Table 4.
Plazomicin, tigecycline, and meropenem pharmacodynamic exposure compared with microbiological and clinical response
| Patient | Plazomicin AUC/MIC (MIC)a | Adjunct antibiotic | Tigecycline fAUC/MIC (MIC) | Meropenem fT > MIC (MIC) | Tigecycline/meropenem PD threshold achievedb | Microbiological response at TOC | Clinical response at 28 days |
|---|---|---|---|---|---|---|---|
| 1 | 3333 (0.12) | Meropenem | N/A | 0% (64) | No | Eradication | Cure |
| 2 | 3708 (0.12) | Meropenem | N/A | 0% (64) | No | Eradication | Cure |
| 3 | 1048 (0.25) | Tigecycline | 1.79 (0.5) | N/A | Yes | Eradication | Cure |
| 4c | 461 (0.5) | Tigecycline and meropenem | 1.08 (0.5) | 0% (128) | Yes/no | Presumed eradication | Cure |
| 5 | 476 (0.5) | Tigecycline | 1.05 (2) | N/A | Yes | Presumed persistence | Failure |
| 6 | 836 (0.5) | Tigecycline | 1.33 (1) | N/A | Yes | Eradication | Cure |
| 7 | 278 (0.5) | Tigecycline | 0.54 (1) | N/A | No | Eradication | Cure |
| 8 | 733 (0.25) | Tigecycline | 2.16 (0.5) | N/A | Yes | Eradication | Failure |
| 9 | 3003 (0.12) | Tigecycline | 1.78 (0.5) | N/A | Yes | Eradication | Cure |
| 10 | 480 (0.5) | Tigecycline | 1.03 (1) | N/A | Yes | Eradication | Cure |
| 11 | 1027 (0.25) | Tigecycline | 0.83 (1) | N/A | No | Eradication | Cure |
| 12 | 1022 (0.25) | Tigecycline | 1.03 (1) | N/A | Yes | Eradication | Cure |
| 15 | 622 (0.25) | Meropenem | N/A | 0% (256) | No | Eradication | Failure |
| 16 | 583 (0.25) | Tigecycline | 2.08 (0.5) | N/A | Yes | Presumed persistence | Failure |
| 17 | 1844 (0.12) | Tigecycline | 0.59 (2) | N/A | No | Eradication | Cure |
N/A not available, MIC minimum inhibitory concentration, AUC/MIC total drug area under the curve/MIC, fAUC/MIC free area under the curve/MIC, fT > MIC free time above the MIC as a percent of the dosing interval, PD pharmacodynamics, TOC test of cure
aPlazomicin AUC/MIC ≥ 85 on day 1 was defined as the pharmacodynamic target
bfAUC/MIC ≥ 0.9 at steady-state was defined as the pharmacodynamic target for tigecycline. For meropenem, a threshold ≥ 40% fT > MIC on day 1 was defined as the pharmacodynamic target
cPatient 4 received meropenem for study days 1–4, followed by tigecycline for study days 4–14; this patient is counted as exposure threshold achieved due to attainment of tigecycline PD target