Discordances between molecular assays for rifampicin resistance in Mycobacterium tuberculosis: frequency, mechanisms and clinical impact
Discordances between molecular assays for rifampicin resistance in Mycobacterium tuberculosis: frequency, mechanisms and clinical impact
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DOI：
10.1093/jac/dkz564
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发表时间：
2020-05-01
影响因子：
5.2
通讯作者：
Warren, Robin M.
中科院分区：
文献类型：
--
作者：
Van Rie, Annelies;Whitfield, Michael G.;Warren, Robin M.
背景：分子分析被认可用于检测和确认利福平耐药结核病。分子检测结果不一致的频率、因果机制和影响尚未得到很好的理解。方法：通过对南非三个省749例利福平耐药结核病患者分子检测结果的两两比较，确定不一致结果的发生率。培养分离物送研究实验室进行WGS和利福平MIC测定。通过查阅病历收集临床资料。结果：Xpert MTB/RIF与MTBDRplus之间不一致的发生率为14.5% (95% CI 10.9%-18.9%)，连续两次Xpert检测之间不一致的发生率为5.6% (95% CI 2.2%-13.4%)，连续两次MTBDRplus检测之间不一致的发生率为4.2% （95% CI 2.2%-7.8%）。不一致的可能机制是MTBDRplus对利福平的假敏感性（由于突变探针中未包括的变异或培养中丢失的小变异的异源抗性），利福平敏感分离株的分子测定中的假抗性，以及人为错误。在结果不一致的33%患者中，卫生保健工作者改变了治疗方案，并在对460名患者进行首次确证性检测后要求进行232次额外的分子检测。在至少73%的不一致病例中，后续的专家化验将给卫生保健工作者“真正的”利福平耐药结核病诊断。结论：Xpert与MTBDRplus检测结果的高不一致性对实验室、临床和患者具有重要意义。虽然导致不一致结果的根本原因是多方面的，但后续的Xpert分析可以指导医护人员对大多数患者进行正确的治疗。
Background: 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.Methods: 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.Results: 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.Conclusions: 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.