Suboptimal specificity of Xpert MTB/RIF among treatment-experienced patients.

The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is strongly recommended by the World Health Organization as an initial diagnostic test for treatment-experienced patients of any retreatment category [1–3]. Yet, retreatment tuberculosis (TB) suspects have been infrequently included in studies of Xpert [4], probably because current-generation PCR-based tests are unable to determine Mycobacterium tuberculosis viability [5]. Indeed, Xpert is known to frequently remain positive at the end of standard short-course therapy [6], with case reports emerging of Xpert false-positivity for up to 5 years post-treatment completion [7, 8]. Furthermore, 56% (n=3485/6285) of specificity data informing the most recent Cochrane meta-analysis [4] was derived from validation and demonstration studies [9, 10], which may be optimistic due to selection bias related to post-enrolment exclusions [7]. Not surprisingly, there have been increasing calls to clarify the guidelines for use of Xpert among treatment-experienced patients [11].