scholarly journals Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report

2019 ◽  
Vol 54 (6) ◽  
pp. 1901522 ◽  
Author(s):  
Sergey Borisov ◽  
Edvardas Danila ◽  
Andrei Maryandyshev ◽  
Margareth Dalcolmo ◽  
Skaidrius Miliauskas ◽  
...  
Keyword(s):  
Adverse Events ◽  
Active Drug ◽  
Clinical Information ◽  
World Health ◽  
Drug Resistant ◽  
Serious Adverse Events ◽  
Resistant Tuberculosis ◽  
Drug Safety Monitoring ◽  
Grade 3 ◽  
Health Organization

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

scholarly journals Incidence rate and time to serious adverse events among rifampicin resistant tuberculosis patients in Georgia treated with new and repurposed anti-tuberculosis drugs, 2016-2018

2021 ◽  
Vol 91 (1) ◽  
Author(s):  
Mariana Buziashvili ◽  
Hayk Davtyan ◽  
Yuliia Sereda ◽  
Olga Denisiuk ◽  
Ogtay Gozalov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Incidence Rate ◽  
Close Monitoring ◽  
Drug Resistant ◽  
Serious Adverse Events ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Drug Safety Monitoring ◽  
Treatment Safety

Considering the complexity of second-line anti-tuberculosis (TB) treatment regimens, the management of drug-resistant TB (DR-TB) in Georgia remains a major challenge. Since the introduction of new and repurposed anti-TB medications, the implementation of active TB Drug Safety Monitoring (aDSM) was a critical program component to help establish safety and manage all treatment related Serious Adverse Events (SAEs). In our study, we aimed to describe the occurrence, characteristics and timing of SAE among patients with Rifampicin Resistant and Multi-Drug Resistant TB (RR/MDR-TB) receiving new and/or repurposed anti-TB medications (bedaquiline, delamanid, linezolid, clofazimine, imipenem) during the period of 2016-2018 in Georgia and identify predictors of SAE. The data were obtained from the medical charts, electronic database and standardized aDSM reports During 2016-2018 period in total 970 people with RR/MDR-TB were notified in Georgia and 388 of them received new and/or repurposed TB drugs as part of their treatment regimen and all were included into the study. The results showed a total of 73 SAEs registered among 49 (12.6%) patients receiving new and/or repurposed drugs. The overall SAE incidence rate per 100 person-months was 1.16. The severity of the majority of the SAEs (46.6%) was grade III and 21.9% were grade IV. The most common SAE reported was hepatotoxicity, with an incidence of 0.26 per 100 person-month (n=16, 21.9%) followed by cardiotoxicity with an incidence of 0.16 per 100 person-month (n=10, 13.7%). Median time to SAE occurrence was 183 days (IQR 84 – 334) after treatment initiation. Resistance profile was the only predictor associated with occurrence of a SAEs. There was increased hazard of SAEs among patients with XDR-TB (adjusted HR=2.18, 95% CI: 1.12-4.23). Our findings on SAEs among patients treated with new or repurposed anti-TB drugs are echoing the findings available in the literature. They highlight the need for close monitoring of patients and underlines the importance of the aDSM during the whole treatment. Safety profile of the medications and combinations used are yet to be established and larger datasets comprised of patients receiving same treatment regimens need to be utilized.

scholarly journals Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jing-Tao Gao ◽  
Juan Du ◽  
Gui-Hui Wu ◽  
Yi Pei ◽  
Meng-Qiu Gao ◽  
...  
Keyword(s):  
Adverse Events ◽  
Multidrug Resistant ◽  
World Health ◽  
Chinese Patients ◽  
Prolonged Treatment ◽  
Drug Resistant ◽  
Aminosalicylic Acid ◽  
Clinical Patient ◽  
New Drug ◽  
Resistant Tuberculosis

Abstract Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

scholarly journals GeneXpert MTB/RIF Assay for Rapid Identification of Mycobacterium Tuberculosis and Rifampicin Resistance Directly from Sputum Sample

2017 ◽  
Vol 7 (2) ◽  
pp. 86-89 ◽  
Author(s):  
Nourjahan Laskar ◽  
Md Akram Hossain ◽  
Jannatul Fardows ◽  
Mominur Rahman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sputum Sample ◽  
Rapid Identification ◽  
Rapid Diagnosis ◽  
World Health ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
The World ◽  
Health Organization

Background: The World Health Organization has endorsed the use of molecular methods for the detection of tuberculosis (TB) and drug resistant TB as a rapid method. In Bangladesh, the Xpert MTB/RIF assay has been implemented into reference laboratories for diagnosis of TB and also MDR TB.Objective: Drug resistant tuberculosis has long been a common problem prevailing in our country. The present study focused on the rapid identification of Mycobacterium tuberculosis as well as drug resistance.Materials and Methods: Sputum samples from a total of 107 cases, assumed as multi-drug resistance tuberculosis, were studied through GeneXpert assay.Results: Out of 107 cases, 91 (85.05%) were detected having M. tuberculosis ? 64 (59.81%) were rifampicin sensitive and 27 (25.23%) were rifampicin resistant. The sensitivity and specificity of the GeneXpert are 87.64% and 75% respectively.Conclusion: GeneXpert assay can be considered for the rapid diagnosis of drug resistant tuberculosis.J Enam Med Col 2017; 7(2): 86-89

scholarly journals Effectiveness and safety of fully oral modified shorter treatment regimen for multidrug-resistant tuberculosis in Georgia, 2019-2020

2021 ◽  
Vol 91 (1) ◽  
Author(s):  
Teona Avaliani ◽  
Yuliia Sereda ◽  
Hayk Davtyan ◽  
Nestani Tukvadze ◽  
Tamar Togonidze ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Regimen ◽  
Treatment Success ◽  
World Health ◽  
Study Cohort ◽  
Hepatitis C Infection ◽  
Duration Of Treatment ◽  
Serious Adverse Events ◽  
Short Treatment ◽  
Resistant Tuberculosis

Tuberculosis treatment is challenging, especially among people with drug-resistant forms of tuberculosis. The introduction of fully oral modified short treatment regimen has a great potential to shorten duration of treatment, improve safety and ultimately increase treatment success rate. In 2019 Georgia has piloted the modified fully oral shorter treatment regimen in a routine programmatic condition. Our study aimed to evaluate effectiveness and safety of the modified shorter treatment regimen in Georgia among the first 25 consecutively enrolled patients with rifampicin-resistant tuberculosis with proven sensitivity to fluoroquinolone and without prior exposure to second-line tuberculosis drugs. Regimen consisted of 9-month daily administration of bedaquilline, linezolid, levofloxacin, clofazimine and cycloserine. Study patients were enrolled between March-August 2019. We used a national electronic surveillance system, medical records and active TB drug-safety monitoring and management database to extract study related data. The mean age of the study participants was 48 years, 68% were male, 8% were HIV positive, 16% had diabetes and 12% tested positive for hepatitis C infection. The median time to culture conversion among 16 patients who were culture positive at treatment initiation was 1.0 (95% CI: 1.0-2.0) month. Of those, by the end of treatment 15 patients converted to negative. Out of the 25 patients in the study cohort 22 (88%) had successful treatment outcome, one patient (4%) died and two (8%) were lost to follow up. The regimen was largely well tolerated. Three patients (12%) experienced serious adverse events, of which in two cases were possibly related to TB drugs in the regimen. Seven patients developed adverse events of interest in eight instances, including musculoskeletal (twice), psychiatric, gastrointestinal disorders, hepatotoxicity, peripheral neuropathy, cardiotoxicity and myelosuppression (once each). In four patients (16%) the duration of the treatment was extended beyond nine months due to insufficient radiological improvements. Our findings demonstrate that good treatment outcomes are achievable in people with fluoroquinolone-sensitive tuberculosis within routine programmatic conditions using fully oral modified short treatment regimen. The extensive use of fully oral modified shorter treatment regimen in Georgia and other high priority countries in the World Health Organization European Region is warranted.

scholarly journals Directrices unificadas de la OMS sobre el tratamiento de la tuberculosis farmacorresistente

2020 ◽  
Keyword(s):  
World Health Organization ◽  
Tuberculosis Treatment ◽  
World Health ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Health Organization

Estas directrices unificadas se han actualizado con arreglo a los procesos del grupo de elaboración de las directrices que se llevaron a cabo entre el 2011 y el 2018 de conformidad con los requisitos de la OMS. Este documento sustituye a otras recomendaciones de la OMS relativas al tratamiento de la tuberculosis (TB) multirresistente y resistente a la rifampicina (TB-MDR/RR) publicadas desde el 201. En este documento se incluyen las preguntas sobre población, intervención, comparador y resultado (PICO, por su sigla en inglés) subyacentes a las recomendaciones y la posología revisada de los medicamentos utilizados en los esquemas de segunda línea, así como las referencias clave. En línea se puede encontrar más información sobre los procesos del grupo de elaboración de las directrices y los participantes en dicho grupo, los principales métodos utilizados para desarrollar las recomendaciones, los resúmenes de la evidencia de la clasificación de la valoración, elaboración y evaluación de las recomendaciones (GRADE por su sigla en inglés) resultante y los marcos de decisión para cada recomendación, así como datos inéditos, planes de análisis de datos e informes de revisiones sistemáticas. Las recomendaciones y demás información práctica para apoyar su implementación se reproducirán en una próxima actualización del manual de la OMS sobre el manejo programático de la TB. Versión oficial en español de la obra original en inglés: WHO consolidated guidelines on drug-resistant tuberculosis treatment. © World Health Organization 2019. ISBN: 978-92-4-155052-9.

scholarly journals Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences

2019 ◽  
Vol 28 (153) ◽  
pp. 180115
Author(s):  
Edine Tiemersma ◽  
Susan van den Hof ◽  
Gunta Dravniece ◽  
Fraser Wares ◽  
Yohannes Molla ◽  
...  
Keyword(s):  
Drug Safety ◽  
Safety Monitoring ◽  
New Drugs ◽  
World Health ◽  
Middle Income ◽  
Beneficial Effects ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Drug Safety Monitoring ◽  
Health Organization

New drugs and shorter treatments for drug-resistant tuberculosis (DR-TB) have become available in recent years and active pharmacovigilance (PV) is recommended by the World Health Organization (WHO) at least during the early phases of implementation, with active drug safety monitoring and management (aDSM) proposed for this. We conducted a literature review of papers reporting on aDSM. Up to 18 April, 2019, results have only been published from one national aDSM programme. Because aDSM is being introduced in many low- and middle-income countries, we also report experiences in introducing it into DR-TB treatment programmes, targeting the reporting of a restricted set of adverse events (AEs) as per WHO-recommended aDSM principles for the period 2014–2017. Early beneficial effects of active PV for TB patients include increased awareness about the occurrence, detection and management of AEs during TB treatment, and the increase of spontaneous reporting in some countries. However, because PV capacity is low in most countries and collaboration between national TB programmes and national PV centres remains weak, parallel and coordinated co-development of the capacities of both TB programmes and PV centres is needed.

scholarly journals Drug-Resistant Tuberculosis 2020: Where We Stand

2020 ◽  
Vol 10 (6) ◽  
pp. 2153 ◽  
Author(s):  
Angelo Iacobino ◽  
Lanfranco Fattorini ◽  
Federico Giannoni
Keyword(s):  
Molecular Mechanisms ◽  
Drug Distribution ◽  
Multidrug Resistant ◽  
Diagnostic Methods ◽  
World Health ◽  
Drug Resistant ◽  
Comprehensive Overview ◽  
Resistant Tuberculosis ◽  
Health Organization ◽  
Incident Cases

The control of tuberculosis (TB) is hampered by the emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains, defined as resistant to at least isoniazid and rifampin, the two bactericidal drugs essential for the treatment of the disease. Due to the worldwide estimate of almost half a million incident cases of MDR/rifampin-resistant TB, it is important to continuously update the knowledge on the mechanisms involved in the development of this phenomenon. Clinical, biological and microbiological reasons account for the generation of resistance, including: (i) nonadherence of patients to their therapy, and/or errors of physicians in therapy management, (ii) complexity and poor vascularization of granulomatous lesions, which obstruct drug distribution to some sites, resulting in resistance development, (iii) intrinsic drug resistance of tubercle bacilli, (iv) formation of non-replicating, drug-tolerant bacilli inside the granulomas, (v) development of mutations in Mtb genes, which are the most important molecular mechanisms of resistance. This review provides a comprehensive overview of these issues, and releases up-dated information on the therapeutic strategies recently endorsed and recommended by the World Health Organization to facilitate the clinical and microbiological management of drug-resistant TB at the global level, with attention also to the most recent diagnostic methods.

scholarly journals Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

2019 ◽  
Vol 28 (152) ◽  
pp. 190035 ◽  
Author(s):  
Emanuele Pontali ◽  
Mario C. Raviglione ◽  
Giovanni Battista Migliori
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
Optimal Outcomes ◽  
Resistant Tuberculosis ◽  
Prolonged Duration ◽  
Mdr Tb ◽  
Revised Definitions ◽  
Health Organization

Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20–24 months), toxicity, costs and sub-optimal outcomes.After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9–10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.

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