Utility of second sample testing in Indian children suffering from tuberculosis with rifampicin indeterminate results on Xpert MTB/Rif and Xpert Ultra assays.

BACKGROUND

Nucleic acid amplification tests (NAAT) for tuberculosis (TB) can rapidly detect Mycobacterium tuberculosis (MTB) and rifampicin resistance (RR). However, they may yield rifampicin indeterminate (RI)-results which pose a significant diagnostic and therapeutic challenge. Current guidelines suggest performing NAAT on a second sample and treating with first-line antitubercular therapy (ATT) until actionable results are obtained on NAAT or other drug-resistance assays. The aim of this study is to determine the detection yield, type of rifampicin sensitivity, and clinical implications of second sample testing on NAAT for TB (Xpert MTB/Rif or Ultra) in patients with RI-results on the first sample.

METHODS

A retrospective study was conducted including all pediatric TB patients with RI-results on their first sample NAAT. Data on specimen type, and second sample NAAT results was analyzed.

RESULTS

One-hundred and sixteen patients were included. Second sample testing was done in 95 (81.90 %) patients of which 67 (70.5 %) samples were pulmonary and 28 (29.5 %) samples were extrapulmonary. For pulmonary samples, 10 (14.93 %) detected MTB, of which 2 (20 %) were RI, 6 (60 %) were rifampicin sensitive (RS) and 2 (20 %) were RR. For extrapulmonary samples, 14 (50 %) detected MTB, of which only 1 (7.14 %) was RI, 8 (57.14 %) were RS, and 5 (35.71 %) were RR. On second sample testing, the rates of RR for lymph nodes and tissue samples was 33.33 % and 50 %, respectively.

CONCLUSION

Repeat pulmonary sample testing on NAAT in patients with RI-results on the first sample are less likely to detect MTB and are more likely to be rifampicin sensitive, thus, patients may be empirically treated with first-line ATT if a second sample cannot be collected. Repeat extrapulmonary sample testing on NAAT in patients with RI results on the first sample are likely to detect MTB, have actionable results on NAAT, and may have RR results. Thus, collecting a second extrapulmonary sample, particularly lymph nodes and tissues, should be done in those in whom it is feasible.