Individualized Regimen of Bedaquilin-Delamanid to The Modulation of Level of

IP-10, MMP-9, Resistance and Safety Profile in Patients with Drug-Resistant

Tuberculosis

 Oki Nugraha Putra

 

 

Background: Bedaquilin and delamanid have been included in the individualized treatment regimen (ITR) to treat patients with drug-resistant tuberculosis (DR-TB). Objectives: The aims of this study were to analyze sputum culture conversion, level of IP-10 and MMP-9, QTc interval prolongation, and resistance profile of regimens containing bedaquilin and delamanid in DR-TB patients. Methods: It was a prospective cohort of DR-TB patients who received regimens containing bedaquilin and delamanid between September 2022 and May 2023. The study was conducted at the outpatient department of MDR-TB of the Dr. Soetomo Hospital. Patients were divided into two groups, bedaquilin and bedaquilin-delamanid group, respectively. Sputum culture and QTc interval were evaluated at baseline and monthly until sixth month. IP-10 and MMP-9 levels were evaluated at baseline and bimonthly until sixth month. Mutation of atpE and ddn was evaluated at baseline and during treatment. Results: Sixty-three DR-TB patients met the inclusion criteria, 51 in the bedaquilin and 12 in bedaquilin-delamanid group. After six months of treatment, 81.8% and 100% patients had sputum culture conversion and time to culture conversion was 2.75 months and 1.42 months in bedaquilin and bedaquilin-delamanid group, P-value 0.045 and 0.047,

respectively. IP-10 and MMP-9 levels were significantly lower after six months between the two groups. Grade II and III of QTc interval prolongation was higher in bedaquilin-delamanid group, P-value 0.084. However, mean difference of QTc interval was < 60 ms during six months of treatment between the two groups, P-value ≥ 0.05. No mutation was observed in atpE gene and two from eight isolates (25.0%) were detected mutation for ddn gene. Conclusion: DR-TB patients who received all oral ITR containing bedaquilin and or delamanid demonstrated favorable sputum conversion with a tolerable safety profile.

 

Keywords: DR-TB; Bedaquilin; Delamanid; Effectiveness; Safety