title: Ceftolozane/Tazobactam Pharmacokinetics in a Critically Ill Adult Receiving Continuous Renal Replacement Therapy.
abstract: 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.
authors.affiliation: Department of Pharmacy, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
authors.forename: Derek N
authors.initials: DN
authors.lastname: Bremmer
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut.|Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
authors.affiliation: Department of Pharmacy, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
authors.forename: Pam
authors.initials: P
authors.lastname: Burcham
authors.affiliation: Division of Nephrology, Department of Internal Medicine, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
authors.forename: Anil
authors.initials: A
authors.lastname: Chunduri
authors.affiliation: Division of Nephrology, Department of Internal Medicine, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Shidham
authors.affiliation: Department of Pharmacy, The Ohio State University, Wexner Medical Center, Columbus, Ohio.
authors.forename: Karri A
authors.initials: KA
authors.lastname: Bauer
keywords: ceftolozane; hemodiafiltration; pharmacokinetics; renal replacement therapy; tazobactam