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.

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.

scholarly journals Assessing the impacts of short-course multidrug-resistant tuberculosis treatment in the Southeast Asia Region using a mathematical modeling approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248846
Author(s):  
Win Min Han ◽  
Wiriya Mahikul ◽  
Thomas Pouplin ◽  
Saranath Lawpoolsri ◽  
Lisa J. White ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Treatment Initiation ◽  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb ◽  
The Impact

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221–275) per 100,000 population in 2020 to 239 (95% CrI, 215–267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%–2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1–2.9) in 2020 and 2.5% (95% CrI, 2.3–3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9–41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9–40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region.

scholarly journals Active surveillance for adverse events in patients on longer treatment regimens for multidrug-resistant tuberculosis in Viet Nam

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 ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Bayesian Model Averaging ◽  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

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.

scholarly journals Revolutionary new treatment regimens for multidrug-resistant tuberculosis

2019 ◽  
Vol 19 (3) ◽  
pp. 233-234 ◽  
Author(s):  
Timothy D McHugh ◽  
Isobella Honeyborne ◽  
Marc Lipman ◽  
Alimuddin Zumla
Keyword(s):  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
New Treatment

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 &gt;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.

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 Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate of Mycobacterium tuberculosis in patients with multidrug-resistant tuberculosis in Tanzania

2020 ◽  
Author(s):  
Peter M. Mbelele ◽  
Emmanuel A. Mpolya ◽  
Elingarami Sauli ◽  
Bariki Mtafya ◽  
Nyanda E. Ntinginya ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Bacterial Load ◽  
Elimination Rate ◽  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Mixed Effects Modeling ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

AbstractBackgroundRifampin or multidrug-resistant-tuberculosis (RR/MDR-TB) treatment has transitioned to injectable-free regimens. We tested whether M. tuberculosis (Mtb) elimination rates measured by molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB antibiotic regimen.MethodsSerial sputa were collected from patients with RR/MDR- and drug-sensitive TB at day 0, 3, 7, 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viable Mtb 16S rRNA in sputum for estimation of colony-forming-unit per mL (eCFU/mL). Mtb elimination rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures.ResultsAmong 37 patients with a total of 296 serial sputa; 7 patients received rifampin/isoniazid/pyrazinamide/ethambutol (RHZE), 8 an all-oral bedaquiline-based regimen, 9 an injectable and bedaquiline-containing regimen, and 13 an injectable-containing but bedaquiline-free regimen. The overall mean daily Mtb elimination was −0.24 [95% Confidence-Interval (CI); −0.39 to −0.08)] log10 eCFU/mL, and it varied with treatment-regimen (p < 0.001). Compared to the adjusted Mtb elimination of −0.17 (95% CI; −0.23 to −0.12) for the injectable-containing but bedaquiline-free reference regimen, the elimination rates were −0.62 (95% CI; −1.05 to −0.20) log10 eCFU/mL for the injectable and bedaquiline-containing regimen (p = 0.019), −0.35 (95% CI; −0.65 to −0.13) log10 eCFU/mL for the all-oral bedaquiline-based regimen (p = 0.054), and −0.29 (95% CI; −0.78 to +0.22) log10 eCFU/mL for RHZE (p = 0.332)ConclusionTB-MBLA distinguished Mtb elimination rates in sputa from patients receiving different treatment regimens, suggesting a reliable monitoring tool for RR/MDR-TB, that does not require mycobacterial culture.

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 Multi-drug resistant tuberculosis burden and risk factors: An update

1970 ◽  
Vol 8 (1) ◽  
pp. 116-125 ◽  
Author(s):  
SB Marahatta
Keyword(s):  
Risk Factors ◽  
Treatment Strategies ◽  
Multidrug Resistant ◽  
Inverse Association ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Resource Poor ◽  
Mdr Tb

Multi-drug resistant (MDR) tuberculosis is defined as disease caused by Mycobacterium tuberculosis with resistance to at least two anti-tubercular drugs Isoniazid and Rifampicin. Recent surveillance data have revealed that prevalence of the drug resistant tuberculosis has risen to the highest rate ever recorded in the history. Drug resistant tuberculosis generally arises through the selection of mutated strains by inadequate therapy. The most powerful predictor of the presence of MDR-TB is a history of treatment of TB. Shortage of drugs has been one of the most common reasons for the inadequacy of the initial anti-TB regimen, especially in resource poor settings. Other major issues significantly contributing to the higher complexity of the treatment of MDR-TB is the increased cost of treatment. Other factors also play important role in the development of MDR-TB such as poor administrative control on purchase and distribution of the drugs with no proper mechanism on quality control and bioavailability tests. Tuberculosis control program implemented in past has also partially contributed to the development of drug resistance due to poor follow up and infrastructure. The association known for centuries between TB and poverty also applies to MDR-TB, a rather significant inverse association with MDR-TB. Various treatment strategies have been employed, including the use of standardised treatment regimens based upon representative local susceptibility patterns, empirical treatment based upon previous treatment history and local Drug Susceptibility Test (DST) patterns, and individualised treatment designed on the basis of individual DST results. Treatment outcomes among MDR-TB cases have varied widely; a recent survey of five Green Line Committee (GLC) approved sites in resource-limited countries found treatment success rates of 70%. Treatment continues to be limited in the resource poor countries where the demand is high. The ultimate strategy to control multidrug resistant tuberculosis is one that implements comprehensive approach incorporating treatment of multidrug-resistant tuberculosis based upon principles closely related to those of its general DOTS strategy for TB control: sustained political commitment; a rational case-finding strategy including accurate, timely diagnosis through quality assured culture and DST; appropriate treatment strategies that use second-line drugs under proper case management conditions; uninterrupted supply of quality-assured antituberculosis drugs; standardised recording and reporting system. Key words: DOTS Plus; Multi drug resistant (MDR) tuberculosis burden; risk factors. DOI: 10.3126/kumj.v8i1.3234 Kathmandu University Medical Journal (2010), Vol. 8, No. 1, Issue 29, 116-125

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