Huo Fengmin, Ma Yifeng, Liu Rongmei, Ma Liping, Li Shanshan, Jiang Guanglu, Wang Fen, Shang Yuanyuan, Dong Lingling, Pang Yu
National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.
Open Forum Infect Dis. 2020 Jul 5;7(8):ofaa279. doi: 10.1093/ofid/ofaa279. eCollection 2020 Aug.
The 3-month difference in turnaround time between Xpert and conventional phenotypic drug susceptibility testing (pDST) causes patient treatment challenges when pDST rifampin (RIF) susceptibility results and earlier Xpert results disagree, resulting in unnecessary tuberculosis (TB) patient exposure to toxic second-line drugs. Here, the prevalence of discordant RIF susceptibility test results, specifically Xpert (resistant) vs pDST (susceptible) results, was determined.
Tuberculosis patients enrolled between January 2015 and June 2018 at Beijing Chest Hospital who consecutively tested positive for RIF resistance using Xpert then negative using pDST were studied. DNA sequences and minimal inhibitory concentration (MIC) results provided insights for understanding discordant results.
Of 26826 patients with suggestive TB symptoms undergoing Xpert MTB/RIF testing, 728 diagnosed as RIF-resistant were evaluated. Of these, 118 (16.2%) exhibiting Xpert RIF resistance and phenotypic RIF susceptibility yielded 104 successfully subcultured isolates; of these, 86 (82.7%) harbored gene RIF resistance-determining region mutations and 18 (17.3%) did not. The Leu511Pro (25.0%) and Leu533Pro (17.3%) mutations were most frequently associated with discordant RIF susceptibility test results. Of the 86 isolates with mutations, 42 (48.8%) with MICs ≤1.0 mg/L were assigned to the RIF-susceptible group, with Leu511Pro being the most common mutation observed. Isolates with a very low bacterial load were most frequently misdiagnosed as RIF-resistant by Xpert.
Approximately one-sixth of RIF-resistant TB isolates identified via Xpert yielded discordant pDST results due to questionable interpretation of specific "disputed" mutations. Thus, a diagnostic flowchart should be used to correctly interpret Xpert RIF resistance results to best guide patient treatment.
当Xpert检测结果与传统表型药物敏感性试验（pDST）利福平（RIF）敏感性结果不一致时，Xpert与传统pDST在周转时间上3个月的差异给患者治疗带来了挑战，导致结核病（TB）患者不必要地暴露于有毒的二线药物。在此，确定了RIF敏感性试验结果不一致的发生率，特别是Xpert（耐药）与pDST（敏感）结果不一致的情况。
对2015年1月至2018年6月在北京胸科医院登记的结核病患者进行研究，这些患者使用Xpert连续检测RIF耐药呈阳性，然后使用pDST检测呈阴性。DNA序列和最低抑菌浓度（MIC）结果为理解不一致的结果提供了线索。
在26826例有疑似TB症状并接受Xpert MTB/RIF检测的患者中，对728例诊断为RIF耐药的患者进行了评估。其中，118例（16.2%）表现为Xpert RIF耐药但表型RIF敏感，获得了104株成功传代培养的分离株；其中，86株（82.7%）携带rpoB基因RIF耐药决定区突变，18株（17.3%）未携带。Leu511Pro（25.0%）和Leu533Pro（17.3%）突变与RIF敏感性试验结果不一致最为相关。在86株有rpoB突变的分离株中，42株（48.8%）MIC≤1.0mg/L被归为RIF敏感组，Leu511Pro是最常见的突变。细菌载量极低的分离株最常被Xpert误诊为RIF耐药。
通过Xpert鉴定的RIF耐药TB分离株中，约六分之一因对特定“有争议”突变的可疑解读而产生不一致的pDST结果。因此，应使用诊断流程图正确解读Xpert RIF耐药结果，以最佳指导患者治疗。
