Pharmacokinetics and Dialytic Clearance of Ceftazidime-Avibactam in a Critically Ill Patient on Continuous Venovenous Hemofiltration [PublishAheadOfPrint]

Ceftazidime-avibactam 1.25 g every 8 hours was used to treat multi-drug resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Pre-filter plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 hours along with post-filter and ultrafiltrate concentrations at hours 2 and 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were C_max 61.10 and 14.54 mg/L, C_min 31.96 and 8.45 mg/L, t_1/2 6.07 and 6.78 hours, V_ss 27.23 and 30.81 liters, CL_ss 2.87 and 2.95 L/h, and AUC_0-8 347.87 and 85.69 mg ⋅ h/L. Concentrations of ceftazidime in plasma exceeded the ceftazidime-avibactam MIC (6 mg/L) throughout the 8 hour dosing interval. Mean CVVH extraction ratio % for ceftazidime and avibactam, respectively, were 14.44% and 11.53% and mean sieving coefficients were 0.96 and 0.93, respectively. The calculated mean clearance of ceftazidime by CVVH was 1.64 L/h and for avibactam it was 1.59 L/h, representing 57.1% of the total clearance of ceftazidime and 54.3% of the total clearance of avibactam. Further data including multiple patients and dialysis modes are needed to verify the optimal dosing strategy of ceftazidime-avibactam during critical illness and CVVH.

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