To Test or Not? Xpert MTB/RIF as an Alternative to Smear Microscopy to Guide Line Probe Assay Testing for...

Area of Science:

• Clinical microbiology and infectious diseases
• Diagnostic test optimization
• Tuberculosis drug resistance surveillance

Background:

• Xpert MTB/RIF has transformed tuberculosis (TB) diagnostics.
• Current guidelines often exclude smear-negative specimens from reflex drug susceptibility testing (DST).
• This exclusion risks missing critical resistance information.

Purpose of the Study:

• To evaluate the utility of Xpert MTB/RIF bacterial load data for predicting drug susceptibility assay results in smear-negative TB specimens.
• To determine optimal strategies for expanding direct DST to smear-negative samples.
• To analyze the trade-offs between actionable results and missed resistance.

Main Methods:

• Receiver operator characteristic (ROC) curve analysis was performed on Xpert MTB/RIF data (smear grade, semi-quantitation categories, Cтmin values).
• Data from sputum specimens tested for Xpert rifampicin resistance were used.
• Actionable-to-non-actionable result ratios and missed resistance were evaluated.

Main Results:

• Smear-negative specimens were more likely to yield non-actionable results for both first-line (MTBDRplus) and second-line (MTBDRsl) drug resistance assays.
• Excluding smear-negatives would lead to significant missed rapid diagnoses (e.g., 51% of isoniazid resistance).
• Testing smear-negatives with Xpert semi-quantitation category ≥ "medium" improved actionable-to-non-actionable ratios significantly while still detecting substantial resistance.

Conclusions:

• Xpert quantitative information can identify a subset of smear-negative TB specimens suitable for direct DST.
• This approach balances the need for actionable results with the risk of missed resistance.
• Findings support the rational expansion of direct DST to select smear-negative sputum samples.