Bedaquiline containing regimen showed excellent efficacy and safety for the treatment of pre-extensively drug-resistant tuberculosis

Abstract

Abstract Background Pre-extensively drug-resistant tuberculosis (Pre XDR-TB) was defined as resistant to fluroquinolones in Multidrug resistant tuberculosis (MDR TB), it had poorer outcomes than MDR TB in previous reports. In this study, we aimed to evaluate the efficacy and safety of the Bdq containing regimen for the treatment of Pre XDR-TB. Moreover, we tried to explore the optimal duration of Bdq and the total duration. Patients and methods : In this retrospective study, a total of 84 Pre XDR-TB from our hospital were enrolled and divided into Bdq group (46 cases) and non Bdq group (38 cases) according to their treatment regimen. Demographic, socioeconomic and clinical features were analyzed and compared between them in order to find out the factors associated with the outcomes. Then we compared the efficacy and safety between bedaquiline(Bdq) and non-bedaquiline containing regimens for treatment of Pre XDR-TB. Meanwhile, we analyze the outcomes among different Bdq duration and total regimen duration. P < 0.05 is significantly different, GraphPad prism 5.0 software package was used to process the data. Results 1.more male and younger cases as well as higher BMI appeared in Bdq group, In addition, medical care insurance types in Bdq group were superior comparing to those in non Bdq group( p < 0.05). More cases in Bdq group had taken Lzd for more than 1 month than non Bdq group before(p < 0.05). 2. The most frequent used drugs were Bdq(100%), Lzd(94%), Cs(82.61%), Cfz(73.91), etc in order for Bdq regimen. While the drugs were Lzd(94.74%), Cs(81.58%), Mfx(71.05%), Pza(71.05), Cfz(55.26%), etc in order for non Bdq regimen. 3. Favorable outcomes of Bdq group were significantly superior to non Bdq group( 89.13% vs 52.63%, p = 0.0002). While unfavorable outcomes of Bdq group was significantly lower than non Bdq group(10.87% vs 47.37%, p = 0.0002). 4. Both 2 patients who received Bdq for ≤ 12w(12w and 6w respectively) and a total duration < 9 months had unfavorable outcomes. While 2 of 4 patients (2/4, 50%) who receive Bdq for 18w-32w and a total duration < 9 months had also poor outcome. By contrast, all 22 cases who received Bdq for 18w-52w and a total duration 9–12 months had favorable outcomes. Another subgroup of 20 cases who received Bdq for 24w-52w and a total duration 13–24 month also got 100% favorable outcomes. In the longest duration subgroup ( Bdq for 36w total duration for 30–36 months), 1 in 3 patients obtained unfavorable outcome. 5. Safety assessment. The most common adverse effects are hyperuricemia, skin hyperpigmentation, QTc prolongation, peripheral neuritis, anemia etc in order. Most of the AEs are gentle and tolerant, SAEs which led to interruption of treatment or withdrawal of the suspected drug were rare, they mainly included severe Peripheral neuritis, Anemia, Liver injury, Anxiety or depression, etc. Conclusions Our study showed Bdq containing regimen achieved better outcomes for Pre XDR-TB compared with non Bdq (89.13% vs 52.63%, p < 0.01). AEs related to Bdq was mild, no case interrupted the treatment as a result of AEs associated with Bdq. Moreover, extension of Bdq duration was effective and tolerant. Generalization of Bdq is one of the vital measures to overcome this disease, but it needs to be managed standardly.