Effectiveness and safety of the Bedaquiline-containing six-month chemotherapy regimens in pulmonary tube rculosis patients

Background. The second-line drugs optionally combined with the WHO’s “fifth group” drugs (especially linezolid) are effective in MDR-TB patients. In some cases, the adequate chemotherapy (min 4 drugs) is unrealizable due to the extended drug-resistance (XDR) and/or treatment intolerance. The new drug – bedaquiline (Bdq) – is essential, but it is not yet thoroughly tested in regimens with traditional TB-drugs and new anti-mycobacterial agents.
Design and Methods. The prospective unblinded non-randomized onecentered study include 54 pulmonary TB patients, 18-73 years old, 68,5% male and 31,5% female, 20,4% (20 pts) new and 79,8% (31 pts) retreated. MDR was identified in 37,0% (20 pts) and XDR – in 57,4% (31 pts). Lung cavities were detected in 87,0% (47 pts), bilateral lesions – in 61,1% (33 pts). Bdq was included in regimens in all patients, the next some wеre, if possible (based on mycobacterial drug-resistance patterns and patients drug tolerances), linezolid (96,3% – 52 pts), cycloserine / terizidone (81,5% – 44 pts), fluoroquinolones (70,4% – 38 pts), capreomycin (46,8% – 25 pts), prothionamide (29,6% – 16 pts), PAS (27,8% – 15 pts), pyrazinamide (18,7% – 10 pts), ethambutol (13,0% – 7 pts). If the regimen didn’t include at least four drugs, we add macrolides (38,9% – 21 pts), meropenum (9,5% – 5 pts), amoxicillin / clavulanic acid (1 pt), isoniazid in high doses (2 pt). The evaluation was performed after 24 weeks of Bdq administration.
Results. The treatment with Bdq was completed in 87,0% (47 pts), in 4 pts (7,4%) treatment was interrupted (but they weren’t lost to follow-up) and in 3 pts (5,6%) Bdq was excluded due to the serious adverse events. The evident involution of symptoms were obtained in 85,1% (35/43 pts), the X-ray improvement – in 85,1% (40/47 pts). The sputum smear conversion totally score (on liquid media): 87,2% (30/36 pts) with Med = 4 wks (IQR 2,0-11,5). The time of conversion and conversion rate were similar in MDR- and XDRTB, but significantly (р < 0,05) depend on large cavities. 12 incidents of SAE III-IV were obtained in 11 pts (20,4%): toxic hepatitis (3), hypereosinophilia (19% and more – 3), QTс prolongation up to 520 ms (2, without arrhythmia), obstinate vomiting (2), hyperkalemia and azotemia (1) and anemia (Hb < 69 g/l) – in 1 pt. The bedaquilin administration was stopped in 3 pts (5,6 %) and interrupted in 3.
Conclusion. The regimens, based on Bdq, second-line TB-drugs and the “fifth group” drugs are well-tolerated and high effective in MDR- and XDRTB. We need to obtain data to argue the prolongation of Bdq course for 9–12 months’.

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