Table 3.
Relation between antituberculosis drug plasma concentrations and culture results at weeks 4 and 8a
| Characteristicb | GM (IQR) |
OR (95% CI)c for positive culture | |
|---|---|---|---|
| Positive culture | Negative culture | ||
| Wk 4 (n) | 56 | 108 | |
| Isoniazid C2 h (mg/liter) | 1.3 (0.9–2.2) | 1.5 (1.0–2.2) | 0.76 (0.49–1.18)* |
| Rifampin C2 h (mg/liter) | 6.5 (5.1–10.8) | 6.7 (4.8–11.8) | 0.95 (0.66–1.36)* |
| Pyrazinamide C2 h (mg/liter) | 35.4 (31.8–40.9) | 37.0 (33.2–41.5) | 0.80 (0.55–1.15)* |
| Low plasma concentrations | |||
| No drug | 5 (36) | 9 (64) | 1.00 |
| One drug | 18 (35) | 34 (65) | 0.95 (0.28–3.27) |
| Two drugs | 21 (37) | 36 (63) | 1.05 (0.31–3.55) |
| All three drugs | 12 (29) | 29 (71) | 0.75 (0.21–2.69) |
| Very low plasma concentrations | |||
| No drug | 24 (33) | 49 (67) | 1.00 |
| One drug | 23 (30) | 53 (70) | 0.89 (0.44–1.77) |
| Two drugs | 8 (57) | 6 (43) | 2.72 (0.85–8.73) |
| All three drugs | 1 (100) | 0 (0) | NA |
| Wk 8 (n) | 11 | 142 | |
| Isoniazid C2 h (mg/liter) | 1.3 (0.9–2.4) | 1.4 (0.9–2.2) | 0.88 (0.39–1.96)* |
| Rifampin C2 h (mg/liter) | 6.5 (6.1–12.1) | 6.8 (5.0–11.7) | 0.95 (0.47–1.90)* |
| Pyrazinamide C2 h (mg/liter) | 38.5 (34.0–44.6) | 36.5 (32.4–41.0) | 1.38 (0.65–2.93)* |
| Low plasma concentrations | |||
| No drug | 2 (15) | 11 (85) | 1.00 |
| One drug | 3 (6) | 46 (94) | 0.36 (0.05–2.41) |
| Two drugs | 4 (7) | 50 (93) | 0.44 (0.07–2.71) |
| All three drugs | 2 (5) | 35 (95) | 0.31 (0.04–2.50) |
| Very low plasma concentrations | |||
| No drug | 5 (7) | 65 (93) | 1.00 |
| One drug | 4 (6) | 64 (94) | 0.81 (0.21–3.16) |
| Two drugs | 2 (14) | 12 (86) | 2.17 (0.38–12.49) |
| All three drugs | 0 (0) | 1 (100) | NA |
Data are presented as the GM (IQR) or number (percentage) unless stated otherwise in column 1. Pharmacokinetic parameters were log transformed. OR, odds ratio; CI, confidence interval; C2 h, plasma concentration 2 h after dose administration; NA, not assessed.
For “low plasma concentrations,” isoniazid C2 h at <3 mg/liter, rifampin C2 h at <8 mg/liter, and pyrazinamide C2 h at <35 mg/liter were considered low. For “very low plasma concentrations,” isoniazid C2 h at <1.5 mg/liter, rifampin C2 h at <4 mg/liter, and pyrazinamide C2 h at <20 mg/liter were considered very low. “No drug” served as a reference category.
*, That is, the OR for an interquartile range increase in C2 h, i.e., an increase in C2 h values from the 25th percentile to the 75th percentile of observed C2 h values (interquartile OR), based on continuous drug concentration data.