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

UNLABELLED

Mycobacterium Growth Indicator Tube (MGIT) 960 culture is critical for tuberculosis (TB) drug susceptibility testing (DST) but is 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. 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), either at diagnosis (Cohort A) or during treatment monitoring (Cohort B). Future DSTs within 3 months served as a reference standard. We determined potential care cascade improvements. In Cohort A, 10% (66/650) of people had a contaminated culture; 89% (59/66) of contaminated growths were 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 two, one, and four people, respectively, this would be the first resistant result). In both cohorts, time-to-DST could improve by a median (IQR) of 22 (12-42) days. 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.

IMPORTANCE

Culture contamination is a common impediment to drug susceptibility testing for tuberculosis, the single biggest infectious cause of death globally. Xpert MTB/XDR is a World Health Organization-recommended rapid molecular test for second-line drug resistance. We evaluated Xpert MTB/XDR on contaminated liquid culture growth that would otherwise be discarded, with the people who provided these specimens potentially lost from care cascades. By applying Xpert MTB/XDR to contaminated growth in a high-volume programmatic laboratory, we found the number of people who had second-line DST improved, as did the number of resistant cases diagnosed and time to diagnosis. Furthermore, DST information was generated in people who otherwise would have had none. This approach can therefore reduce the effect of culture contamination on tuberculosis DST, permitting earlier diagnosis and effective treatment initiation and potentially ultimately contributing to improving clinical outcomes and reducing transmission of drug-resistant TB.