Ceftolozane-tazobactam (C/T), the combination of a new cephalosporin with a classic β-lactamase inhibitor, is currently considered the most active betalactam antibiotic against P. aeruginosa. Despite several case reports on C/T pharmacokinetics in critically ill patients during continuous renal replacement therapy (CRRT), the optimal dose in this clinical scenario still remains unclear. Ceftolozane and tazobactam are small molecules with low plasma protein binding rates, causing most to be removed during CRRT. Despite the considerable C/T clearance observed in our patients during CVVHD, however, ceftolozane plasma concentrations remained above the MIC, for MICs of up to 8 μg/mL, throughout the dosing interval, assuming 20% protein binding. Given that C/T exhibits linear, dose-proportional pharmacokinetics, a standard C/T dose of 1 g/0.5 g would be expected to maintain ceftolozane levels above the MIC during the entire dosing interval, although tazobactam concentrations could be insufficient, even taking higher pre-filter rather than lower post-filter levels as representative of therapeutic serum levels.

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