PK/PD study of ceftazidime/avibactam in patients with severe intra-abdominal infections treated by continuous veno–venous hemofiltration

Abstract Purpose: To investigate the pharmacokinetics (PK) of ceftazidime/avibactam and optimize dosing regimens in patients with severe intra-abdominal infection (sIAI) receiving continuous veno–venous hemofiltration (CVVH). Methods: Seven patients with sIAI treated with ceftazidime/avibactam and CVVH were enrolled. Blood samples were collected at pre-dose and post-dose (2, 3, 4, 6, and 8 h) during hemodynamic stability. Plasma concentrations were measured, and PK parameters were calculated. Monte Carlo simulations (MCSs) were used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) for different dosing regimens. Results: CVVH increased the clearance (CL) significantly (ceftazidime: 2.46 ± 0.29 vs. 0.9 ± 0.11 L/h; avibactam: 2.89 ± 0.41 vs. 1.09 ± 0.08 L/h, p < 0.001). For the target of 100%fT ≥ MIC + 100%fT ≥ CT = 1.0 mg/L, during CVVH, PTA > 90% at MIC ≤ 8 mg/L. Outside CVVH, PTA > 90% at MIC ≤ 16 mg/L, and only 3000 mg + 750 mg q8h achieved PTA > 90% at MIC = 64 mg/L. For the target of 100%fT ≥ 4× MIC (ceftazidime) + 100%fT ≥ CT = 4.0 mg/L (avibactam), during CVVH, PTA > 90% at MIC ≤ 2 mg/L. Outside CVVH, PTA > 90% at MIC ≤ 4 mg/L, and only 3000 mg + 750 mg q8h achieved PTA > 90% at MIC = 16 mg/L. No regimen met the optimal dosing criteria for this target. Conclusion: CVVH enhanced the CL significantly. Dosing should be “individualized” based on the MIC and patient-specific factors.