000			02962 am a22002893u 4500
042			_adc
100	1	0	_aPillay, S _eauthor _92949
700	1	0	_ade Vos, M _eauthor _92950
700	1	0	_aDerendinger, B _eauthor _92951
700	1	0	_aStreicher, E _eauthor _92952
700	1	0	_aDolby, T _eauthor _92953
700	1	0	_aScott, LA _eauthor _92954
700	1	0	_aSteinhobel, AD _eauthor _92955
700	1	0	_aWarren, RM _eauthor _92956
700	1	0	_aTheron, G _eauthor _92957
245	0	0	_aNon-actionable results, accuracy and effect of the first- and second-line line probe assays for diagnosing drug resistant tuberculosis, including on smear-negative specimens, in a high-volume laboratory
260			_c2022-07-05.
500			_a/pmc/articles/PMC7614164/
500			_a/pubmed/35788278
520			_aBACKGROUND: Rapid drug susceptibility testing (DST) is crucial to confirm eligibility for new tuberculosis (TB) regimens. Genotype MTBDRsl is a widely-deployed World Health Organization (WHO)-endorsed assay yet programmatic performance data, including non-actionable results from smear-negative sputum, are scarce. METHODS: Sputa from Xpert MTB/RIF-rifampicin resistant individuals (n=951) were tested by Genotype MTBDRplus and MTBDRsl (both v2) in a routine laboratory. Phenotypic DST was the second-line drug reference standard. Discrepant results underwent Sanger sequencing. FINDINGS: 89% (849/951) individuals were culture-positive [56% (476/849) smear-negative]. MTBDRplus had at least one non-actionable result (control and/or TB-detection bands absent or invalid, precluding resistance reporting) in 19% (92/476) of smear-negatives and, for MTBDRsl, 40% (171/427) were non-actionable [28% (120/427) false-negative TB, 17% (51/427) indeterminate]. In smear-negatives, MTBDRsl sensitivity for fluoroquinolones was 84% (95% CI 67-93), 81% (54-95) for second-line injectables, and 57% (28-82) for both. Specificities were 93% (89-98), 88% (81-93), and 97% (91-99), respectively. 23% (172/746) of Xpert rifampicin-resistant specimens were MTBDRplus isoniazid-susceptible. Days-to-second-line-susceptibility reporting with the programmatic advent of MTBDRsl improved [6 (5-7) vs. 37 (35-46); p<0.001]. CONCLUSION: MTBDRsl did not generate a result in almost half of smear-negative individuals (4/10 failed), resulting in substantial missed resistance. However, if MTBDRsl generates an actionable result, that result is accurate in ruling-in second-line resistance. Isoniazid susceptibility testing remains crucial. This study provides, in the context of WHO guidance, real-world direct second-line susceptibility testing performance data on non-actionable results (which, if unaccounted for, result in an overestimation of test utility), accuracy, and care cascade impact.
540			_a
546			_aen
690			_aArticle
655	7		_aText _2local
786	0		_nClin Infect Dis
856	4	1	_uhttp://dx.doi.org/10.1093/cid/ciac556 _zConnect to this object online.
999			_c486 _d486