False-positive Xpert<SUP>®</SUP> MTB/RIF more than seven years after cure

Effect of previous treatment and sputum quality on diagnostic accuracy of Xpert® MTB/RIF

“…17 Previously treated TB patients are key to current WHO treatment algorithms because the prevalence of antituberculosis drug resistance is 5-10 times higher than in 'new' TB patients. Our findings are consistent with the initial case reports [6][7][8] and two recent studies from Lower Xpert specificity in previously treated TB Zimbabwe and South Africa, where Xpert specificity was respectively 87% and 92%. [7][8][9] These results collectively stand in contrast with the initial validation and implementation trials where Xpert achieved an overall specificity of 99%.…”

“…Our findings are consistent with the initial case reports [6][7][8] and two recent studies from Lower Xpert specificity in previously treated TB Zimbabwe and South Africa, where Xpert specificity was respectively 87% and 92%. [7][8][9] These results collectively stand in contrast with the initial validation and implementation trials where Xpert achieved an overall specificity of 99%. 1,4,5 We suspect that post-enrollment exclusions of AFB-positive, culturenegative patients and the inclusion of lower proportions of retreatment cases could have led to an overestimation of the specificity of Xpert in the initial trials.…”

“…5 However, recent studies in programmatic conditions have suggested lower specificities of Xpert in previously treated patients (~90%). [6][7][8][9] Patients with discordant cultureÀ, Xpertþ results are currently thought to have 'false-positive' Xpert results as a result of remnant, non-viable bacilli after anti-tuberculosis treatment. 8,9 However, despite its known impact on the yield of other diagnostic methods such as AFB smear microscopy and culture, [10][11][12] limited attention has been placed on the effect of sputum quality on Xpert diagnostic performance.…”

Discordant results of Xpert MTB/Rif assay and BACTEC MGIT 960 liquid culture to detect Mycobacterium tuberculosis in community screening in Vietnam

“…Another driver of Xpert(+)MGIT(−) discordance was a history of previous TB treatment. This is in line with findings from other studies that non-viable bacterial DNA can persist in sputum samples of treated TB patients for up to 7 years after cure [ 26 – 28 ]. In these cases, it is uncertain to conclude that the Xpert results were false positive or these individuals were experiencing recurrent TB disease with low bacterial load, so they were referred to local district TB units for further diagnosis and treatment.…”

Xpert MTB/RIF Results in Patients With Previous Tuberculosis: Can We Distinguish True From False Positive Results?

“…Xpert is used routinely in patients who have previously had tuberculosis [6,7]. This is despite evidence that approximately 30% of patients who are microbiologically cured after 6 months of treatment are Xpert positive [8], a proven correlation between retreatment status and diminished specificity [9][10][11], and several case reports detailing false-positive (FP) Xpert results in retreatment cases [12][13][14]. Detectable mycobacterial DNA, which can be extracellular or associated with nonintact cells (and hence is not culturable), is a possible cause of this false positivity, which may trigger unwarranted treatment and unnecessarily expose patients to toxic drugs, delay establishing the correct underlying diagnosis and its appropriate treatment, and escalate healthcare costs.…”