PK/PD targets of amikacin and gentamicin in ICU patients

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 30 mg/kg of amikacin or 8 mg/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 ≥ 60 mg/L and ≥ 30 mg/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 ≥ 60 mg/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.