Xpert MTB/RIF Ultra检测脑脊液对结核性脑膜炎的诊断价值

Diagnostic Accuracy of Xpert MTB/RIF Ultra for Tuberculous Meningitis

目的评估超敏结核分枝杆菌和利福平耐药基因(Xpert MTB/RIF Ultra,简称“Xpert Ultra”)检测脑脊液(cerebral spinal fluid,CSF)对结核性脑膜炎(tuberculous meninges,TBM)的诊断价值。方法连续纳入2017年1月至2018年12月首都医科大学附属北京胸科医院就诊的疑似TBM患者189例,依据入组标准最终纳入151例,其中临床诊断TBM患者106例(包括32例确诊、55例很可能,19例可能),非TBM患者45例。收集所有患者的CSF,评价抗酸染色涂片镜检、BACTEC MGIT960培养(简称“MGIT960培养”)、GeneXpert MTB/RIF(简称“Xpert”)和Xpert Ultra检测CSF对TBM的诊断效能。结果以临床诊断为参考标准,Xpert Ultra对106例临床诊断TBM患者检测的敏感度[(44.3%,47/106)]明显高于Xpert[24.5%(26/106)],差异有统计学意义(x^(2)=16.000,P<0.01);对76例行CSF培养的TBM患者的检测敏感度[44.7%(34/76)]明显高于MGIT 960培养[18.4%(14/76)],差异有统计学意义(x^(2)=12.893,P<0.01)。纳入Xpert Ultra检测结果后,诊断TBM的确诊率从30.2%(32/106)上升至50.0%(53/106)。Xpert Ultra对62例培养阴性患者的阳性检出率[38.7%(24/62)]明显高于Xpert[21.0%(13/62)],差异有统计学意义(x^(2)=7.692,P=0.003)。Xpert和Xpert Ultra对接受抗结核治疗TBM患者CSF的阳性检出率[分别为13.3%(8/60)和20.0%(12/60)]均明显低于未接受抗结核治疗患者[分别为39.1%(18/46)和76.1%(35/46)],差异均有统计学意义(x^(2)=9.360,P=0.002;33.189,P<0.01);且Xpert Ultra对未接受抗结核治疗的TBM患者的阳性检出率明显高于Xpert(x^(2)=15.059,P<0.01)。Xpert Ultra和Xpert同时检出利福平耐药者1例,利福平敏感者5例,与表型药物敏感性试验结果一致。结论Xpert Ultra检测CSF诊断TBM的敏感度明显高于Xpert和MGIT 960培养:且在培养阴性的TBM患者中,Xpert Ultra阳性检出率明显优于Xpert。Xpert Ultra可快速诊断TBM,值得临床推广应用。

Objective To evaluate the performance of Xpert MTB/RIF Ulltra(Xpert Ultra)for tuberculous meningitis(TBM)diagnosis.Methods All of 189 TBM suspected patients were consecutively enrolled from January 2017 to December 2018 at Bejing Chest Hospital.According to the clinical reference standard,the final sample size for analysis was 151 patients,which included 32 definite TBM,55 probable TBM,19 possible TBM,and 45 non-TBM patients.Uncentrifuged CSF specimens collected from each patient were subjected to smear,culture,Xpert and Xpert Ultra.The sensitivity and specificity of all the tests were assessed against uniform clinical case definitions of TBM.Results The direct head-to-head diagnostic performance comparison showed higher sensitivity of Xpert Ultra in contrast with Xpert(44.3%(47/106)vs.24.5%(26/106);x^(2)=16.000,P<0.01)among 106 TBM patients.Xpert Ultra also produced a higher sensitivity than culture(44.7%,(34/76)vs.18.4%(14/76);x^(2)=12.893,P<0.01)in 76 having culture results patients.When Xpert Ultra outcomes were integrated,the percentage of definite TBM cases increased from 30.2%(32/106)to 50.0%(53/106).Besides,among 62 patients with CSF culture-negative,the positive rate of Xpert Ultra was also higher than Xpert(38.7%(24/62)vs.21.0%(13/62);x^(2)=7.692,P=0.003).Both Xpert Ultra(76.1%(35/46)v5.20.0%(12/60);33.189,P<0.01)and Xpert(39.1%(18/46)vs.13.3%(8/60);x^(2)=9.360,P=0.002)produced higher positive rate in patients without prior anti-TB treatment than those under anti-TB therapy.The positive rate of Xpert Ultra was higher than Xpert in patients without prior anti-TB treatment(x^(2)=15.059,P<0.01).Both Xpert Ultra and Xpert acurately identified the one rifampicin(RFP)-resistant and the 5 RFP-sensitive cases defined by phenotypic drug sensitivity test.Conclusion Xpert Ultra outperformed both Xpert and culture for TBM diagnosis,especially for CSF culture negative TBM patients*making it a useful tool for rapid diagnosis of TBM.