TABLE 2.
Proportion of patients with trough of ≥3 μg/ml and mean nAUC (μg/ml) after simulation with Hartford nomogram-recommended extended interval
| Dosing interval | CLcr ≥ 60 ml/min (n = 189)b
|
CLcr > 30 to 59 mL/min (n = 92)b
|
||||
|---|---|---|---|---|---|---|
| Trough ≥3 μg/ml (n [%]) | nAUC,d mean (SD) | Trough <3 μg/ml and nAUC within reference rangee (n [%]) | Trough ≥3 μg/ml (n [%]) | nAUC,d mean (SD) | Trough <3 μg/ml and nAUC within reference rangee (n [%]) | |
| Eligible for q24h interval | ||||||
| Observeda | 9/153 (5.9%) | 234 (83) | 128/153 (83.7%) | 2/41 (4.9%) | 182 (54) | 32/41 (78%) |
| Simulated | –c | – | – | 2/41 (4.9%) | 166 (47) | – |
| P value | NDf | ND | ND | 1.000 | 0.156 | ND |
| Eligible for q36h interval | ||||||
| Observed | 6/22 (27.3%) | 312 (71) | 12/22 (54.5%) | 4/22 (18.2%) | 253 (73) | 16/22 (72.7%) |
| Simulated | 0/22 (0%) | 203 (36) | 22/22 (100%) | 1/22 (4.5%) | 153 (37) | 16/22 (72.7%) |
| P value | 0.021 | <0.001 | <0.001 | 0.345 | <0.001 | 1.000 |
| Eligible for q48h interval | ||||||
| Observed | 8/14 (57.1%) | 407 (102) | 5/14 (35.7%) | 21/29 (72.4%) | 323 (127) | 8/29 (27.6%) |
| Simulated | 0/14 (0%) | 205 (53) | 14/14 (100%) | 0/29 (0%) | 153 (56) | 23/29 (79.3%) |
| P value | 0.002 | <0.001 | <0.001 | <0.001 | <0.001 | <0.001 |
Observed AUC0–24h (μg · h/ml) and trough values based on q24h regimen received during the EPIC trial.
CLcr determined per EPIC trial protocol using the Cockcroft-Gault formula.
Simulation of nAUC and trough concentrations not performed, as patients were Hartford nomogram eligible for an interval that was utilized in EPIC (i.e., plazomicin 15 mg/kg q24h).
Interval-normalized AUC0–24h (nAUC, μg · h/ml) is AUC0–24h for q24h patients, AUC0–36h divided by 1.5 for q36h patients, and AUC0–48h divided by 2 for q48h patients.
The AUC reference range was defined as the 5th to 95th percentile AUC observed in the phase 3 cUTI trial (EPIC) (121 to 368 μg · h/ml).
ND, not done.