Table 3.
Performance of the BD MAX Assay for the Detection of Drug Resistance Among Raw Specimens
| Microbiological Culture–Based DST | |||
|---|---|---|---|
| Analysis and BD MAX Result | Positive | Negative | Total (95% CI) |
| Any drug resistance (INH or RIF)a |
|||
| Positive | 24 | 7 | 31 (PPV, 77%) |
| Negative | 5 | 195 | 200 (NPV, 95%) |
| Total | 29 | 202 | 231 |
| Sensitivity | 83% (66–92%) | ||
| Specificity | 97% (93–98%) | ||
| INH resistance | |||
| Positive | 22b | 0 | 22 (PPV, 100%) |
| Negative | 5c | 205 | 210 (NPV, 98%) |
| Total | 27 | 205 | 232 |
| Sensitivity | 82% (63–92%) | ||
| Specificity | 100% (98–100%) | ||
| RIF resistance | |||
| Positive | 9 | 11d | 20 (PPV, 45%) |
| Negative | 1 | 211 | 212 (NPV, 99.5%) |
| Total | 10 | 222 | 232 |
| Sensitivity | 90% (60–98%) | ||
| Specificity | 95% (91–97%) | ||
Abbreviations: BD MAX, BD MAX multidrug-resistant tuberculosis assay; CI, confidence interval; DST, drug susceptibility testing; INH, isoniazid; NPV, negative predictive value; PPV, positive predictive value; RIF, rifampin.
aCases where BD MAX gave an RIF or INH Not Detected result or an RIF or INH Unreportable result were excluded. A total of 230 samples had reportable results for both RIF and INH resistance; 1 additional sample without INH results available is included, which had RIF resistance detected by BD MAX. Eight samples were resistant both for RIF and INH based on the DST. The BD MAX assay detected the dual resistance for 7 of 8 samples.
bAmong 22 INH-resistant isolates detected by BD MAX assay, mutations were detected in both inhA promoter and katG gene for 2 specimens, in inhA promoter alone for 4 specimens, and in katG gene alone for 16 specimens.
cAmong 5 isolates phenotypically resistant to INH but negative by BD MAX, sequencing of the targeted regions did not find mutations within katG or inhA promotor, suggesting resistance due to mutations outside the targeted regions for 3 isolates. For 1/5, sequencing suggested heteroresistance with a wild-type strain and a strain with a mutation in the inhA promoter may have been present. For 1/5, sequencing suggested heteroresistance with a wild-type strain and a strain with a mutation in the katG gene may have been present.
dEleven samples were resistant with BD MAX assay and sensitive by phenotypic DST. Among these 11, 6 were positive for RIF resistance by Xpert and bidirectional sequencing and 2 were found to have silent mutations. Another specimen gave a phenotypic DST error, but Xpert and bidirectional sequencing were resistant. When examined against a composite reference standard inclusive of Xpert and bidirectional sequencing (222 samples), sensitivity was 94% (16/17 [73–99%]) and specificity was 98% (200/205 [94–99%]).