Table 1.
Studies reporting PK/PD indices from pre-clinical and clinical evaluations
| Antibiotic classifications |
Optimal PK/PD indices* | ||||||
|---|---|---|---|---|---|---|---|
| Pre-clinical studies | Clinical studies | ||||||
|
Concentration-
dependent |
Aminoglycosides | Maximal killing | AUC0-24/MIC 80-100 | 43 | Clinical Cure | Cmax/MIC 8-10 AUC/MIC >70 |
82-86 |
| Resistance suppression | Cmax/MIC 10-30 | 87 | Microbiological Cure | - | |||
| Time-dependent | Carbapenems | Maximal killing | 40% T>MIC | 88 | Clinical Cure | 75% T>MIC Cmin/MIC 5 |
89 |
| Resistance suppression | 16 × MIC Cmin/MIC >6.2 |
90
91 |
Microbiological Cure | 54% T>MIC | 17 | ||
| Cephalosporins | Maximal killing | 60-70% T>MIC | 11 | Clinical Cure | 100% T>MIC | 92 | |
| Resistance suppression | - | Microbiological Cure | 60-100% T>MIC 95% T>4.3×MIC |
16
93 |
|||
| Penicillins | Maximal killing | 40-50% T>MIC | 11 | Clinical Cure | - | ||
| Resistance suppression | 40-50% T>MIC | 94 | Microbiological Cure | 40-50% T>MIC | 95 | ||
|
Concentration
with time- dependence |
Fluoroquinolones | Maximal killing | AUC0-24/MIC >30-100 | 11, 96 | Clinical Cure | AUC0-24/MIC ≥125-250 Cmax/MIC ≥8 |
15, 86, 96 86,97, 98 |
| Resistance suppression | AUC0-24/MIC >160 AUC0-24/MPC ≥22 |
99, 100 101 |
Microbiological Cure | AUC0-24/MIC ≥34-125 Cmax/MIC ≥8 |
14, 102 86 |
||
| Vancomycin | Maximal killing | AUC0-24/MIC 86-460 | 103 | Clinical Cure | AUC0-24/MIC ≥400-450 | 20, 21 | |
| Resistance suppression | AUC0-24/MIC >200 | 104 | Microbiological Cure | AUC0-24/MIC ≥400 | 20 | ||
| Linezolid | Maximal killing | - | Clinical Cure | AUC0-24/MIC ≥85 85% T>MIC |
22 | ||
| Resistance suppression | - | Microbiological Cure | AUC0-24/MIC 80-120 85% T>MIC |
22 | |||
| Tigecycline | Maximal killing | 50% T>MIC | 105 | Clinical Cure | AUC0-24/MIC >12.8-17.9 f AUC0-24/MIC ≥0.9 |
106, 107 108 |
|
| Resistance suppression | - | Microbiological Cure | AUC0-24/MIC 6.9-17.9 | 109, 110 | |||
| Daptomycin | Maximal killing | AUC0-24/MIC 38-442 | 111, 112 | Clinical Cure | - | ||
| Resistance suppression | AUC0-24/MIC >200 | 104 | Microbiological Cure | - | |||
| Colistin | Maximal killing | AUC0-24/MIC 7-23 | 113, 114 | Clinical Cure | - | ||
| Resistance suppression | - | Microbiological Cure | - | ||||
Where the index is reported as a range, the data included may have been derived from different infection models with different bacteria. Specific data about the contributing values can be found in the associated references.
Data for the various indices has been reported in different studies according to total and free (unbound) drug. Where free concentrations have been reported, this is denoted using ‘f’
Legend: MIC – minimum inhibitory concentration; AUC0-24/MIC – ratio of area under the concentration time curve from 0-24 hours to MIC; Cmax/MIC – ratio of maximum concentration of antibiotic in a dosing interval to MIC; T>MIC – percentage of dosing interval that the antibiotic concentration is maintained above the MIC; AUC0-24/MPC; ratio of the AUC0-24 to mutant prevention concentration; Cmin – minimum concentration of antibiotic in a dosing interval; f – free or fraction of drug not bound to plasma proteins