Waste to Worth: A diagnostic accuracy of Xpert MTB/XDR on contaminated liquid cultures to salvage the detection of drug-resistant tuberculosis

Introduction: Mycobacterium Growth Indicator Tube (MGIT) 960 culture is critical for tuberculosis (TB) drug susceptibility testing (DST) but vulnerable to contamination. We evaluated the accuracy of Xpert MTB/XDR, a molecular DST for isoniazid, fluoroquinolone, amikacin, and ethionamide, on to-be-discarded contaminated growth. Methods: Xpert MTB/XDR was applied to acid-fast bacilli-negative contaminated cultures from sputum from people with rifampicin-resistant TB when Xpert MTB/XDR on sputum was unsuccessful (not resistant or susceptible for all drugs) 1) at diagnosis (Cohort A) or 2) during treatment monitoring (Cohort B). Future DSTs within three months served as a reference standard. We determined potential care cascade improvements. Results: In Cohort A, 10% (66/650) of people were culture-contaminated. 89% (59/66) were contaminated growth Xpert MTB/XDR TB-positive. Sensitivity and specificity for isoniazid, fluoroquinolone, amikacin, and ethionamide resistance were 100% [95% confidence interval (CI) 85, 100] and 100% (79, 100), 100% (59, 100) and 100% (89, 100), 100% (16, 100) and 100% (91, 100), and 100% (72, 100) and 96% (78, 100), respectively. In Cohort B, 22% (28/129) of people with a contaminated culture were Xpert MTB/XDR TB-positive. Of these, 57% (16/28), 7% (2/28), and 43% (12/28) were isoniazid-, fluoroquinolone-, and ethionamide-resistant (in 2, 1, and 4 people respectively, this would be the first resistant result). In both cohorts, time-to-DST could improve a median (IQR) of 22 (12-42) days. Conclusion: Xpert MTB/XDR on contaminated MGIT960 cultures had high sensitivity and specificity for DST. This approach could mitigate culture contamination’s negative effects and improve gaps in the drug-resistant TB diagnostic cascade.