Principles of antibacterial dosing in continuous renal replacement therapy

Abstract

Background: Appropriate antibacterial therapy is important to maximize patient survival in sepsis. Acute renal failure complicates optimal antibiotic administration.

Methods: MEDLINE search from 1986 to 2010 using the terms 'acute renal failure', 'pharmacokinetics', 'clearance', 'dosage', 'h(a)emofiltration', 'h(a)emodialysis', 'h(a)emodiafiltration', 'continuous renal replacement therapy', 'antibiotics', 'intensive care' and 'critically ill'.

Results: Maximal bacterial killing and minimization of side effects depend on achieving pharmacokinetic targets appropriate to the selected antibacterial agent. Volume of distribution and clearance may be altered by critical illness and/or acute kidney injury. Clearance is determined by nonrenal clearance, residual renal clearance and continuous renal replacement therapy dose. Sieving and saturation coefficients are membrane specific, but may be altered by changes in protein binding induced by critical illness. A significant proportion of studies failed to report the essential dataset required for adequate antibacterial dosage calculation.

Conclusions: Individualized dosing based on first principles may be the most appropriate method of dosing, particularly when enhanced by therapeutic drug monitoring.