LiquidArray MTB-XDR VER1.0检测结核分枝杆菌复合群、氟喹诺酮、阿米卡星、乙胺丁醇和利奈唑胺敏感性的诊断准确性。
Diagnostic accuracy of LiquidArray MTB-XDR VER1.0 for the detection of Mycobacterium tuberculosis complex, fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility.
作者信息
Auma Erick, Alberts Rencia, Derendinger Brigitta, Venter Rouxjeane, Streicher Elizabeth M, Pillay Samantha, Ghebrekristos Yonas T, Mburu Moses, Ruhwald Morten, Warren Robin, Penn-Nicholson Adam, Theron Grant, de Vos Margaretha
机构信息
DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
National Health Laboratory Service, Greenpoint Tuberculosis Laboratory, Cape Town, South Africa.
出版信息
Clin Infect Dis. 2024 Dec 12. doi: 10.1093/cid/ciae614.
BACKGROUND
Drug susceptibility testing (DST) is essential for starting people on effective tuberculosis (TB) regimens. No published data exists for the high-throughput LiquidArray MTB-XDR (LA-XDR) test, which detects Mycobacterium tuberculosis complex (MTBC) and fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility (latter two have no rapid DSTs available).
METHODS
We enrolled people (n=720) with presumptive TB who provided two sputa for a Xpert MTB/RIF Ultra and a culture (MTBC reference standard). Phenotypic DST and Sanger sequencing were the composite reference standards. LA-XDR on the manual FluoroLyse and automated GenoXtract-fleXT (fleXT) DNA extraction methods were compared.
RESULTS
For MTBC, LA-XDR had similar sensitivities (85-87%) and specificities (99%) using each extraction method. Drug susceptibility sensitivities varied: 94% (95% CI: 86, 98) for fluoroquinolones, 64% (45, 80) for amikacin, and 88% (79, 93) for ethambutol (specificities 97-100%). 6/7 (86%) resistant linezolid isolates were detected. LA-XDR with fleXT had indeterminate proportions of 21/251 (8%), 2/251 (1%), 63/251 (25%), and 93/251 (37%) for fluoroquinolones, ethambutol, amikacin, and linezolid, respectively (amikacin and linezolid indeterminates higher with Fluorolyse-extracted DNA). In a hypothetical population of 100 smear-negative people with fluoroquinolone-resistant TB undergoing fleXT DNA extraction, 24/100 (24%) would be missed (one extraction error, two invalid results, 15 MTBC-negative, six fluoroquinolone-indeterminate, one false-susceptible).
CONCLUSION
LA-XDR met the minimum WHO target product profile for a next-generation sputum-based moderate complexity DST with high fluoroquinolones and ethambutol resistance sensitivity, moderate amikacin resistance sensitivity, and promise for linezolid resistance, for which more data are needed. Improved LA-XDR MTBC detection would reduce missed resistance.
背景
药物敏感性检测（DST）对于启动患者有效的结核病（TB）治疗方案至关重要。目前尚无关于高通量液体阵列MTB-XDR（LA-XDR）检测的已发表数据，该检测可检测结核分枝杆菌复合群（MTBC）以及氟喹诺酮、阿米卡星、乙胺丁醇和利奈唑胺的敏感性（后两者尚无快速DST检测方法）。
方法
我们纳入了720名疑似结核病患者，他们提供两份痰液样本用于Xpert MTB/RIF Ultra检测和培养（MTBC参考标准）。表型DST和桑格测序为复合参考标准。比较了手动FluoroLyse和自动GenoXtract-fleXT（fleXT）DNA提取方法的LA-XDR检测结果。
结果
对于MTBC，使用每种提取方法的LA-XDR检测具有相似的敏感性（85-87%）和特异性（99%）。药物敏感性有所不同：氟喹诺酮类为94%（95%CI：86，98），阿米卡星为64%（45，80），乙胺丁醇为88%（79，93）（特异性为97-100%）。检测到6/7（86%）的利奈唑胺耐药菌株。采用fleXT提取DNA的LA-XDR检测中，氟喹诺酮、乙胺丁醇、阿米卡星和利奈唑胺的不确定比例分别为21/251（8%）、2/251（1%）、63/251（25%）和93/251（37%）（采用Fluorolyse提取的DNA检测阿米卡星和利奈唑胺时不确定比例更高）。在一个假设的100名涂片阴性且对氟喹诺酮耐药的结核病患者群体中，若采用fleXT提取DNA，24/100（24%）的患者结果会出现遗漏（1例提取错误、2例无效结果、15例MTBC阴性、6例氟喹诺酮检测结果不确定、1例假敏感）。
结论
LA-XDR检测符合世界卫生组织下一代基于痰液的中等复杂度DST的最低目标产品要求，对氟喹诺酮和乙胺丁醇耐药的敏感性高，对阿米卡星耐药的敏感性中等，对利奈唑胺耐药检测有前景，但还需要更多数据。改进LA-XDR对MTBC的检测将减少耐药漏检情况。
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