Clinical perspectives on treatment of rifampicin-resistant/multidrug-resistant TB.

Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.

Bedaquiline and delamanid result in low rates of unfavourable outcomes among TB patients in Eswatini.

SETTING: Since 2015, Eswatini has been scaling up bedaquiline (BDQ) and delamanid (DLM) based drug-resistant TB treatment regimens under programmatic conditions.OBJECTIVE: Identification of factors associated with treatment outcomes in patients receiving BDQ and/or DLM either as a new treatment initiation or drug substitution.DESIGN: This is a retrospective cohort study of patients receiving BDQ and/or DLM in Eswatini between March 2015 and October 2018. We describe factors associated with unfavourable treatment outcomes (death, lost to follow-up, treatment failure and amplification of resistance) and culture conversion using multivariable flexible parametric survival and competing-risks regression analyses.RESULTS: Of 352 patients receiving BDQ and/or DLM, 7.8% and 21.2% had an unfavourable treatment outcome at 6 and 24 months, respectively. Predictors were age ≥ 60 years (adjusted hazard ratio aHR 4.49, 95%CI 1.61-12.57) vs. age 20-39 years, and a treatment regimen combining both drugs (aHR 4.49, 95%CI 1.61-12.57) vs. BDQ only. The probability of culture conversion was increased for two health facilities and patients with a poly resistance profile (adjusted sub-hazard ratio 2.01, 95%CI 1.13-3.59) vs. multidrug resistance.CONCLUSION: Single use of BDQ or DLM was associated with low rates of unfavourable outcomes, suggesting that these medications may be effectively adopted at scale under routine programmatic conditions. Combined use of BDQ and DLM was a risk factor for unfavourable outcomes and should prompt for collection of more data on the combined use of these medications.

Model of care and risk factors for poor outcomes in patients on multi-drug resistant tuberculosis treatment at two facilities in eSwatini (formerly Swaziland), 2011-2013.

INTRODUCTION: Since 2011 Médecins sans Frontières together with the eSwatini Ministry of Health have been managing patients with multi-drug resistant tuberculosis (MDR-TB) at Matsapha and Mankayane in Manzini region. This analysis describes the model of care and outcomes of patients receiving a 20 months MDR-TB treatment regimen between 2011 and 2013. METHOD: We conducted a retrospective observational cohort study of MDR-TB patients enrolled for treatment between May 2011 and December 2013. An extensive package of psychological care and socio-economic incentives were provided including psychological support, paid treatment supporters, transport fees and a monthly food package. Baseline demographic details and treatment outcomes were recorded and for HIV positive patient's univariate analysis as well as a cox regression hazard model were undertaken to assess risk factors for unfavorable outcomes. RESULTS: From the 174 patients enrolled, 156 (89.7%) were HIV co-infected, 102 (58.6%) were female, median age 33 years old (IQR: 28-42), 55 (31.6%) had a BMI less than 18 and 86 (49.4%) had not been previously treated for any form of TB. Overall cohort outcomes revealed a 75.3% treatment success rate, 21.3% mortality rate, 0.6% failure and 0.6% lost to follow-up rate. In the adjusted multivariate analysis, low BMI and low CD4 count at treatment initiation were associated with an increased risk of unfavorable outcome. CONCLUSIONS: A model of care that included psychosocial support and patient's enablers led to a high level of treatment success with a very low lost to follow up rate. Limiting the overall treatment success was a high mortality rate which was associated with advanced HIV and a low BMI at presentation. These factors will need to be addressed in order to improve upon the overall treatment success rate in future.

Operational aspects of bedaquiline implementation in Swaziland: report from the field.

Bedaquiline (BDQ) has been recommended by the World Health Organization for the treatment of multi-drug-resistant tuberculosis (MDR-TB) since 2013, but experience using the drug in high-burden, lower-income countries is limited and case studies are needed. Swaziland started using BDQ under national TB programme conditions in 2015 in four pilot sites. As of 1 December 2016, 93 patients had been initiated on BDQ, i.e., 19% of MDR-TB patients treated in the country. Swaziland has developed a systematic and efficient model for BDQ introduction in collaboration with several partners. This model is also being used to introduce other innovations and can serve as an example for other countries facing similar challenges.

La bédaquiline (BDQ) a été recommandée par l'Organisation Mondiale de la Santé pour le traitement de la tuberculose multirésistante (TB-MDR) depuis 2013, mais l'expérience de son utilisation dans des pays à faible revenu et durement touchés est limitée et des études de cas sont requises. Le Swaziland a commencé à utiliser la BDQ dans des conditions de programme national TB en 2015 dans quatre sites pilotes. Au 1er décembre 2016, 93 patients avaient été mis sous BDQ, c'est-à-dire 19% des patients TB-MDR traités dans le pays. Le Swaziland a élaboré un modèle systématique et efficace d'introduction de la BDQ en collaboration avec plusieurs partenaires. Ce modèle est également utilisé pour introduire d'autres innovations et peut servir d'exemple à d'autres pays confrontés à des défis similaires.

La Organización Mundial de la Salud recomienda desde el 2013 la bedaquilina (BDQ) en el tratamiento de la tuberculosis multirresistente (TB-MDR), pero la experiencia con su utilización en los países con alta carga de morbilidad es limitada y se precisan estudios de casos. En Swazilandia, se comenzó a utilizar la BDQ en el contexto del programa nacional contra la TB en cuatro centros piloto en el 2015. Al 1° de diciembre del 2016, 93 pacientes habían iniciado el tratamiento con BDQ, es decir, el 19% de los casos de TB-MDR tratados en el país. En Swazilandia se ha elaborado un modelo sistemático y eficiente de introducción de este medicamento en colaboración con diversos asociados. El modelo se utiliza también con el propósito de aplicar otras medidas innovadoras y puede servir como ejemplo a los países que afrontan dificultades semejantes.