4CPS-209 Comparison of two pharmacokinetic/pharmacodynamic indices in critically ill patients treated with amikacin

Background and Importance Amikacin is commonly used as an empirical treatment for gram-negative infections in intensive care unit (ICU) patients. The pharmacokinetic/pharmacodynamic (PK/PD) index commonly used is the ratio maximal concentration: minimum inhibitory concentration (Cmax/MIC) and, to a lesser extent, the ratio area under the curve from 0 to 24h:MIC (AUC0– 24/MIC). Aim and Objectives To evaluate the PK/PD indices Cmax/MIC and AUC0–24/CMI for amikacin in critically ill patients. Material and Methods Patients admitted to a medical ICU with preserved renal function (CKD-EPI>60 ml/min) treated with empirical amikacin once-daily were included. Therapeutic Drug Monitoring (TDM) was carried out after the first dose (sample timing: Cmax and Cpost-8h, at 30 minutes and 8 hours respectively, after a 30-minute infusion). Targets for PK/PD Cmax/MIC and AUC0–24/MIC were 8–10 and 80, respectively. An empirical MIC of 4 mg/L was established for the calculation. Parametric AUC calculation was performed by empirical Bayesian estimation of pharmacokinetic parameter. Bayesian estimates were performed using PKS® software with a single compartment pharmacokinetic model. Patients were classified according to those who reached the target or not for both indices (Cmax/MIC and AUC0–24/MIC). Results Results expressed as median and percentile 25–75. Due to TDM, 100% of patients reached the therapeutic objective according to the Cmax/MIC index, although the percentage was reduced to 17% when the PK/PD index of efficacy was AUC0–24/MIC ratio (concordance index kappa=0.275; p≤0.05). To achieve the AUC0–24/MIC target, the required dose was estimated to be 1760 mg (1300–2270) (p=<0.05). Conclusion and Relevance No correlation between the PK/PD Cmax/CMI and AUC0–24/MIC indices was observed. To achieve the AUC0–24/MIC target, a significant dose increase is necessary compared to the doses required for Cmax/MIC. References and/or Acknowledgements Conflict of Interest No conflict of interest.