Impact of pediatric continuous renal replacement therapy parameters on meropenem, piperacillin, and tazobactam pharmacokinetics: an in vitro model.

Background: Limited data exist on how continuous renal replacement therapy (CRRT) affects antimicrobial dosing in pediatric patients. This study examined the impact of pediatric CRRT parameters on the pharmacokinetics (PK) of meropenem, piperacillin, and tazobactam using an in vitro CRRT model.

Research design and methods: An in vitro CRRT model with a pediatric ST60 circuit was used to assess antimicrobial clearance during continuous veno-venous hemodialysis (CVVHD) or hemofiltration (CVVH). Antimicrobials were administered intermittently or continuously, with samples taken pre- and post-filter, and from the effluent. The model tested two conditions: 1) off treatment (0 mL/kg/h), and 2) an elimination phase, with CRRT flow rates ranging from 40 to 400 mL/kg/h.

Results: Clearance of meropenem, piperacillin, and tazobactam increased significantly with higher dialyzate/ultrafiltration flow rates (p < 0.001). Median clearance rates differed significantly by CRRT flow rates and modality (p < 0.001). Under CVVHD, the saturation coefficient (Sa) decreased with increasing dialyzate flow rates, while under CVVH, the sieving coefficient (Sc) remained stable regardless of ultrafiltration rates.

Conclusions: The clearance of low protein-binding, low molecular weight antimicrobials increases with higher CRRT effluent flow rates, with modality-specific differences in clearance dynamics.