Table 3.
Target-based next-generation sequencing performance by drug in patients enrolled for next-generation sequencing using pDST as the reference standard, Mumbai, India, 2019–2020
| A) All pDST reporting resistance compared to the specimen’s genotype per each drug | |||||
| Drug | Phenotypic-resistant vs. GenoType | ||||
|
| |||||
| Resistant | Heteroresistant | Susceptible | Uncharacterised | Total | |
|
| |||||
| INH | 130 | 1 | 1 | 132 | |
| RIF | 123 | 2 | 125 | ||
| EMB | 89 | 4 | 15 | 108 | |
| PZA | 90 | 12 | 3 | 105 | |
| SM | 110 | 2 | 2 | 113 | |
| FQ | 88 | 6 | 4 | 98 | |
| KM | 19 | 1 | 11 | 2 | 33 |
| AMK | 14 | 2 | 16 | ||
| CPM | 8 | 5 | 1 | 14 | |
| ETH | 49 | 16 | 14 | 79 | |
| LZD | 2 | 2 | 4 | ||
| CFZ | 2 | 4 | 6 | ||
|
| |||||
| All pDST reporting susceptible compared to the specimen’s genotype per each drug | |||||
|
| |||||
| Drug | Phenotypic-susceptible vs. GenoType | ||||
|
| |||||
| Resistant | Heteroresistant | Susceptible | Incomplete coverage | Total | |
|
| |||||
| INH | 1 | 15 | 16 | ||
| RIF | 11 | 3 | 14 | 28 | |
| EMB | 19 | 25 | 44 | ||
| PZA | 2 | 40 | 42 | ||
| SM | 3 | 31 | 34 | ||
| FQ | 1 | 55 | 56 | ||
| KM | 3 | 109 | 4 | 116 | |
| AMK | 129 | 3 | 132 | ||
| CPM | 8 | 119 | 7 | 134 | |
| ETH | 3 | 64 | 64 | ||
| LZD | 1 | 142 | 1 | 142 | |
| CFZ | 6 | 1 | 134 | 134 | |
| B) Sensitivity and specificity is reported in this table under two considerations 1) including uncharacterised variants and 2) excluding the uncharacterised variants in the calculations. | ||||
|
| ||||
| Drug | Including uncharacterised variants | Excluding uncharacterised variants | ||
|
|
|
|||
| Sensitivity % (95% CI) | Specificity % (95% CI) | Sensitivity % (95% CI) | Specificity % (95% CI) | |
|
| ||||
| INH | 99.2 (95.8–99.9) | 93.2 (71.7–98.9) | 99.2 (95.8–99.9) | 93.2 (71.7–98.9) |
| RIF* | 100.0 97.0–100) | 56.6 (37.0–73.3) | 100.0 97.0–100) | 56.6 (37.0–73.3) |
| EMB*† | 100.0 (96.4–100) | 56.8 (42.4–70.3) | 100.0 (95.9–100) | 56.8 (42.4–70.3) |
| PZA† | 88.6 (81.1–93.3) | 95.2 (84.2–98.7) | 88.2 (80.5–93.1) | 95.2 (84.2–98.7) |
| SM | 98.2 (93.8–99.5) | 91.2 (77.0–97.0) | 98.2 (93.7–99.5) | 91.2 (77.0–97.0) |
| FQ | 95.7 (89.4–98.3) | 98.2 (90.6–99.7) | 95.7 (89.4–98.3) | 98.2 (90.6–99.7) |
| KM | 65.6 (48.3–79.6) | 97.3 (92.4–99.1) | 63.3 (45.5–78.1) | 97.3 (92.4–99.1) |
| AMK | 87.5 (64.0–96.5) | 100.0 (97.1–100) | 87.5 (64.0–96.5) | 100.0 (97.1–100) |
| CPM | 64.3 38.8–83.7) | 93.7 (88.1–96.8) | 61.5 (35.5–82.3) | 93.7 (88.1–96.8) |
| ETH† | 79.7 (69.7–87,1) | 95.5 (87.6–98.5) | 75.4 (63.7–84.2) | 95.5 (87.6–98.5) |
| LZD‡ | 50.0 (15.0. 85.0) | 99.3 (96.2–99.9) | 50.0 (15.0. 85.0) | 99.3 (96.2–99.9) |
| CFZ‡ | 33.3 (9.7–70) | 96.8 (90.1–98.0) | 33.3 (9.7–70) | 96.8 (90.1–98.0) |
*
Low specificity due to low level resistance (borderline).
†
High level of uncharacterised variants identified.
‡
Limited information on resistance variants or other resistance mechanisms.
pDST = phenotypic drug susceptibility testing; INH = isoniazid; RIF = rifampicin; EMB = ethambutol; PZA = pyrazinamide; SM = streptomycin; FQ = fluoroquinolone; KM = kanamycin; AMK = amikacin; CPM = capreomycin; ETH = ethionamide; LZD = linezolid; CFZ = clofazimine; CI = confidence interval.