of drug-resistant tuberculosis. The World Health Organization (WHO) estimates that there were 600,000 cases of multidrug-resistant tuberculosis (MDR-TB)/rifampin-resistant (RR) tuberculosis in 2016, defined as strains that are resistant to at least isoniazid and rifampicin. Globally, WHO estimates that 4.1% of new tuberculosis cases and 19% of retreatment cases have MDR-TB. By the end of 2016, 123 countries had reported at least one case of extensively drug-resistant strains, which are MDR-TB strains that have acquired additional resistance to fluoroquinolones and at least one second-line injectable. It is estimated that only 22% of all MDR-TB cases are currently receiving therapy. This article reviews the management of MDR/RR-TB and updates recommendations regarding the use of shorter course regimens and new drugs.

scholarly journals Phase 2b Open-label Randomized Controlled Trial to Evaluate the Efficacy, Safety and Tolerability of N-acetylcysteine in Reducing Adverse Drug Reactions among Adults Treated for Multidrug-resistant Tuberculosis in Tanzania. (Trial Acronym NAC Trial).

2021 ◽  
Author(s):  
Stellah George George Mpagama ◽  
Happiness C Mvungi ◽  
Peter M Mbelele ◽  
Hadija H Semvua ◽  
Alphonce A Liyoyo ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Multidrug Resistant ◽  
Second Line ◽  
Drug Reactions ◽  
Open Label ◽  
Randomized Controlled ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background: Adverse drug reactions (ADRs) frequently occur in patients using second-line anti-tuberculosis medicine for treatment of multidrug resistant tuberculosis (MDR-TB). ADRs contribute to treatment interruptions which can compromise treatment response and risk acquired drug resistance to critical newer drugs such as bedaquiline, while severe ADRs carry considerable morbidity and mortality . N-acetylcysteine (NAC) has shown promise in reducing ADRs for medications related to TB in case series or randomized controlled trials in other medical conditions. We therefore designed a pilot clinical trial to study the protective effect of NAC among people treated for MDR-TB with second-line anti-TB medications. Methods: This is a phase 2b randomized open label clinical trial with 3 treatment arms including a control arm , an interventional arm of NAC 900mg daily , and an interventional arm of NAC 900mg twice-daily administered during the intensive phase of MDR-TB treatment. Patients initiating MDR-TB treatment will be enrolled at Kibong’oto National Center of Excellence for MDR-TB in the Kilimanjaro region of Tanzania . The minimum anticipated sample size is 66 ; with 22 participants in each arm. ADR monitoring will be performed at baseline and daily follow-up over 24 weeks including blood and urine specimen collection for hepatic and renal function and electrolyte abnormalities, and electrocardiogram. Sputum will be collected at baseline and monthly thereafter and cultured for mycobacteria as well as assayed for other molecular targets of Mycobacterium tuberculosis . Adverse drug events will be analysed over time using mixed effect models. Mean differences between arms in change of the ADRs from baseline (with 95% confidence intervals) will be derived from the fitted model. Discussion: Given that NAC promotes synthesis of glutathione, an intracellular antioxidant that combats the impact of oxidative stress , it may protect against medication induced oxidative damage in organs such as liver, pancreas, kidney and cells of the immune system. This randomized controlled trial will determine if NAC leads to fewer ADRs, and if this protection is dose dependent. Fewer ADRs among patients treated with MDR-TB may significantly improve treatment outcomes for multidrug regimens that necessitate prolonged treatment durations. Trial registration: PACTR202007736854169 Registered 03 July 2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12163

scholarly journals Aminoglycosides and Capreomycin in the Treatment of Multidrug-resistant Tuberculosis: Individual Patient Data Meta-analysis of 12 030 Patients From 25 Countries, 2009–2016

2020 ◽  
Author(s):  
J Peter Cegielski ◽  
Pei-Chun Chan ◽  
Zhiyi Lan ◽  
Zarir F Udwadia ◽  
Piret Viiklepp ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Individual Level ◽  
Injectable Drugs ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Standardized Treatment ◽  
Mdr Tb

Abstract Background As new drugs are developed for multidrug-resistant tuberculosis (MDR-TB), the role of currently used drugs must be reevaluated. Methods We combined individual-level data on patients with pulmonary MDR-TB published during 2009–2016 from 25 countries. We compared patients receiving each of the injectable drugs and those receiving no injectable drugs. Analyses were based on patients whose isolates were susceptible to the drug they received. Using random-effects logistic regression with propensity score matching, we estimated the effect of each agent in terms of standardized treatment outcomes. Results More patients received kanamycin (n = 4330) and capreomycin (n = 2401) than amikacin (n = 2275) or streptomycin (n = 1554), opposite to their apparent effectiveness. Compared with kanamycin, amikacin was associated with 6 more cures per 100 patients (95% confidence interval [CI], 4–8), while streptomycin was associated with 7 (95% CI, 5–8) more cures and 5 (95% CI, 4–7) fewer deaths per 100 patients. Compared with capreomycin, amikacin was associated with 9 (95% CI, 6–11) more cures and 5 (95% CI, 2–8) fewer deaths per 100 patients, while streptomycin was associated with 10 (95% CI, 8–13) more cures and 10 (95% CI, 7–12) fewer deaths per 100 patients treated. In contrast to amikacin and streptomycin, patients treated with kanamycin or capreomycin did not fare better than patients treated with no injectable drugs. Conclusions When aminoglycosides are used to treat MDR-TB and drug susceptibility test results support their use, streptomycin and amikacin, not kanamycin or capreomycin, are the drugs of choice.

scholarly journals Phase 2b open label randomized controlled trial to evaluate the efficacy, safety and tolerability of N-acetylcysteine in reducing adverse drug reactions among adults treated for multidrug-resistant tuberculosis in Tanzania. (Trial Acronym NAC Trial).

2021 ◽  
Author(s):  
Stellah Mpagama
Keyword(s):  
Controlled Trial ◽  
Multidrug Resistant ◽  
Second Line ◽  
Drug Reactions ◽  
Open Label ◽  
Randomized Controlled ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background: Adverse drug reactions (ADRs) frequently occur in patients using second-line anti-tuberculosis medicine for treatment of multidrug resistant tuberculosis (MDR-TB). ADRs contribute to treatment interruptions which can compromise treatment response and risk acquired drug resistance to critical newer drugs such as bedaquiline, while severe ADRs carry considerable morbidity and mortality. N-acetylcysteine (NAC) has shown promise in reducing ADRs for medications related to TB in case series or randomized controlled trials in other medical conditions. We therefore designed a pilot clinical trial to study the protective effect of NAC among people treated for MDR-TB with second-line anti-TB medications. Methods: This is a phase 2b randomized open label clinical trial with 3 treatment arms including a control arm, an interventional arm of NAC 900mg daily, and an interventional arm of NAC 900mg twice-daily administered during the intensive phase of MDR-TB treatment. Patients initiating MDR-TB treatment will be enrolled at Kibong’oto National Center of Excellence for MDR-TB in the Kilimanjaro region of Tanzania. The minimum anticipated sample size is 66; with 22 participants in each arm. ADR monitoring will be performed at baseline and regular follow-up over 24 weeks including blood and urine specimen collection for hepatic and renal function and electrolyte abnormalities, electrocardiogram and hearing function by pure tone audiometry. Sputum will be collected at baseline and monthly thereafter and cultured for mycobacteria as well as assayed for other molecular targets of Mycobacterium tuberculosis. Adverse drug events will be analyzed over time using mixed effect models. Mean differences between arms in change of the ADRs from baseline (with 95% confidence intervals) will be derived from the fitted model.Discussion: Given that NAC promotes synthesis of glutathione, an intracellular antioxidant that combats the impact of oxidative stress, it may protect against medication induced oxidative damage in organs such as liver, pancreas, kidney and cells of the immune system. This randomized controlled trial will determine if NAC leads to fewer ADRs, and if this protection is dose dependent. Fewer ADRs among patients treated with MDR-TB may significantly improve treatment outcomes for multidrug regimens that necessitate prolonged treatment durations.Trial registration: PACTR202007736854169

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