Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents428 culture-confirmed MDR-TB cases were analysed (615% male; 221% HIV-positive, 456% XDR-TB) MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (820%, 584%, 526% and 153% of cases, respectively)Sputum smear and culture conversion rates in MDR-TB cases were 636% and 301%, respectively at 30 days, 811% and 567%, respectively at 60 days; 855% and 805%, respectively at 90 days and 887% and 912%, respectively at the end of treatment The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days Out of 247 culture-confirmed MDR-TB cases completing treatment, 713% achieved success (624% cured; 89% completed treatment), 134% died, 73% defaulted and 77% failed Bedaquiline was interrupted due to adverse events in 58% of cases A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline relatedBedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions

https://erj.ersjournals.com/content/erj/49/5/1700387.full.pdf

Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study

https://pure.bond.edu.au/ws/files/35844852/2020_MDR_XDR_TB_management_of_patients_and_contacts.pdf

MDR/XDR-TB management of patients and contacts: challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.

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.

https://erj.ersjournals.com/content/erj/54/6/1901522.full-text.pdf

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

Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin (RIF) and isoniazid (INH) resistance and Mycobacterium tuberculosis detection. Genotype MTBDRplusV1 was WHO-endorsed in 2008 but newer LPAs have since been developed.

This systematic review evaluated three LPAs: Hain Genotype MTBDRplusV1, MTBDRplusV2 and Nipro NTM+MDRTB. Study quality was assessed with QUADAS-2. Bivariate random-effects meta-analyses were performed for direct and indirect testing. Results for RIF and INH resistance were compared to phenotypic and composite (incorporating sequencing) reference standards. M. tuberculosis detection results were compared to culture.

74 unique studies were included. For RIF resistance (21 225 samples), pooled sensitivity and specificity (with 95% confidence intervals) were 96.7% (95.6–97.5%) and 98.8% (98.2–99.2%). For INH resistance (20 954 samples), pooled sensitivity and specificity were 90.2% (88.2–91.9%) and 99.2% (98.7–99.5%). Results were similar for direct and indirect testing and across LPAs. Using a composite reference standard, specificity increased marginally. For M. tuberculosis detection (3451 samples), pooled sensitivity was 94% (89.4–99.4%) for smear-positive specimens and 44% (20.2–71.7%) for smear-negative specimens.

In patients with pulmonary TB, LPAs have high sensitivity and specificity for RIF resistance and high specificity and good sensitivity for INH resistance. This meta-analysis provides evidence for policy and practice.

https://erj.ersjournals.com/content/erj/49/1/1601075.full.pdf

Accuracy of line probe assays for the diagnosis of pulmonary and multidrug-resistant tuberculosis: a systematic review and meta-analysis

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.

https://err.ersjournals.com/content/errev/28/152/190035.full.pdf

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

The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment To our knowledge, no review has ever evaluated this topic in a comprehensive manner Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements") The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search Manuscripts written in English, Spanish, and Russian were selected The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosisThe evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae RESUMO O papel da tuberculose como uma prioridade de saude publica e a disponibilidade de ferramentas diagnosticas para avaliar o estado funcional (espirometria, pletismografia e DLCO), a gasometria arterial, a capacidade de realizar exercicios, as lesoes (radiografia de torax e TC) e a qualidade de vida justificam o esforco de se considerar o que deve ser feito quando os pacientes completam seu tratamento Ate onde sabemos, nenhuma revisao avaliou esse topico de forma abrangente Nosso objetivo foi revisar as evidencias disponiveis e obter algumas conclusoes sobre o futuro papel da fase de "tratamento pos-tuberculose", que ira potencialmente impactar milhoes de casos todos os anos Realizou-se uma revisao nao sistematica da literatura tendo como base uma pesquisa no PubMed usando palavras-chave especificas (varias combinacoes dos termos "tuberculose", "reabilitacao", "tuberculose multirresistente", "doenca pulmonar", "doenca pulmonar obstrutiva", e "medidas de volume pulmonar") As listas de referencias dos artigos principais foram recuperadas para melhorar a sensibilidade da busca Foram selecionados manuscritos escritos em ingles, espanhol e russo As principais areas de interesse foram sequelas de tuberculose apos diagnostico e tratamento; "pulmao destruido"; avaliacao funcional das sequelas; intervencoes de reabilitacao pulmonar (fisioterapia, oxigenoterapia de longo prazo e ventilacao); e tuberculose multirresistente As evidencias encontradas sugerem que a tuberculose e definitivamente responsavel por sequelas funcionais, principalmente causando um padrao obstrutivo na espirometria (mas tambem padroes restritivos e mistos) e que ha razao para a reabilitacao pulmonar Fornecemos tambem uma lista de variaveis a serem discutidas em futuros estudos sobre reabilitacao pulmonar em pacientes com sequelas pos-tuberculose

/pdf/is-there-a-rationale-for-pulmonary-rehabilitation-following-zbqcnjot8z.pdf

Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis

Applicability of the shorter 'Bangladesh regimen' in high multidrug-resistant tuberculosis settings.

Joint ALAT/ERS/PAHO strategic alliance develops roadmap for TB elimination in Latin American and Caribbean countries http://ow.ly/RbHH3034gY6

https://erj.ersjournals.com/content/erj/48/5/1282.full.pdf

Zhenia Fuentes

Papers

Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis

Applicability of the shorter 'Bangladesh regimen' in high multidrug-resistant tuberculosis settings.

Roadmap for tuberculosis elimination in Latin American and Caribbean countries: a strategic alliance.