Abstract:

Objective: To evaluate the efficacy and safety of a novel all-oral short-course regimen for the treatment of multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis (TB). Methods: A retrospective analysis was conducted on the clinical data of three MDR/RR-TB patients who received a short-course oral regimen containing new drugs (bedaquiline, contezolid and delamanid) at Beijing Chest Hospital in December 2023. Using the keywords “multidrug-resistant tuberculosis, contezolid” and “multidrug-resistant tuberculosis, bedaquiline, delamanid” relevant studies were retrieved from CNKI, Wanfang, and PubMed databases. A total of 11 studies were identified, 8 of which included new drugs such as contezolid, delamanid and bedaquiline. The efficacy and safety of these regimens were analyzed in combination with the clinical data of the three reported cases. Results: Efficacy analysis revealed that 84% of patients receiving contezolid-based regimens achieved negative sputum cultures and (or) smears for Mycobacterium tuberculosis. Chest CT scans indicated lesion improvement, with stability maintained after treatment cessation. Among patients treated with bedaquiline and delamanid-based regimens, 91% showed favorable outcomes. The sputum culture conversion rate for Mycobacterium tuberculosis was 95% at week 8 and remained at 95% at week 24 of treatment. Additionally, the median time to sputum culture conversion in the bedaquiline and delamanid group was shorter compared to that of the bedaquiline-only group. Safety analysis revealed that no cases of myelosuppression, peripheral neuropathy, or optic neuropathy were observed in patients receiving contezolid-based regimens. In the bedaquiline and delamanid group, the QTcF interval increased by an average of 20.7 ms from baseline (mean range: 16.1 ms to 25.3 ms), with 2 patients experiencing a QT prolongation of >500 ms. Additionally, 4 patients experienced 6 instances of QTcF prolongation exceeding baseline by 60 ms. No grade 3 or 4 QTc prolongation events, arrhythmias, permanent treatment discontinuations, or deaths were reported. The extent of QTc prolongation was lower in the bedaquiline and delamanid group compared to the bedaquiline-only group. During treatment, 52% of patients developed myelosuppression, and 42% experienced peripheral neuropathy. By 48 weeks of follow-up, most adverse events had resolved. Conclusion: The all-oral short-course regimen containing new drugs (bedaquiline, delamanid, and contezolid) demonstrated promising efficacy in patients with multidrug-resistant or rifampicin-resistant tuberculosis. No serious drug-related adverse events were observed throughout the treatment course.

Key words: Tuberculosis, multidrug-resistant, Auti-tuberculosis drugs, Combination drug therapy, Evaluation studies