Stoltz A, Nathavitharana R R, de Kock E, Ueckermann V, Jensen P, Mendel C M, Spigelman M, Nardell E A
Department of Infectious Diseases, University of Pretoria School of Medicine, Pretoria, South Africa.
Division of Infectious Diseases, Beth Israel Deaconess Hospital, Boston, Massachusetts, USA.
J Infect Dis. 2025 Jul 30;232(1):143-151. doi: 10.1093/infdis/jiaf005.
Most drug-resistant tuberculosis occurs due to transmission of unsuspected or ineffectively treated drug-resistant tuberculosis. The duration of treatment to stop person-to-person spread of drug-resistant tuberculosis is uncertain. We evaluated the impact of novel regimens, including BPaL (bedaquiline, 1200-mg linezolid, and pretomanid), on drug-resistant tuberculosis transmission, using the human-guinea pig (H-GP) transmission model.
In experiment 1, patients initiated an optimized drug-resistant tuberculosis regimen including bedaquiline and linezolid. In experiment 2, patients initiated the BPaL regimen. We measured baseline infectivity for each cohort by exhausting ward air to one of two guinea pig exposure rooms (control group), each containing 90 guinea pigs, for 8 patient-days. Then, after 72 hours of treatment, ward air was exhausted to the second guinea pig exposure room for 8 patient-days (intervention group). The infectiousness of each cohort was compared by performing tuberculin skin tests in guinea pigs at baseline (before treatment) and 6 weeks after the exposure period.
In experiment 1, before treatment, 5 patients with drug-resistant tuberculosis infected 24 of 90 guinea pigs (26.7%) (control group). After treatment (72 hours after drug initiation), the same patients infected 25 of 90 guinea pigs (27.8%) (intervention group) (P > .99). In experiment 2, before treatment, 9 patients with drug-resistant tuberculosis infected 40 of 90 guinea pigs (44.4%) (control group). After treatment (beginning 72 hours after drug initiation), the same patients infected 0 of 90 guinea pigs (0%) (intervention group) (P < .0001).
In this study, drug-resistant tuberculosis drug regimens, including bedaquiline and standard-dose linezolid for 72 hours, did not decrease drug-resistant tuberculosis transmission. In contrast, transmission was rapidly and completely inhibited in patients treated with BPaL for 72 hours, suggesting an early and profound impact on transmission.
大多数耐药结核病是由于未被察觉或治疗无效的耐药结核病传播所致。阻止耐药结核病在人与人之间传播的治疗持续时间尚不确定。我们使用人-豚鼠（H-GP）传播模型评估了包括BPaL（贝达喹啉、1200毫克利奈唑胺和普瑞玛尼）在内的新型方案对耐药结核病传播的影响。
在实验1中，患者开始使用包括贝达喹啉和利奈唑胺的优化耐药结核病方案。在实验2中，患者开始使用BPaL方案。我们通过将病房空气排放到两个豚鼠暴露室之一（对照组）来测量每个队列的基线传染性，每个暴露室包含90只豚鼠，持续8个患者日。然后，在治疗72小时后，将病房空气排放到第二个豚鼠暴露室，持续8个患者日（干预组）。通过在基线（治疗前）和暴露期后6周对豚鼠进行结核菌素皮肤试验，比较每个队列的传染性。
在实验1中，治疗前，5例耐药结核病患者感染了90只豚鼠中的24只（26.7%）（对照组）。治疗后（开始用药72小时后），同样的患者感染了90只豚鼠中的25只（27.8%）（干预组）（P>.99）。在实验2中，治疗前，9例耐药结核病患者感染了90只豚鼠中的40只（44.4%）（对照组）。治疗后（开始用药72小时后），同样的患者感染了90只豚鼠中的0只（0%）（干预组）（P<.0001）。
在本研究中，包括贝达喹啉和标准剂量利奈唑胺治疗72小时的耐药结核病药物方案并未降低耐药结核病的传播。相比之下，接受BPaL治疗72小时的患者的传播迅速且完全受到抑制，这表明对传播有早期且深远的影响。
