Ceftolozane/Tazobactam Pharmacokinetics in a Critically Ill Adult Receiving Continuous Renal Replacement Therapy

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Limited data are available on ceftolozane/tazobactam dosing in patients receiving continuous renal replacement therapy (CRRT). Thus we performed a pharmacokinetic analysis of intravenous ceftolozane/tazobactam in a critically ill patient receiving CRRT at our medical center. A 47-year-old critically ill man with multidrug-resistant Pseudomonas aeruginosa pneumonia, bacteremia, and osteomyelitis was receiving ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) every 8 hours while receiving continuous venovenous hemodiafiltration (CVVHDF). After the fifth dose of ceftolozane/tazobactam, plasma samples were obtained at 1-, 2-, 4-, 6-, and 8-hour time points. Two additional post-hemodialysis filter plasma samples were obtained to assess CVVHDF clearance. The maximum and minimum plasma concentrations for ceftolozane were 163.9 μg/ml and 79.4 μg/ml, respectively. The area under the plasma concentration–time curve from 0–8 hours (AUC0–8) was 689 μg hour/ml; the plasma half-life was 13.3 hours. The ceftolozane CVVHDF clearance and total clearance were 2.4 L/hour and 2.9 L/hour, respectively. Compared with a patient with normal renal function, this patient receiving CVVHDF had decreased ceftolozane clearance. A ceftolozane/tazobactam dosage of 1.5 g every 8 hours should adequately achieve a desired drug concentration above the minimum inhibitory concentration of 8 μg/ml for the treatment of pneumonia. Additional pharmacokinetic data are needed to confirm our results and for alternative forms of CRRT.

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