Centner C M, Munir R, Tagliani E, Rieß F, Brown P, Hayes C, Dolby T, Zemanay W, Cirillo D M, David A, Schumacher S G, Denkinger C M, Ruhwald M, Leukes V N, Nicol M P, Van der Walt I, Kisten G, Gumede M, Mace A, Brink A, Stevens W, Scott L, Penn-Nicholson A, Cox H
Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa.
Open Forum Infect Dis. 2024 Jul 31;11(8):ofae437. doi: 10.1093/ofid/ofae437. eCollection 2024 Aug.
The World Health Organization-approved Xpert MTB/XDR test detects and resistance to isoniazid, fluoroquinolones, ethionamide, and injectable drugs directly in specimens. This pragmatic, laboratory-based study assessed the diagnostic accuracy and feasibility of a reflex testing approach, where Xpert MTB/XDR was performed on residual specimens previously processed for Xpert MTB/RIF Ultra.
Routine respiratory specimens, processed for Xpert MTB/RIF Ultra, were stored in sample reagent buffer at 2°C-8°C. If rifampicin resistant, the residual specimen was assessed for adequate volume (≥2 mL) and tested with Xpert MTB/XDR, with storage time recorded. A second specimen was used for routine and reference standard testing (culture and sequencing).
Specimens (99% sputum) from 763 participants submitted to 2 large routine laboratories were included. Xpert MTB/XDR yielded valid resistance detection results in 639 (84%), compared with 507 (66%) for routine testing (difference [95% CI], 18% [13%-22%]). The median turnaround time for results was 23 hours for Xpert MTB/XDR and 15 days for routine testing. While 748 specimens (98%) were ≥2 mL, only 102 (13%) were stored for ≤4 hours. By the reference standard, 284 of 394 (72%) were isoniazid resistant, and 57 of 380 (15%) were fluroquinolone resistant. The sensitivities of Xpert MTB/XDR were 94% (95% CI, 91%-97%) for isoniazid and 91% (81%-97%) for fluoroquinolone resistance detection. The specificities were 98% (94%-100%) and 100% (98%-100%), respectively.
Xpert MTB/XDR performed favorably compared with the reference, and the reflex testing approach increased results availability over routine testing, while dramatically decreasing turnaround time from weeks to hours. Laboratory workflow precluded testing within the manufacturer-recommended 4-hour storage time, but longer storage did not appear detrimental.
世界卫生组织批准的Xpert MTB/XDR检测可直接在标本中检测对异烟肼、氟喹诺酮类、乙硫异烟胺和注射用药物的耐药性。这项基于实验室的实用性研究评估了一种复检方法的诊断准确性和可行性，即对先前为Xpert MTB/RIF Ultra检测而处理过的剩余标本进行Xpert MTB/XDR检测。
为Xpert MTB/RIF Ultra检测而处理的常规呼吸道标本保存在2°C至8°C的样本试剂缓冲液中。如果对利福平耐药，则评估剩余标本的体积是否足够（≥2毫升），并用Xpert MTB/XDR进行检测，同时记录保存时间。另一份标本用于常规检测和参考标准检测（培养和测序）。
纳入了提交给2家大型常规实验室的763名参与者的标本（99%为痰液）。Xpert MTB/XDR在639例（84%）标本中得出了有效的耐药性检测结果，而常规检测为507例（66%）（差异[95%CI]，18%[13%-22%]）。Xpert MTB/XDR检测结果的中位周转时间为23小时，常规检测为15天。虽然748份标本（98%）体积≥2毫升，但只有102份（13%）保存时间≤4小时。根据参考标准，394例中有284例（72%）对异烟肼耐药，380例中有57例（15%）对氟喹诺酮耐药。Xpert MTB/XDR检测异烟肼耐药性和氟喹诺酮耐药性的敏感性分别为94%（95%CI，91%-97%）和91%（81%-97%）。特异性分别为98%（94%-100%）和100%（98%-100%）。
与参考标准相比，Xpert MTB/XDR表现良好，复检方法比常规检测增加了结果的可获得性，同时将周转时间从数周大幅缩短至数小时。实验室工作流程排除了在制造商推荐的4小时保存时间内进行检测的可能性，但更长时间的保存似乎并无不利影响。
