Table 1.
Pharmacokinetic/Pharmacodynamic indices of different antimicrobial classes and suggestions for dose adjustment in critically ill patients
| Antimicrobial class | PK/PD index | Clinical PK/PD target for efficacy | Clinical PK/PD threshold for toxicity | Adjustment in critically ill patients |
|---|---|---|---|---|
| Aminoglycosides | AUC0-24/MIC and Cmax/MIC | High, single dose and extended interval dosing | ||
| Amikacin | Cmax/MIC ≥ 8–10 | Cmin > 5 mg/L | ||
| Gentamicin/Tobramycin |
AUC0-24/MIC ≥ 110 Cmax/MIC ≥ 8–10 |
Cmin > 1 mg/L | ||
| Beta-lactams | % fT>MIC | Initial loading dose, followed by prolonged (continuous or extended) infusion | ||
| Carbapenems | 50–100% fT>MIC | Cmin > 44.5 mg/L | ||
| Cephalosporin | 45–100% fT>MIC | Cmin > 20 mg/L | ||
| Penicillins | 50–100% fT>MIC | Cmin > 361 mg/L | ||
| Daptomycin | AUC0-24/MIC | AUC0-24/MIC ≥ 666 mg/L | Cmin > 24 mg/L | Higher doses (10–12 mg/kg/day) to increase MIC (> 0.1 mg/L) |
| Fluoroquinolones | AUC0-24/MIC and Cmax/MIC |
AUC0-24/MIC ≥ 125–250 Cmax/MIC ≥ 12 |
Unclear | Loading dose with higher maintenance doses should be considered |
| Glycopeptides | AUC0-24/MIC | |||
| Teicoplanin | Cmin ≥ 10 mg/L | Unclear | Loading dose essential to reduce time to reach therapeutic exposures | |
| Vancomycin |
AUC0-24/MIC ≥ 400 Cmin > 10–20 mg/L |
AUC0-24 > 700 Cmin > 20 mg/L |
Consider loading dose of 25–30 mg/kg, followed by 15–20 mg/kg every 8–12 h if MIC > 1 mg/L and no renal impairment | |
| Linezolid |
AUC0-24/MIC 80–120 ≥ 85% T>MIC |
AUC0-24 > 300–350 Cmin > 7–10 |
Higher doses can be considered in ARDS and obese patients, or if MIC ≥ 2 mg/L | |
| Echinocandins | AUC0-24/MIC | AUC0-24/MIC ≥ 3000 | No data | Higher body weight may require higher dosing |
| Fluconazole | AUC0-24/MIC | AUC0-24/MIC ≥ 55–100 | Unclear | Loading dose of 12 mg/kg IV, followed by 6–12 mg/kg/day to reach therapeutic targets (AUC0-24/MIC 25–100), if no renal impairment |
| Voriconazole | AUC0-24/MIC | Cmin ≥ 1–2 mg/L | Cmin ≥ 4.5–6 mg/L | Loading dose of 6 mg/kg IV every 12 h for two doses, followed by 3–4 mg/kg IV every 12 h |
Adapted from [89]
AUC0-24/MIC ratio of the area under the concentration–time curve over a 24 h period to minimum inhibitory concentration, Cmax/MIC ratio of the maximum drug concentration to minimum inhibitory concentration, Cmin minimum drug concentration, fT>MIC duration of time that the free drug concentration remains above the minimum inhibitory concentration during a dosing interval, IV intravenously, MIC minimum inhibitory concentration, PK/PD pharmacokinetic/pharmacodynamic