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4CPS-209 Comparison of two pharmacokinetic/pharmacodynamic indices in critically ill patients treated with amikacin
  1. F Cajade1,
  2. I Beltrá-Picó2,
  3. S Ruiz-El Jerche2,
  4. A Viudez-Martínez2,
  5. A Bolea-Lacueva2,
  6. R Nalda-Molina3,
  7. A Ramón-López3,
  8. P Serrano-Más2
  1. 1Hospital Universitario De Santiago De Compostela, Farmacia Hospitalaria, Santiago De Compostela, Spain
  2. 2Hospital General Universitario De Alicante, Farmacia Hospitalaria, Alicante, Spain
  3. 3Universidad Miguel Hernández, Facultad De Farmacia, Elche, Spain


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.

Conflict of Interest No conflict of interest.

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