Federal State Budgetary Institution "National Medical Research Center of Phthisiopulmonology and Infectious Diseases" of the Ministry of Health of the Russian Federation, Moscow.
World Health Organization, Regional Office for Europe, Copenhagen.
Monaldi Arch Chest Dis. 2021 Jan 14;91(1). doi: 10.4081/monaldi.2021.1678.
Treatment outcomes for Multidrug/Rifampicin-Resistant Tuberculosis (MDR/RR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) remain poor across the globe and in the Russian Federation. Treatment of XDR-TB is challenging for programmes and patients often resulting in low success rates and onward transmission of drug-resistant strains. Analysis of factors affecting culture conversion rate among XDR-TB patients may serve as a basis for optimization of treatment regimens. We conducted a retrospective cohort study using health records from 54 patients with pulmonary XDR-TB treated at a tertiary level facility in the Russian Federation. The study population included adult patients with culture-positive pulmonary XDR-TB who started treatment between 1 January 2018-30 June 2019. Culture conversion was defined as two consecutive negative cultures, collected at least 30 days apart. The date of sputum culture conversion was taken from the first of two consecutive negative sputum cultures fulfilling these criteria. We measured time to culture conversion using cumulative incidence functions accounting for competing risks and applied binary cause-specific Cox regressions to assess associated factors. Sputum culture conversion was recorded for 43 (79.6%) patients. Median time to culture conversion adjusted for competing risk of loss to follow up was 4 months [95% confidence interval (CI): 2-5]. The number of patients who had culture converted by treatment months 2, 4, and 6 were 12 (22%), 29 (54%) and 38 (70%) respectively. In unadjusted analysis, positive baseline sputum smear microscopy [hazard ratio (HR): 0.34, 95% CI: 0.18-0.66; p=0.001), hepatitis C (HR: 0.35, 95% CI: 0.14-0.89; p=0.023], and human immunodeficiency virus (HR: 0.30 95%, CI: 0.09-0.97; p=0.045), and receipt of fewer than 4 effective drugs in the treatment regimen (HR: 0.13, 95% CI: 0.03-0.60; p=0.009) were associated with delayed culture conversion. When compared to their combined use, patients receiving regimens with bedaquiline only (HR: 0.12, 95% CI: 0.03-0.49; p=0.003) or linezolid only (HR: 0.21, 95% CI: 0.06-0.69; p=0.010) were less likely to achieve timely culture conversion. Factors delaying sputum culture conversion should be considered in the management of patients with XDR-TB and considered by clinicians for regimen design and treatment strategies. Our study outlines the importance of simultaneous inclusion of bedaquiline and linezolid in treatment regimens for patients with XDR-TB to reduce time to sputum conversion and increase treatment success.
全球范围内，包括俄罗斯联邦在内，耐多药/利福平耐药结核病（MDR/RR-TB）和广泛耐药结核病（XDR-TB）的治疗效果仍然不佳。XDR-TB 的治疗对方案和患者来说极具挑战，往往导致成功率低，并导致耐药菌株的进一步传播。分析影响 XDR-TB 患者培养转换率的因素，可以为优化治疗方案提供依据。我们使用俄罗斯联邦一家三级医疗机构的 54 例肺 XDR-TB 患者的健康记录进行了回顾性队列研究。研究人群包括接受治疗的培养阳性肺 XDR-TB 成年患者，治疗开始于 2018 年 1 月 1 日至 2019 年 6 月 30 日。培养转换定义为至少相隔 30 天连续两次阴性培养。痰培养转换日期取自首次符合上述标准的连续两次阴性痰培养的第一天。我们使用考虑竞争风险的累积发病率函数来测量培养转换时间，并应用二元因果特定 Cox 回归来评估相关因素。43 例（79.6%）患者记录了痰培养转换。经竞争风险校正后，培养转换的中位时间为 4 个月[95%置信区间（CI）：2-5]。在治疗第 2、4 和 6 个月时，培养转换的患者人数分别为 12 例（22%）、29 例（54%）和 38 例（70%）。在未调整分析中，基线阳性痰涂片显微镜检查[风险比（HR）：0.34，95%CI：0.18-0.66；p=0.001]、丙型肝炎（HR：0.35，95%CI：0.14-0.89；p=0.023）和人类免疫缺陷病毒（HR：0.30，95%CI：0.09-0.97；p=0.045）以及治疗方案中接受的有效药物少于 4 种（HR：0.13，95%CI：0.03-0.60；p=0.009）与培养转换延迟有关。与联合使用相比，仅使用贝达喹啉（HR：0.12，95%CI：0.03-0.49；p=0.003）或仅使用利奈唑胺（HR：0.21，95%CI：0.06-0.69；p=0.010）的患者更不可能及时实现培养转换。在管理 XDR-TB 患者时应考虑延迟痰培养转换的因素，并由临床医生考虑用于方案设计和治疗策略。我们的研究强调了在 XDR-TB 患者的治疗中同时包含贝达喹啉和利奈唑胺的重要性，以减少痰培养转换时间并提高治疗成功率。
