PK/PD of single-dose amikacin in emergency department patients with severe sepsis/shock: should we apply the ICU-based higher loading dose?

Introduction

Studies in the ICU showed that a single amikacin dose of ≥25 mg/kg should be used in conditions of increased distribution volume (Vd) such as severe sepsis/shock [1]. However, no data are available for emergency department (ED) patients in the early phase of sepsis/septic shock. The purpose of this study was to determine whether a single amikacin dose of 25 versus 15 mg/kg results in PK/PD target attainment for ED patients.

Methods

ED patients with severe sepsis/shock were randomly treated with a single amikacin dose of 25 versus 15 mg/kg. Blood samples were collected at +1 (peak), +6 hours and +24 hours (trough) after the start of infusion. Primary outcome was PK/PD target attainment defined as a peak/MIC >8, corresponding with both actual MIC values documented from isolated pathogens, as well as EUCAST susceptibility breakpoints for Enterobacteriaceae and P. aeruginosa; that is, 8 mg/l. Noncompartmental analysis was used to calculate PK parameters.

Results

During a study duration of 20 months, 50 patients were enrolled in each dosing regimen resulting in 100 peak concentrations, 92 and 88 +6 hours and +24 hours concentrations respectively. Target attainment using local MIC values (median 2 mg/l, documented in 56 isolated Gram-negative pathogens) was achieved in 95% in both groups (P = 0.98). Using EUCAST susceptibility breakpoints, the target was attained in 76% versus 40% in the 25 versus 15 mg/kg group, respectively (P < 0.0001). Single-dose PK parameters are displayed in Table 1 and compared with the ones reported in the ICU [1].

Table 1

Conclusion

The EUCAST-based PK/PD target was only attained in 76% of patients treated with 25 mg/kg. However, in contrast to ICU patients, the majority of ED patients are treated for community-acquired infections, so MIC values are significantly lower than the EUCAST susceptibility breakpoints, warranting PK/PD target attainment in both 25 and 15 mg/kg dosing regimens when local epidemiology is taken into account.