Can the GeneXpert MTB/XDR deliver on the promise of expanded, near-patient tuberculosis drug-susceptibility testing?

Abstract

Early diagnosis, including universal drug-susceptibility testing for all patients with tuberculosis, remains a key priority for tuberculosis elimination by 2035. The drug-resistant tuberculosis care cascade remains persistently challenged by substantial gaps in timely diagnosis and treatment of drug-resistant tuberculosis. Current diagnostics for drug-resistant tuberculosis are limited with respect to accuracy, time to results, affordability, suitability for resource-poor endemic settings, and accessibility for use at the point of care. WHO endorsement of the novel Xpert MTB/XDR assay holds notable promise for expanding access to testing and rapid diagnosis of tuberculosis drug resistance. The Xpert MTB/XDR assay detects resistance to isoniazid, ethionamide, fluoroquinolones, and second-line injectables, and is indicated for testing in patients with confirmed pulmonary tuberculosis. However, this iteration of the Xpert MTB/XDR cartridge might have less of an effect than expected, as WHO has since downgraded the role of second-line injectable agents in treating drug-resistant tuberculosis, and has revised case definitions of drug-resistant tuberculosis to incorporate resistance to new drugs. This Personal View explores the strengths and limitations of the Xpert MTB/XDR assay in the detection of drug resistance, the assay's ability to inform appropriate drug-resistant tuberculosis drug selection, and the optimal placement of the Xpert XDR assay in the laboratory diagnostic workflow.