Department of Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
South African Medical Research Council Centre for Tuberculosis Research/DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Stellenbosch, South Africa.
J Antimicrob Chemother. 2020 May 1;75(5):1123-1129. doi: 10.1093/jac/dkz564.
Molecular assays are endorsed for detection and confirmation of rifampicin-resistant TB. The frequency, causal mechanisms and impact of discordant results between molecular tests are not well understood.
The prevalence of discordant results was determined by pairwise comparison of molecular test results in a cohort of 749 rifampicin-resistant TB patients in three South African provinces. Culture isolates were sent to a research laboratory for WGS and rifampicin MIC determination. Clinical information was collected through medical file review.
The prevalence of discordances between Xpert MTB/RIF and MTBDRplus was 14.5% (95% CI 10.9%-18.9%), 5.6% (95% CI 2.2%-13.4%) between two consecutive Xpert assays and 4.2% (95% CI 2.2%-7.8%) between two consecutive MTBDRplus assays. Likely mechanisms of discordances were false rifampicin susceptibility on MTBDRplus (due to variants not included in mutant probes or heteroresistance with loss of minor variants in culture), false resistance on molecular assay in rifampicin-susceptible isolates, and human error. The healthcare worker changed the treatment regimen in 33% of patients with discordant results and requested 232 additional molecular tests after a first confirmatory test was performed in 460 patients. A follow-up Xpert assay would give the healthcare worker the 'true' rifampicin-resistant TB diagnosis in at least 73% of discordant cases.
The high rate of discordant results between Xpert and MTBDRplus has important implications for the laboratory, clinician and patient. While root causes for discordant result are multiple, a follow-up Xpert assay could guide healthcare workers to the correct treatment in most patients.
分子检测被推荐用于检测和确认利福平耐药结核。但目前对于分子检测结果不一致的频率、因果机制及其影响尚不清楚。
对南非三个省份的 749 例利福平耐药结核患者的队列进行分子检测结果的两两比较，确定不一致结果的发生率。培养物分离株被送到一个研究实验室进行 WGS 和利福平 MIC 测定。通过病历回顾收集临床信息。
Xpert MTB/RIF 和 MTBDRplus 之间的不一致率为 14.5%（95%CI 10.9%-18.9%），两次连续 Xpert 检测之间的不一致率为 5.6%（95%CI 2.2%-13.4%），两次连续 MTBDRplus 检测之间的不一致率为 4.2%（95%CI 2.2%-7.8%）。不一致的可能机制是 MTBDRplus 上的假利福平敏感性（由于突变探针未包含的变体或培养物中少数变体的异质性丢失导致的假耐药）、利福平敏感培养物中分子检测的假耐药以及人为错误。在 33%的不一致结果患者中，医护人员改变了治疗方案，在对 460 例患者中的首次确认性检测后，又要求进行了 232 次额外的分子检测。在至少 73%的不一致病例中，后续的 Xpert 检测可使医护人员做出“真正的”利福平耐药结核诊断。
Xpert 和 MTBDRplus 之间的高不一致率对实验室、临床医生和患者都有重要影响。虽然不一致结果的根本原因是多方面的，但后续的 Xpert 检测可以指导大多数患者的医护人员做出正确的治疗决策。
