Diagnostic accuracy of LiquidArray MTB-XDR VER1.0 for the detection of Mycobacterium tuberculosis complex, fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility.

Abstract

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.