Clinical Impact on Tuberculosis Treatment Outcomes of Discordance Between Molecular and Growth-Based Assays for Rifampin Resistance, California 2003-2013.
Clinical Impact on Tuberculosis Treatment Outcomes of Discordance Between Molecular and Growth-Based Assays for Rifampin Resistance, California 2003-2013.
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DOI：
10.1093/ofid/ofw150
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发表时间：
2016-09
影响因子：
4.2
通讯作者：
Desmond E
中科院分区：
文献类型：
--
作者：
Shah NS;Grace Lin SY;Barry PM;Cheng YN;Schecter G;Desmond E
背景：来自国际环境的数据表明，对利福平（RIF）敏感的rpoB突变结核分枝杆菌分离株可能具有临床意义。 我们分析了加州分子表型RIF结果不一致的患者的治疗结果。方法：我们纳入了2003-2013年期间的结核病患者，其标本经RIF易感表型检测，但经焦磷酸测序确定存在rpoB突变。 人口统计学数据来自加州结核病登记处。表型药物敏感性测试，病史，治疗和结果从病历中提取。结果：在3330个被检测的分离株中，413个标本有rpoB突变（12.4%）。 其中，16例（3.9%）具有分子表型不一致的RIF结果。鉴定出7个突变：511 Pro、516 Phe、526 Asn、526 Ser（AGC和TCC）、526 Cys和533 Pro。14例（88%）对异烟肼（INH）耐药，其中6例同时对乙胺丁醇（EMB）和/或吡嗪酰胺（PZA）表型耐药。5例患者（25%），1例511 Pro和4例526 Asn复发或治疗失败。3例患者的初始治疗方案为RIF、PZA和EMB; 1例患者接受RIF、PZA、EMB和氟喹诺酮类药物（CINN）; 1例患者接受RIF、EMB、CINN和一些二线药物。接受扩展方案重新治疗后，3例（75%）患者完成治疗，1例患者在治疗完成前转移，1例患者继续治疗。其余11例患者获得成功结局，其中9例接受了CFDN和/或利福霉素治疗。结论：利福平的分子表型不一致是罕见的，大多数分离株对异烟肼有耐药性。 未接受扩展方案的患者结局较差。这些突变可能具有临床意义，应考虑扩大治疗方案。
Background. Data from international settings suggest that isolates of Mycobacterium tuberculosis with rpoB mutations testing phenotypically susceptible to rifampin (RIF) may have clinical significance. We analyzed treatment outcomes of California patients with discordant molecular-phenotypic RIF results. Methods. We included tuberculosis (TB) patients, during 2003–2013, whose specimens tested RIF susceptible phenotypically but had a rpoB mutation determined by pyrosequencing. Demographic data were abstracted from the California TB registry. Phenotypic drug-susceptibility testing, medical history, treatment, and outcomes were abstracted from medical records. Results. Of 3330 isolates tested, 413 specimens had a rpoB mutation (12.4%). Of these, 16 (3.9%) had molecular-phenotypic discordant RIF results. Seven mutations were identified: 511Pro, 516Phe, 526Asn, 526Ser (AGC and TCC), 526Cys, and 533Pro. Fourteen (88%) had isoniazid (INH) resistance, 6 of whom were also phenotypically resistant to ethambutol (EMB) and/or pyrazinamide (PZA). Five patients (25%), 1 with 511Pro and 4 with 526Asn, relapsed or failed treatment. The initial regimen for 3 patients was RIF, PZA, and EMB; 1 patient received RIF, PZA, EMB, and a fluoroquinolone (FQN); and 1 patient received RIF, EMB, FQN, and some second-line medications. Upon retreatment with an expanded regimen, 3 (75%) patients completed treatment, 1 patient moved before treatment completion, and 1 patient continues on treatment. The remaining 11 patients had a successful outcome with 9 having received a FQN and/or a rifamycin. Conclusions. Rifampin molecular-phenotypic discordance was rare, and most isolates had INH resistance. Patients who did not receive an expanded regimen had poor outcomes. These mutations may have clinical importance, and expanded treatment regimens should be considered.
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