Antibiotics Removal during Continuous Renal Replacement Therapy in Septic Shock Patients: Mixed Modality Versus “Expanded Haemodialysis”

Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal.

This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF).

Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cl_eff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days.

HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = − 8.90 (95% CI − 12.9 to − 4.87), p < 0.001) and tazobactam (β = − 8.29 (95% CI − 13.5 to − 3.08), p = 0.002) and Cl_eff for each antibiotic (meropenem β = − 10,206 (95% CI − 14,787 to − 5787), p = 0.001); tazobactam (β = − 4551 (95% CI − 7781 to − 1322), p = 0.012); piperacillin (β = − 3913 (95% CI − 6388 to − 1437), p = 0.002), even if the carryover effect influenced the Cl_eff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = − 38.1 (95% CI − 47.9 to − 28.3), p < 0.001) and tazobactam (β = − 4.45 (95% CI − 6.17 to − 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type.

MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.