Abstract
BackgroundAminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (Cmax) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the Cmax 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 Cmax/MIC ≥ 8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections.MethodsRetrospective 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 Cmax measurements at first day of treatment (D1) were included. Results are expressed in n (%) or median [min–max].Results93 patients with 98 GNB-documented infections were included. The median Cmax was 55.2 mg/L [12.2–165.7] and the median MIC was 2 mg/L [0.19–16]. Cmax/MIC ratio ≥ 8 was achieved in 87 patients (88.8%) while a Cmax ≥ 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 Cmax/MIC ratio and clinical outcome at D8 and D28.ConclusionAccording 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.
Highlights
Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (Cmax) reaches eight to tenfold the minimal inhibitory concentration (MIC)
A single daily dose of amikacin (25 mg/kg of total body weight (TBW)) appears to be sufficient in most critically ill patients treated for severe Gram-negative bacilli (GNB) infections
PK/PD parameters were not different whether the clinical outcome was favorable or poor on D8 (Additional file 1: Table S2), and between patients alive or dead on D28 (Additional file 1: Table S3). In this prospective database performed in critically ill patients with documented GNB infections and receiving a 25 mg/kg single daily dose of amikacin, the overall probability of target attainment Peak serum concentration (Cmax)/MIC ratio ≥ 8 was 93% according to our Cmax and MIC distributions
Summary
Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (Cmax) reaches eight to tenfold the minimal inhibitory concentration (MIC). This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target Cmax/MIC ≥ 8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections. Optimal anti-GNB activity of amikacin is achieved when peak serum concentration (Cmax) reach eight to tenfold the minimal inhibitory concentration (MIC) [3]. Logre et al Ann. Intensive Care (2020) 10:75 which the bacteria have intermediate susceptibility based on clinical breakpoints defined by EUCAST), the target Cmax should be 64–80 mg/L as recommended by French guidelines on aminoglycosides use [4, 5]. In order to optimize the Cmax/MIC ratio, it is suggested to increase amikacin loading dose up to 30 mg/kg/ day of total body weight (TBW) for severe patients [5]
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