Tuberculosis impacts multiple aspects in quality of life in a Romanian cohort of drug‐susceptible and drug resistant patients: A patient‐reported outcome measures study

Background: Tuberculosis (TB), and especially its drug resistant forms, is responsible for not only significant mortality, but also considerable morbidity, still under‐quantified. This study used four Patient‐Reported Outcome Measures (PROMS) to assess the status of persons affected by drug‐susceptible and drug‐resistant TB during their TB treatment or after treatment completion, in Romania, the highest TB burden country in the EU. Methods: People affected by TB in two different regions in Romania were included during and after treatment, following a cross‐sectional design. PROMs used were SF‐36, EQ‐5D‐5L, WPAI and the app‐based audiometry screening tool ‘uHear.’ Descriptive statistics and relevant statistical tests were used to compare groups between themselves and with the general Romanian population. Results: Both patients with drug‐susceptible and drug‐resistant TB experience, with drug‐resistant patients experiencing statistically significantly more pain and hearing loss. PROMs show some improvement in the after‐treatment group; however, compared with the general Romanian population for which data were available, all groups scored lower on all outcome measures. Conclusion: PROMs offer the possibility of obtaining a more comprehensive view of patients' status, by involving them directly in the medical process and could guide a rehabilitation strategy

A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis

Background: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. Objective: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Methods: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. Results: A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 – 0.84). Conclusions: We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted