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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 [1]. Despite several case reports on C/T pharmacokinetics in critically ill patients during continuous renal replacement therapy (CRRT) [2–4], the optimal dose in this clinical scenario still remains unclear [5]. A 68-year-old patient was admitted to our ICU with septic shock (nosocomial peritonitis) and anuric acute renal failure. Broad-spectrum antimicrobial therapy, including C/T and continuous venovenous hemodiafiltration (CVVHD), was initiated, using a polysulphone hemofilter (Fresenius, Germany) with blood flow, dialysate fluid, and replacement fluid rates of 100 mL/min, 2000 mL/h, and 1000mL/h. The patient received high C/T doses of C/T 2 g/1 g every 8 h (infused over 1 h) while receiving CVVHD, and became apyrexial 7 days after C/T treatment initiation, remaining fever-free for 14 days without any adverse effects related to this drug. Pre-filter and post-filter blood and ultradiafiltrate samples were obtained during the 8-h dosing interval after the fourth dose. Drug concentrations were measured by high-performance liquid chromatography. Figure 1 and Table 1 show preand post-filter plasma concentrations. Pharmacokinetic parameters were calculated (Table 2). Extraction ratios were high for both ceftolozane and tazobactam (49.3% ± 1.8% and 40.5% ± 4.5%). Mean C/T concentrations in the ultrafiltrate were 40 mg/L and 13.5 mg/L, respectively. We decided on a 3 g/iv dose every 8 h, taking into account two previous studies [3, 4] and a recent study which showed CRRT to be an independent predictor of clinical failure (OR 4.5, 95% CI 1.18– 17.39, p = 0.02) when C/T is administered at 1.5 g every 8 h [5]. 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

Optimizing ceftolozane-tazobactam dosage in critically ill patients during continuous venovenous hemodiafiltration