Defining drug resistance beyond rifampicin: use of Xpert® MTB/XDR assay in tuberculous meningitis

Abstract

Purpose: - The emerging drug resistance in Tuberculous meningitis (TBM) worsens the prognosis and hamper elimination efforts. The need of the hour is a relatively simple, rapid, near point-of-care test that could allow universal drug susceptibility testing, beyond rifampicin (RIF). The current study evaluated performance of Xpert MTB/XDR in defining drug resistant TBM.

Methods: - A total of 45 cerebrospinal fluid samples (29 culture-positive, 16 culture-negative) reported TBM by Xpert MTB/Ultra were subjected to Xpert MTB/XDR to determine susceptibility towards isoniazid (INH), fluoroquinolones (FLQ), second-line injectables (SLID) and ethambutol (ETM). The performance of Xpert MTB/XDR was evaluated against genotypic drug susceptibility testing (line probe assay (LPA) and phenotypic drug susceptibility testing (culture)).

Results: - There was 100 % concordance between Xpert MTB/XDR and drug susceptibility using both culture and LPA for INH and SLIDs. For FLQ, the sensitivity and specificity of Xpert MTB/XDR was 93 % and 100 %, respectively against both culture and LPA, as there was one case each reported false-susceptible by Xpert MTB/XDR. The sensitivity and specificity of Xpert MTB/XDR for ETM was 93 % and 100 %, respectively against culture and one case of false-resistance was reported.

Conclusion: - Xpert MTB/XDR can serve as a useful tool to rapidly identify resistance to INH, FLQ, SLID and ETM, thus offering targeted therapy to the patients of TBM.

Keywords: Drug-resistant tuberculosis; Fluoroquinolone resistance; Isoniazid resistance; Molecular diagnosis; Tuberculous meningitis diagnosis.