Beta-lactam antibiotic dosing during continuous renal replacement therapy: how can we optimize therapy?

Correct antibiotic treatment is of utmost importance to treat infections in critically ill patients, not only in terms of spectrum and timing but also in terms of dosing. However, this is a real challenge for the clinician because the pathophysiology (such as shock, augmented renal clearance, and multiple organ dysfunction) has a major impact on the pharmacokinetics of hydrophilic antibiotics. The presence of extra-corporal circuits, such as continuous renal replacement therapy, may further complicate this difficult exercise. Standard dosing may result in inadequate concentrations, but unadjusted dosing regimens may lead to toxicity. Recent studies confirm the variability in concentrations, and the wide variation in dialysis techniques used certainly contributes to these findings. Well-designed clinical studies are needed to provide the data from which robust dosing guidance can be developed. In the meantime, non-adjusted dosing in the first 1 to 2 days of antibiotic therapy during continuous renal replacement therapy followed by dose reduction later on seems to be a prudent approach.