PK/PD targets of amikacin and gentamicin in ICU patients

Abstract

Objectives: We aimed to evaluate the probability to achieve PK-PD targets in patients with sepsis hospitalized in the intensive care unit (ICU) after a single dose of 30mg/kg of amikacin or 8mg/kg of gentamicin.

Patients and methods: This single-center prospective study included 138 ICU patients with severe sepsis or septic shock with an indication for intravenous amikacin (N=89) or gentamicin (N=49). Maximum concentration (C_max) was measured 30 minutes after infusion completion. PK/PD objectives were respectively C_max≥60mg/L and ≥30mg/L for amikacin and gentamicin for empirical therapy, and a C_max/MIC ratio≥8, as per French guidelines.

Results: The median Simplified Acute Physiology Score II was 43 and ICU case fatality rate was 34.8%. A causative bacterial agent was identified in 94 patients (68.1%). Three pathogens had acquired aminoglycoside resistance and 15 were naturally resistant. The targeted C_max for the first dose was achieved in 53 patients (59.6%) receiving amikacin, and one (2.2%) patient receiving gentamicin. C_max/MIC ratio≥8 was obtained in all patients infected with susceptible pathogens (N=72). Factors associated with C_max≥60mg/L of amikacin in multivariate analysis were dose per kg of adapted body weight (OR=1.39, P<0.001) and renal clearance estimated with CKD-EPI formula (OR=0.98, P=0.003).

Conclusions: Despite high doses, amikacin and gentamicin first C_max remain dramatically low in ICU patients. However, an adequate C_max/MIC ratio was reached in all patients.

Keywords: Amikacin; Gentamicin; Intensive care unit; PK/PD.