Vancomycin pharmacokinetics during high-volume continuous venovenous hemofiltration in critically ill septic patients

Abstract

Aims.To assess the influence of continuous venovenous hemofiltration (CVVH) at a filtration rate of 45 mL/kg/h on vancomycin pharmacokinetics in critically ill septic patients with acute kidney injury (AKI). Methods. Seventeen adult septic patients with acute kidney injury treated with CVVH and vancomycin were included. All patients received first dose of 1.0 g intravenously followed by 1.0 g/12 h if not adjusted. In sixteen patients vancomycin was introduced on the day of the start of CRRT therapy. Blood samples and ultrafiltrates were obtained before and 0.5, 1, 6 and 12 h after vancomycin administration. Results. On the first day, the median total vancomycin clearance (Cl tot ) was 0.89 mL/min/kg (range 0.31 -2.16). CRRT clearance accounted for around 50-60% of the total clearance of vancomycin found in a population with normal renal function (0.97 mL/min/kg). Vancomycin serum concentrations after the first dose were below the required target of 10 mg/L as early as 6 h in 10 patients, AUC 0-24 /MIC ≥ 400 ratio was achieved in 10 patients on the first day. Conclusions. CVVH at a filtration rate of 45 mL/kg/h leads to high and rapid extracorporeal removal of vancomycin in critically ill patients. Due to the rapid change in patient clinical status it was impossible to predict a fixed dosage regimen. We recommend blood sampling as early as 6 h after first vancomycin dose with maintenance dose based on vancomycin serum level monitoring.

How can we ensure effective antibiotic dosing in critically ill patients receiving different types of renal replacement therapy?

“…The vancomycin Sc is reported to be between 0.7 and 0.9 during CVVH/ CVVHDF for effluent flow rates between 20 and 50 mL/min (Chaijamorn et al, 2011;DelDot et al, 2004;Petejova et al, 2012b). RRT can significantly affect vancomycin clearance with large increases expected when higher effluent flow rates are used (N65 mL/min) (Escobar et al, 2014;Petejova et al, 2012b).…”

“…Numerous pharmacokinetic studies of vancomycin in critically ill patients receiving varying types of RRT have been published (Beumier et al, 2013;Chaijamorn et al, 2011;DelDot et al, 2004;Kielstein et al, 2006;Macias et al, 1991;Petejova et al, 2012bPetejova et al, , 2012c. The vancomycin Sc is reported to be between 0.7 and 0.9 during CVVH/ CVVHDF for effluent flow rates between 20 and 50 mL/min (Chaijamorn et al, 2011;DelDot et al, 2004;Petejova et al, 2012b).…”

Acute Kidney Injury in Septic Patients Treated by Selected Nephrotoxic Antibiotic Agents—Pathophysiology and Biomarkers—A Review

“…Many renally eliminated antimicrobial agents in these circumstances undergo changes in pharmacokinetics/pharmacodynamics parameters, including clearance, volume of distribution, binding to plasma proteins and elimination half-life. The dose adjustment has to be individualized according to serum concentration, to achieve the required pharmacodynamics parameters, drug efficacy and decrease the risk of toxicity [ 89 , 90 ]. Other preventive measures such as antioxidants in the case of antibiotic nephrotoxicity are still under investigation.…”

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

“…A 25-30 mg/kg loading dose is recommended for critically ill patients. However, increased clearance and the need for haemofiltration, both common in critically ill patients, are associated with low serum concentrations [49][50][51][52] and difficulty in early achievement of the target.…”