TABLE 1.
Performance of whole-genome sequencing for prediction of resistance to first- and second-line Mycobacterium tuberculosis drugs
| Drug concn (mg/liter) | No. of isolates testing asa
: |
Sensitivity (% [95% CI])j | Specificity (% [95% CI]) | Predictive value (% [95 % CI]) |
|||||
|---|---|---|---|---|---|---|---|---|---|
| pR |
pS
|
||||||||
| gR | gS | gR | gS | Positive | Negative | Accuracy | |||
| Isoniazid 0.1 (n = 1,233) | 145 | 10b | 0 | 1,078 | 93.5 (88.5–96.9) | 100 (99.7–100) | 100 (97.5–100) | 99.1 (98.3–99.6) | 99.2 (98.5–99.6) |
| Rifampin 1 (n = 1,235) | 51 | 0 | 6c | 1,178 | 100 (93.0–100) | 99.5 (98.9–99.8) | 89.5 (78.5–96.0) | 100 (99.7–100) | 99.5 (99.0–99.8) |
| Ethambutol 5 (n = 1,230) | 18 | 2d | 15e | 1,195 | 90.0 (68.3–98.8) | 98.8 (98.0–99.3) | 54.5 (36.4–71.9) | 99.8 (99.4–100) | 98.6 (97.8–99.2) |
| Pyrazinamide 100 (n = 1,230) | 47 | 4f | 0 | 1,179 | 92.2 (81.1–97.8) | 100 (99.7–100) | 100 (92.5–100) | 99.7 (99.1–99.9) | 99.7 (99.2–99.9) |
| Ofloxacin 1 (n = 342) | 10 | 0 | 0 | 332 | 100 (69.2–100) | 100 (98.9–100) | 100 (69.2–100) | 100 (98.9–100) | 100 (98.9–100) |
| Moxifloxacin 0.5 (n = 57) | 4 | 0 | 4g | 49 | 100 (39.8–100) | 92.5 (81.8–97.9) | 50.0 (15.7–84.3) | 100 (92.7–100) | 93.0 (83.0–98.1) |
| Kanamycin 2.5 (n = 55) | 7 | 0 | 0 | 48 | 100 (59.0–100) | 100 (92.6–100) | 100 (59.0–100) | 100 (92.6–100) | 100 (93.5–100) |
| Amikacin 1 (n = 446) | 1 | 0 | 0 | 445 | 100 (2.5–100) | 100 (99.2–100) | 100 (2.5–100) | 100 (99.2–100) | 100 (99.2–100) |
| Capreomycin 2.5 (n = 55) | 6 | 0 | 0 | 49 | 100 (54.1–100) | 100 (92.7–100) | 100 (54.1–100) | 100 (97.7–100) | 100 (93.5–100) |
| Ethionamide 5 (n = 55) | 4 | 3h | 5i | 43 | 57.1 (18.4–90.1) | 89.6 (77.3–96.5) | 44.4 (13.7–78.8) | 93.5 (82.1–98.6) | 85.5 (73.3–93.5) |
a
pR, phenotype resistant; gR, genotype resistant; gS, genotype susceptible; pS, phenotype susceptible.
b
katG: Arg119Pro + Arg463Leu (1), Arg463Leu (3), Val1Gly + Glu3Val (1), wild type (WT) (5).
c
rpoB mutations related to rifampin susceptibility in MGIT and resistance in LJ (Löwenstein-Jensen medium)-DST.
d
embB: Leu499Pro + (C1602T) (1), WT (1).
e
Nine of 12 strains resistant to 2.5 mg/liter ethambutol.
f
pncA: Ala171Val (1), Asp8His (2); heteroresistance, pncA: Ala143Val (1).
g
Three strains resistant to 0.25 mg/liter moxifloxacin.
h
inhA: WT (3).
i
inhA: C-15T (4), C-15T + Ile194Thr (1).
j
CI, confidence interval.