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.

How to optimise antimicrobial prescriptions in the Intensive Care Unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics

“…The effect of RRT on drug dosing requirements is heterogeneous and depends on many factors related to the patient, the drug and the dialysis settings [27]. The clinical example (see later) illustrates in detail how these factors can be identified and applied in the setting of continuous renal replacement therapy (CRRT).…”

Antifungal Dosing in Dialysis and Continuous Renal Replacement Therapy

“…Drugs with a large pharmacokinetic Vd (≥1 L/kg) are usually found in greater concentrations in tissues rather than circulating in the plasma and are therefore not accessible to the RRT device circuit, whereas drugs with a lower Vd are more often distributed in the blood and extracellular fluids, where they may be more readily presented to the dialyzer membrane and subsequently removed. When all factors are taken into account, the drugs that are most likely to undergo significant removal during any type of RRT are those that are primarily renally eliminated, of small molecular weight, not highly protein-bound, and characterized by a small Vd [4][5][6]7…”

“…RRT-specific factors also highly influence the degree of drug removal; some of the more important ones include the type of RRT procedure, membrane characteristics, duration of the procedure, and the flow rates of blood, dialysate, and ultrafiltrate [4][5][6]7••]. The efficiency of dialyzer membranes is described by the relative rate of transfer of small solutes across the membrane as blood is passed across it.…”

Article de synthèse: La suppléance rénale en cas de maladie grave

“…There are proposed methods for estimating CL (EC) and appropriate drug dosing for patients receiving RRT, mostly focused on antimicrobials. [59][60][61][62] One such method is based on calculation of the fractional CL (EC) of a drug related to total body clearance, accounting for CL from non-renal (NR) and residual renal function (R), represented by:…”