Neumann Marit, Reimann Maja, Chesov Dumitru, Popa Cristina, Dragomir Antonela, Popescu Oana, Munteanu Roxana, Hölscher Alexandra, Honeyborne Isobella, Heyckendorf Jan, Lange Christoph, Hölscher Christoph, Kalsdorf Barbara
Division of Infection Immunology, Research Center Borstel, Parkallee 1-40, 23845 Borstel, Germany; German Center for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany.
German Center for Infection Research (DZIF), Partner site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany; Division of Clinical Infectious Diseases, Research Center Borstel, Parkallee 1-40, 23845 Borstel, Germany; Respiratory Medicine & International Health, University of Lübeck, Lübeck, Germany.
J Infect. 2025 Feb;90(2):106399. doi: 10.1016/j.jinf.2024.106399. Epub 2024 Dec 27.
Early detection of treatment failure is essential to improve the management of drug-resistant tuberculosis (DR-TB). We evaluated the molecular bacterial load assay (MBLA) in comparison to standard diagnostic tests for monitoring therapy of patients affected by drug-resistant TB.
The performance of MBLA in tracking treatment response in a prospective cohort of patients with pulmonary MDR/RR- and pre-XDR/XDR-TB was compared with mycobacterial culture, mycobacterial DNA detection using GeneXpert (Xpert) and microscopy detection of sputum acid-fast-bacilli.
Mycobacterium tuberculosis culture conversion was used as the read-out for treatment responses. The MBLA was most concordant during the early phase of treatment, detecting changes in bacterial load with similar accuracy to microscopy and outperforming Xpert. When considering all timepoints, concordance with MGIT results was 72.1% for MBLA, 57.4% for Xpert and 76.7% for microscopy. The AUC for culture conversion was higher for MBLA (0.88, CI 0.84-0.95) than for Xpert (0.78, CI 0.72-0.85) and microscopy (0.77, CI 0.71-0.83).
MBLA was superior in the early identification of successful culture conversion compared to microscopy and Xpert and could be a useful biomarker to evaluate novel entities in Phase IIA early-bactericidal-activity drug trials regardless of the degree of M. tuberculosis drug resistance.
早期发现治疗失败对于改善耐多药结核病（DR-TB）的管理至关重要。我们评估了分子细菌载量测定法（MBLA）与标准诊断测试相比，在监测耐多药结核病患者治疗方面的效果。
将MBLA在一组前瞻性肺多药耐药/广泛耐药和预广泛耐药/广泛耐药结核病患者中追踪治疗反应的性能，与分枝杆菌培养、使用GeneXpert（Xpert）进行的分枝杆菌DNA检测以及痰涂片抗酸杆菌显微镜检测进行比较。
结核分枝杆菌培养转阴被用作治疗反应的读出指标。MBLA在治疗早期最为一致，检测细菌载量变化的准确性与显微镜检查相似，且优于Xpert。考虑所有时间点时，MBLA与MGIT结果的一致性为72.1%，Xpert为57.4%，显微镜检查为76.7%。MBLA培养转阴的AUC（0.88，CI 0.84 - 0.95）高于Xpert（0.78，CI 0.72 - 0.85）和显微镜检查（0.77，CI 0.71 - 0.83）。
与显微镜检查和Xpert相比，MBLA在早期识别成功的培养转阴方面更具优势，并且可能是评估IIA期早期杀菌活性药物试验中新型药物的有用生物标志物，无论结核分枝杆菌的耐药程度如何。
