Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery
Introduction
With over 490,000 multidrug-resistant tuberculosis cases (MDR-TB; TB caused by Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin) occurring globally each year, 6.2% of which are XDR-TB (extensively drug-resistant TB: MDR-TB with additional resistance to fluoroquinolones and one second-line injectable), the ‘white plague’ remains a major clinical and public health priority.1, 2, 3, 4
Although higher success rates are achievable,1, 2 the overall proportion of treatment success is sub-optimal, adverse events common, and treatment duration long and expensive.1, 2, 3, 4 Currently, scientific debate focuses on the role of new medications (bedaquiline and delamanid),5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and repurposed drugs for the optimal management of difficult-to-treat M/XDR-TB cases.16, 17, 18, 19
Few studies are presently available on the programmatic use of bedaquiline1,4, 5, 6, 7 and no study has evaluated the contribution of adjunctive surgery in bedaquiline-treated patients.20, 21 The aim of this study is to describe treatment outcomes and complications in a cohort of drug-resistant pulmonary TB cases treated with bedaquiline-containing regimens having indication for surgical intervention (the vast majority of them have been operated).
Section snippets
Materials and methods
This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries from January 2007 to March 2015.
Patients who had surgical indications in a bedaquiline-treated programme-based cohort2 were selected and surgery-related information collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes (per World Health Organization (WHO)
Results
Fifty-seven cases of drug-resistant TB managed with both surgical indication and bedaquiline-containing regimens were included (52 from the original study plus 4 added from the Russian Federation and 1 from Italy) as follows: Russian Federation (39), South Africa (5), India (4), Italy (3) and Peru (2); Argentina, Australia, Greece, and Sweden contributed with one case.
Overall, 5 cases were new and 52 had been previously treated for M/XDR-TB (37 failures, 15 relapses).
The majority were male
Discussion
We describe for the first time the use of adjunctive surgery in severe M/XDR-TB cases treated with bedaquiline-containing regimen achieving satisfactory outcomes and high bacteriological conversion rates.
Although the treatment success in this sample (69.1%) was lower than in the larger cohort previously reported (77%),2 it is still 10% higher than that reported by WHO.1 In a large systematic review and meta-analysis of 1,572 MDR-TB cases undergoing surgery, long-term treatment success was
Acknowledgments
The paper is part of the ERS/ALAT and the ERS/SBPT collaborative projects (ERS: European Respiratory Society; ALAT: Latin-American Society of Respiratory Medicine; SBPT: Brazilian Society of Pulmonology) and of the operational research plan of the WHO Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, ITA-80, 2017-2020- GBM/RC/LDA. It is also under the umbrella of the Global TB Network hosted by WAidid (World Association for Infectious Diseases and Immunological Disorders).
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declarations of interest
None.
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Outcomes of patients undergoing lung resection for drug-resistant TB and the prognostic significance of pre-operative positron emission tomography/computed tomography (PET/CT) in predicting treatment failure
2023, eClinicalMedicineCitation Excerpt :However, bedaquiline and linezolid were not widely available at the time, and the degree of drug resistance, prevalence of pre-operative culture positivity, and degree of HIV positivity at the time of surgery were much higher in our study. Nevertheless, our outcomes are better than those of historical cohorts of XDR patients treated with conventional chemotherapy alone,31 but worse than those of recent cohorts treated with bedaquiline and linezolid, with or without surgery.8,15,32 This could be explained by the above-mentioned microbiological and patient-specific factors including disease extent, HIV status, and likely later presentation in our setting with poor access to cardiothoracic services.
Risk factors for early mortality in patients with pulmonary tuberculosis admitted to the emergency room
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Predicting treatment failure risk in a Chinese Drug-Resistant Tuberculosis with surgical therapy: Development and assessment of a new predictive nomogram
2020, International Journal of Infectious DiseasesCitation Excerpt :WHO recently issued guidelines that the drug-resistant tuberculosis patient could be operated upon after two months of anti-tuberculosis therapy before surgery (World Health Organization, 2019); Chinese scholars put forward an “operation time window” of three months for the reinforcement stage. In general, sufficient effective anti-tuberculosis treatment before surgery could inhibit the number of tuberculosis bacteria and their activity (Borisov et al., 2019). We defined “T1” as a standard chemotherapy cycle for unfinished MDR/XDR-TB but more than two months before surgery; “T2” as more than one standard chemotherapy cycle for MDR/XDR-TB was completed before surgery; “T3” as A standard chemotherapy regimen for MDR/XDR-TB was given less than two months, or no standard chemotherapy regimen was given before surgery.
Early treatment outcome of bedaquiline plus optimised background regimen in drug resistant tuberculosis patients
2020, Indian Journal of Tuberculosis