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A groundbreaking study published in Lancet Infectious Diseases has revealed that quabodepistat, in combination with delamanid and bedaquiline, could provide a safer and faster treatment option for pulmonary tuberculosis (TB). The research investigates the safety and bactericidal efficacy of quabodepistat, which showed promising results in both laboratory and clinical tuberculosis strains.
In 2022, tuberculosis was responsible for an alarming 1.3 million deaths worldwide. The standard treatment for TB typically targets the inhibition of Bacilli replication, elimination of dormant bacilli, and prevention of drug resistance. While long-duration regimens have been the cornerstone of treatment for drug-resistant tuberculosis, many patients have struggled to tolerate these prolonged courses, which can result in incomplete treatments.
Combination therapies, particularly those involving diarylquinoline (bedaquiline), nitroimidazoles, and pretomanid, have been recommended for multidrug-resistant tuberculosis. The recent study highlights quabodepistat as a potent addition to these regimens, with the ability to enhance bactericidal effects and potentially improve patient outcomes.
Quabodepistat, a 3,4-dihydrocarbostyril derivative, has demonstrated strong bactericidal activity, especially with low minimum inhibitory concentrations, meaning it can effectively target TB bacteria while requiring lower drug concentrations. When tested on healthy adults, the drug showed favorable tolerance at doses ranging from 10 mg to 480 mg.
In a pilot study, quabodepistat was combined with delamanid and bedaquiline, with pharmacokinetics and bactericidal activity evaluated at days one and fourteen of the trial. The efficacy of the treatment was assessed by measuring the reduction in sputum colony-forming units (CFUs) from baseline to day 14, along with the concentration of sputum lipoarabinomannan using enzyme-linked immunosorbent assay (ELISA). Additionally, mycobacterial growth was tracked using the mycobacterial growth indicator tube (MGIT) time-to-detection method.
Approximately 73% of patients in the trial experienced at least one treatment-emergent adverse event, most of which were mild or moderate. A small percentage (5%) of patients in the quabodepistat + bedaquiline group experienced severe adverse events, but these were not directly linked to the drug combination. Notably, moderate hyperkalemia was observed in the bedaquiline cohort, attributed to pre-existing conditions at baseline.
Overall, the study indicated strong bacteriological effects and safety for the combination of quabodepistat, delamanid, and bedaquiline, offering hope for safer and faster TB treatments. However, the researchers emphasize that these promising results need to be validated through large-scale, long-term clinical trials before the therapy can be considered a standard treatment option.
Disclaimer: This article is based on a recent study published in Lancet Infectious Diseases and is for informational purposes only. The findings discussed here are preliminary and require further confirmation through additional research. Always consult healthcare professionals for medical advice regarding tuberculosis treatment.
(Source: News-Medical.net)
