Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database

Logre, Elsa; Enser, Maya; Tanaka, Sébastien; Dubert, Marie; Claudinon, Aurore; Grall, Nathalie; Mentec, Hervé; Montravers, Philippe; Pajot, Olivier

BACKGROUND: Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (C(max)) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the C(max) should be 64–80 mg/L. This objective is based on clinical breakpoints and not on measured MIC. This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target C(max)/MIC ≥ 8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections. METHODS: Retrospective analysis from February 2016 to December 2017 of a prospective database conducted in 2 intensive care units (ICU). All patients with documented severe GNB infections treated with amikacin (single daily dose of 25 mg/kg of total body weight (TBW)) with both MIC and C(max) measurements at first day of treatment (D1) were included. Results are expressed in n (%) or median [min–max]. RESULTS: 93 patients with 98 GNB-documented infections were included. The median C(max) was 55.2 mg/L [12.2–165.7] and the median MIC was 2 mg/L [0.19–16]. C(max)/MIC ratio ≥ 8 was achieved in 87 patients (88.8%) while a C(max) ≥ 64 mg/L was achieved in only 38 patients (38.7%). Overall probability of PK/PD target attainment was 93%. No correlation was found between C(max)/MIC ratio and clinical outcome at D8 and D28. CONCLUSION: According to PK/PD parameters observed in our study, single daily dose of amikacin 25 mg/kg of TBW appears to be sufficient in most critically ill patients treated for severe GNB infections.