Pharmacokinetics of gentamicin and vancomycin during continuous venovenous hemofiltration in critically ill septic patients with acute kidney injury

Introduction

Acute kidney injury (AKI) is a common complication of critical illness and sepsis [1]. Dosing of antibacterial agents in septic patients is complicated by altered pharmacokinetics due to both acute renal failure and critical illness [2]. Current dosing regimens for administration of gentamicin and vancomycin to septic patients with AKI on continuous venovenous hemofiltration (CVVH) at a filtration rate of 45 ml/kg/hour are missing.

Methods

Seventeen septic patients with AKI treated with vancomycin and seven patients with gentamicin on CVVH were included. In the vancomycin group, patients received the first dose of 1.0 g intravenously followed by 1.0 g/12 hours if not adjusted. In the gentamicin group, patients received a loading dose of 240 mg followed by a maintenance dose every 24 hours. The vancomycin maintenance dose was optimized to achieve AUC_0-24/MIC ≥400 (Cmin >10 mg/l), gentamicin target was Cmax/MIC of 8 to 10. Maintenance doses were adjusted according to drug level simulation using a pharmacokinetic programme.

Results

The median vancomycin total clearance (Cltot) was 0.89 and 0.55 ml/minute/kg on the first and second day of the study. CRRT clearance accounted for about 50 to 60% of vancomycin Cltot found in a population with normal renal function (0.97 ml/minute/kg). Vancomycin serum concentrations after the first dose were below the required target of 10 mg/l as early as 6 hours in 10 patients. AUC_0-24/MIC ≥400 ratio was achieved in 67% of patients on the first day. The median gentamicin Cltot was 0.68 and 0.793 ml/minute/kg on the first and second day of the study. CRRT clearance accounted for about 50% of gentamicin Cltot found in a population without renal impairment (0.73 ml/minute/kg). The target Cmax/MIC ratio was achieved in 78% of patients after the first dose.

Conclusion

CVVH at a filtration rate of 45 ml/kg/hour leads to high removal of both antibiotics. Due to rapid change in patient's clinical status it was impossible to predict a fixed dosage regimen. We recommend administration of unreduced loading dose and: blood sampling as early as 6 hours after first vancomycin dose; blood sampling 30 to 60 minutes after gentamicin administration and before the next dose; and the maintenance dose should be based on drug-level monitoring.