To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt

• Pharmacokinetics vary markedly in critically ill patients receiving CRRT.
• Prescribe initial dose of antibiotics based on volume of distribution.
• Prescribe subsequent doses based on CRRT and non-CRRT clearance.
• Unlike other antibiotics, clearance of colistin by CRRT is greater than by healthy kidney.
• Therapeutic drug monitoring is useful to further individualize drug dosing.

Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing.