白俄罗斯 HIV 阳性肺结核患者的肺结核药物敏感性、治疗和结果:来自国家和国际实验室的结果。

Tuberculosis Research and Treatment Pub Date : 2021-04-02 eCollection Date: 2021-01-01 DOI:10.1155/2021/6646239
Daria N Podlekareva, Dorte Bek Folkvardsen, Alena Skrahina, Anna Vassilenko, Aliaksandr Skrahin, Henadz Hurevich, Dzmitry Klimuk, Igor Karpov, Jens D Lundgren, Ole Kirk, Troels Lillebaek
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引用次数: 0

摘要

背景:为治愈耐药结核病(DR),抗结核治疗应在结核分枝杆菌药敏试验(DST)的指导下进行。在这项研究中,我们比较了在结核病 DR 高负担国家白俄罗斯明斯克进行的传统 DST 与在丹麦哥本哈根世界卫生组织结核病超国家参考实验室对结核病/艾滋病毒合并感染患者进行的广泛基因和表型分析。随后,将 DST 结果与治疗方案和疗效联系起来:方法:纳入明斯克的 30 名结核病/艾滋病毒合并感染患者,并进行描述性统计:根据明斯克的结果,10 名(33%)肺结核/艾滋病毒患者患有药物敏感性肺结核。2人(7%)患有单耐药异烟肼结核病,8人(27%)患有耐多药(MDR)结核病,5人(17%)患有广泛耐药(preXDR)结核病,5人(17%)患有广泛耐药(XDR)结核病。就一线药物利福平和异烟肼而言,明斯克和哥本哈根有 90% 的患者的 DST 检测结果一致。在二线抗结核药物方面,差异更为明显。有 14 名(47%)患者的至少一种药物存在差异,有 4 名(13%)患者在明斯克被归类为 MDR-TB 患者,但根据哥本哈根的 DST 结果却被归类为前 XDR-TB 患者。最初,所有患者都接受了利福平、异烟肼、吡嗪酰胺和乙胺丁醇的标准抗结核治疗。然而,根据 DST 结果,只有 40% 的患者适合接受这种治疗。DR-TB 患者平均在 1.5 个月(IQR 1-2)后更换为 4 种(IQR 3-5)活性药物。治疗调整后,治疗时间为 8 个月(IQR 2-11)。4名 DR-TB 患者(22%)的治疗时间超过 18 个月。在 24 个月的随访期间,共有 16 名(53%)患者死亡:我们发现明斯克实验室和哥本哈根实验室在利福平和异烟肼的 DST 检测上具有很高的一致性,而二线药物的差异则更为明显。对于 DR-TB 患者,治疗往往不够充分,相关调整也被延误。来自白俄罗斯明斯克的这个例子强调了 DR-TB 管理中的两个关键点:迫切需要在所有 DR-TB 高负担地区实施快速分子 DST 和提供二线药物。根据 DST 模式精心设计的个性化治疗方案可能会改善患者的治疗效果,并减少耐药结核分枝杆菌菌株的传播。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory.

Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory.

Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory.

Background: To cure drug-resistant (DR) tuberculosis (TB), the antituberculous treatment should be guided by Mycobacterium tuberculosis drug-susceptibility testing (DST). In this study, we compared conventional DST performed in Minsk, Belarus, a TB DR high-burden country, with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, for TB/HIV coinfected patients. Subsequently, DST results were related to treatment regimen and outcome.

Methods: Thirty TB/HIV coinfected patients from Minsk were included and descriptive statistics applied.

Results: Based on results from Minsk, 10 (33%) TB/HIV patients had drug-sensitive TB. Two (7%) had isoniazid monoresistant TB, 8 (27%) had multidrug-resistant (MDR) TB, 5 (17%) preextensive drug-resistant (preXDR) TB, and 5 (17%) had extensive drug-resistant (XDR) TB. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For the second-line anti-TB drugs, discrepancies were more pronounced. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. Initially, all patients received standard anti-TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. However, this was only suitable for 40% of the patients based on DST. On average, DR-TB patients were changed to 4 (IQR 3-5) active drugs after 1.5 months (IQR 1-2). After treatment adjustment, the treatment duration was 8 months (IQR 2-11). Four (22%) patients with DR-TB received treatment for >18 months. In total, sixteen (53%) patients died during 24 months of follow-up.

Conclusions: We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed. This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Carefully designed individualized treatment regimens in accordance with DST patterns will likely improve patients' outcome and reduce transmission with drug-resistant Mycobacterium tuberculosis strains.

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