Mycobacterium tuberculosis - atpE gene profile of bedaquiline-treated pulmonary tuberculosis patients at the referral hospital Dr. Soetomo, Indonesia.

Background: The atpE gene is a target for bedaquiline (Bdq)-activating drug action and mutations in the gene are fixed to cause resistance. However, changes in the amino acid of ATPase have been little reported from a clinical setting since it was first used in 2015 in Indonesia. This study aims to observe the sequence of nucleotide and amino acid from rifampicin-resistant (RR) pulmonary tuberculosis (TB) patients, both new and relapse cases treated with Bdq. Methods: This is an observational descriptive study performed in the referral hospital Dr Soetomo, Indonesia, at August 2022-November 2022. We performed Sanger sequencing and comparison of the atpE gene from the patient's sputum from August to November 2022 to wild-type Mycobacterium tuberculosis H37Rv and species of mycobacteria using BioEdit version 7.2 and BLAST NCBI software. We also conducted an epidemiological study on patients' characteristics. This study uses a descriptive statistic to show the percentage of data. Results: The total of 12 M. tuberculosis isolates showed that the atpE gene sequence was 100% similar to the wild-type M. tuberculosis H37Rv. No single-nucleotide polymorphisms or mutations were found, and no change in the amino acid structure at position 28 (Asp), 61 (Glu), 63 (Ala), and 66 (Ile). The percentage identity of atpE to M. tuberculosis H37Rv and M. tuberculosis complex was 99%-100%, while the similarity with the other mycobacteria species other than TB (Mycobacterium avium complex, Mycobacterium abscessus, and Mycobacterium lepraemurium) was 88%-91%. Conclusions: This study revealed M. tuberculosis -atpE gene sequence profile of RR-TB patients had no mutations, as the specific gene region, and no change in the amino acid structure. Therefore, Bdq can be continually trusted as an effective anti-tubercular drug in RR-TB patients.

The Profile of Multidrug Tuberculosis Regimen and Treatment Outcomes in Pulmonary MDR-TB Patients at the Tertiary Referral Hospital Dr. Soetomo, East Java, Indonesia: A Seven-Year Retrospective Study on Bedaquiline.

BACKGROUND: The use of bedaquiline has been reported to minimize the number of lost to follow-up and fewer rejections from the patients. This study is the first to depict the use of bedaquiline. It aims to provide information related to the profile of the MDR-TB drug regimen in the last 7 years with the treatment outcomes of pulmonary MDR-TB patients at a tertiary referral hospital in East Java. METHODS: This study was a retrospective, descriptive, and data analysis on 1053 pulmonary MDR-TB patients in tertiary referral hospital Dr Soetomo, East Java, Indonesia, with the SPSS software version 25 and Microsoft Excel 2021. RESULTS: The study analyzed the  MDR-TB treatment regimen following the latest guidelines from WHO (2020) at a tertiary referral hospital in East Java. This study shows that a bedaquiline-containing regimen started in January 2015 to July 2022 with the percentage of distribution (1, 3, 11, 4, 18, 13, 29, 21)% consecutively in the regimen. The treatment outcome profile of MDR-TB patients shows the average percentage of cured (15%), died (12%), lost-to-follow-up cases (27%), moved to an individualized regimen or a different health facility (42%), and currently in the evaluation stage (4%). Overall from January 2017 to July  2022, the number of LTFU cases decreased (42, 46, 29, 19, 8, 4)%. However, the cured case fluctuated between 2017-2022 (16, 28, 26, 32)%  respectively after Bdq started to be included in the regimen regularly for treating RR/MDR-TB. CONCLUSION: After seven years of study, we revealed an association between adding bedaquiline to the regimen and the treatment success and decreasing lost-to-follow-up cases.