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1.
Clin Pharmacokinet ; 63(8): 1167-1176, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39102092

RESUMO

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 (Cleff) 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 (ß = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (ß = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cleff for each antibiotic (meropenem ß = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (ß = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (ß = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (ß = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (ß = - 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.


Assuntos
Antibacterianos , Terapia de Substituição Renal Contínua , Estudos Cross-Over , Meropeném , Diálise Renal , Choque Séptico , Humanos , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Antibacterianos/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Choque Séptico/terapia , Choque Séptico/tratamento farmacológico , Choque Séptico/sangue , Projetos Piloto , Terapia de Substituição Renal Contínua/métodos , Diálise Renal/métodos , Meropeném/uso terapêutico , Meropeném/administração & dosagem , Meropeném/farmacocinética , Tazobactam/uso terapêutico , Tazobactam/farmacocinética , Piperacilina/farmacocinética , Piperacilina/uso terapêutico , Piperacilina/administração & dosagem , Hemodiafiltração/métodos
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