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

• Published in: Clinical pharmacokinetics Vol. 63; no. 8; pp. 1167 - 1176
• Main Authors: Ferrari, Fiorenza, Milla, Paola, Sartori, Marco, Zanza, Christian, Tesauro, Manfredi, Longhitano, Yaroslava, De Silvestri, Annalisa, Abbruzzese, Chiara, De Rosa, Silvia, Lassola, Sergio, Samoni, Sara, Brendolan, Alessandra, Zanella, Monica, Scaravilli, Vittorio, Grasselli, Giacomo, Arpicco, Silvia, Ronco, Claudio
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2024; Springer Nature B.V
• Subjects: Aged; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Antibiotics; Continuous Renal Replacement Therapy - methods; Cross-Over Studies; Drug dosages; Efficiency; Effluents; Female; Hemodiafiltration - methods; Hemodialysis; Humans; Internal Medicine; Kidney diseases; Male; Medicine; Medicine & Public Health; Membranes; Meropenem - administration & dosage; Meropenem - pharmacokinetics; Meropenem - therapeutic use; Middle Aged; Molecular weight; Original Research Article; Patients; Permeability; Pharmacology/Toxicology; Pharmacotherapy; Pilot Projects; Piperacillin - administration & dosage; Piperacillin - pharmacokinetics; Piperacillin - therapeutic use; Plasma; Renal Dialysis - methods; Renal replacement therapy; Sepsis; Shock, Septic - blood; Shock, Septic - drug therapy; Shock, Septic - therapy; Tazobactam - pharmacokinetics; Tazobactam - therapeutic use
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-024-01397-w

Background and Objective 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). Methods 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. Results 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. Conclusion MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.