Table 2.
Diagnostic Accuracy of Genotypic Drug Susceptibility Testing by Next-Generation Sequencing Compared With Liquid Culture (mycobacteria growth indicator tube - MGIT) as the Reference Standard
| Resistant Phenotype (MGIT) | Susceptible Phenotype (MGIT) | Phenotype Not Applicable | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Genotype (Next-Generation Sequencing) | R | U | S | Total | R | U | S | Total | R | U | S | Total | Sensitivity, % (95% CI) | Specificity, % (95% CI) | Positive Predictive Value, % (95% CI) | Negative Predictive Value, % (95% CI) |
| Rifampicin | 64 | 0 | 0 | 64 | 6 | 0 | 0 | 6 | 0 | 0 | 0 | 0 | a | a | a | a |
| Rifabutin | 56 | 0 | 0 | 56 | 13 | 0 | 0 | 13 | 1 | 0 | 0 | 1 | 100.0 (92.0–100.0) | 0.0 (0.028.3) | 81.2 (69.6–89.2) | n/a |
| Isoniazid | 68 | 0 | 0 | 68 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | a | a | a | a |
| Bedaquiline | 1 | 1 | 0 | 2 | 1 | 6 | 61 | 68 | 0 | 0 | 0 | 0 | b | b | b | b |
| Levofloxacin | 17 | 0 | 2 | 19 | 4 | 2 | 45 | 51 | 0 | 0 | 0 | 0 | 89.5 (65.5–98.2) | 91.8 (79.5–97.4) | 81 (57.4–93.7) | 95.7 (84.3–99.3) |
| Moxifloxacin | 15 | 0 | 2 | 17 | 6 | 2 | 45 | 53 | 0 | 0 | 0 | 0 | 88.2 (62.3–97.9) | 88.2 (75.4–95.1) | 71.4 (47.7–87.8) | 95.7 (84.3–99.3) |
| Linezolid | 2 | 0 | 0 | 2 | 1 | 0 | 67 | 68 | 0 | 0 | 0 | 0 | b | b | b | b |
| Clofazimine | 2 | 1 | 0 | 3 | 0 | 8 | 59 | 67 | 0 | 0 | 0 | 0 | b | b | b | b |
| Cycloserinec | 2 | 0 | 0 | 2 | 2 | 10 | 56 | 68 | 0 | 0 | 0 | 0 | b | b | b | b |
| Pyrazinamide | 45 | 0 | 3 | 48 | 1 | 1 | 20 | 22 | 0 | 0 | 0 | 0 | 93.8 (81.8–98.4) | 95.2 (74.1–99.8) | 97.8 (87.0–99.9) | 87.0 (65.3–96.6) |
| Prothionamidec | 28 | 3 | 0 | 31 | 5 | 13 | 21 | 39 | 0 | 0 | 0 | 0 | 100.0 (85.0–100.0) | 80.8 (60.0–92.7) | 84.8 (67.3–94.3) | 100.0 (80.8–100.0) |
| Amikacin | 7 | 0 | 1 | 8 | 3 | 0 | 59 | 62 | 0 | 0 | 0 | 0 | 87.5 (46.7–99.3) | 95.2 (85.6–98.7) | 70.0 (35.4–91.9) | 98.3 (89.9–99.9) |
| Delamanid | 0 | 0 | 2 | 2 | 0 | 8 | 60 | 68 | 0 | 0 | 0 | 0 | b | b | b | b |
| Para-aminosalicylic acid c | 7 | 2 | 2 | 11 | 5 | 6 | 48 | 59 | 0 | 0 | 0 | 0 | 77.8 (40.2–96.1) | 90.6 (78.6–96.5) | 58.3 (28.6–83.5) | 96.0 (85.1–99.3) |
| Ethambutolc | 41 | 1 | 0 | 42 | 16 | 4 | 7 | 27 | 1 | 0 | 0 | 1 | 100.0 (89.3–100.0) | 30.4 (14.1–53.0) | 71.9 (58.3–82.6) | 100.0 (56.1–100.0) |
| Overall | 355 | 8 | 12 | 375 | 64 | 60 | 549 | 673 | 2 | 0 | 0 | 2 | 96.7 (94.2–98.2) | 89.6 (86.8–91.8) | 84.7 (80.8–88.0) | 97.9 (96.2–98.8) |
Detected and/or predicted resistance is considered a positive test result, and susceptibility is considered a negative test result. Uncharacterized mutations were not considered in the performance calculation.
Abbreviations: CI, confidence interval; MGIT, mycobacteria growth indicator tube; R, resistant, S, susceptible, U, unknown.
aPerformance not calculated as drug resistance was an inclusion criterion.
bPerformance not calculated due to low prevalence of resistance.
cWith reservation as no reliable critical concentrations/breakpoints exist for cycloserine, para-aminosalicylic acid, ethambutol, and protionamide, drug susceptibility testing in mycobacteria growth indicator tube is not recommended.