Vezava meropenema, piperacilina in vankomicina na hemoadsorbent Cytosorb

Rogelj Meljo, Neža (author), Vovk, Tomaž (mentor), Kenda, Sara (comentor)

Za zdravljenje sepse se uporabljajo protimikrobne učinkovine, med katere sodijo meropenem, piperacilin in vankomicin. V zadnjem času se pri zdravljenju sepse uporablja tudi hemoadsorbent CytoSorb, ki odstranjuje vnetne mediatorje iz krvi. Raziskovalci so ugotovili, da se na CytoSorb vežejo tudi nekatere protimikrobne učinkovine. V magistrski nalogi smo določali in vitro vezavo meropenema, piperacilina in vankomicina na CytoSorb. V goveji krvi smo uravnali vrednost hematokrita in koncentracijo albumina ter tako posnemali pogoje v krvi septičnih bolnikov. Čaše s prilagojeno goveje krvjo smo postavili na magnetna mešala, jih segrevali na 37 °C ter dodali terapevtske koncentracije izbranih protimikrobnih učinkovin in CytoSorb. Poskus smo izvedli v dveh delih. V prvem delu smo imeli težave s ponovljivostjo in doseganjem terapevtskih koncentracij protimikrobnih učinkovin. Poskus smo prilagodili in med drugim povečali količino dodanega CytoSorba. Tekom poskusa smo s tekočinsko kromatografijo visoke ločljivosti spremljali plazemske koncentracije protimikrobnih učinkovin in ocenili njihovo vezavo na CytoSorb. Med poskusom smo spremljali tudi hemolizo, ki ni presegla 0,8 %. Potrdili smo, da delež hemolize ni bil odvisen od izbrane protimikrobne učinkovine in dodatka CytoSorba. V drugem delu poskusa smo spremljali tudi koncentracijo albumina, ki je po 2 urah padla za 19 %. Po prilagoditvi poskusa sta bili ponovljivost in točnost ustreznejši. Ugotovili smo, da koncentracija CytoSorba v krvi vpliva na obseg vezave protimikrobnih učinkovin na CytoSorb. 6 ur po dodatku 1,0 g CytoSorba v 100 mL krvi se je koncentracija vankomicina znižala za 68 %, koncentracija piperacilina za 56 %, koncentracija meropenema pa za 41 %. 3 ure po dodatku 6,2 g CytoSorba v 100 mL krvi je koncentracija piperacilina je padla za 97 %, koncentracija vankomicina za 91 %, koncentracija meropenema pa za 84 %. Izračunali smo tudi očistke za posamezne protimikrobne učinkovine. Pri dodatku 6,2 g CytoSorba je bil največji očistek piperacilina (0,526 L/h), sledila sta očistek vankomicina (0,372 L/h) in očistek meropenema (0,358 L/h). Primerjava z očistki iz podobnih raziskav je pokazala, da so bili očistki v našem poskusu nekoliko nižji, vendar pa raziskave niso bile povsem primerljive. Za potrditev rezultatov bi morali narediti več ponovitev poskusa. Naše ugotovitve potrjujejo, da se protimikrobne učinkovine vežejo na CytoSorb, kar s kliničnega stališča pomeni, da bi morali pri bolnikih, ki se zdravijo s CytoSorbom, povečati odmerke protimikrobnih učinkovin.

• Language: Slovenian
• Keywords: meropenem, piperacilin, vankomicin, CytoSorb, hemoadsorpcija, sepsa
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-150351
• Publication date in RUL: 16.09.2023

Secondary language

• Language: English
• Title: Binding of meropenem, piperacillin and vancomycin to Cytosorb hemoadsorbent

Abstract

Antimicrobial agents, including meropenem, piperacillin, and vancomycin, are used for the treatment of sepsis. Recently, the hemoadsorbent CytoSorb has also been used in sepsis treatment to remove inflammatory mediators from blood. Researchers have found that some antimicrobial agents also bind to CytoSorb. In this thesis, we studied the in vitro binding of meropenem, piperacillin, and vancomycin to CytoSorb. We adjusted hematocrit and albumin levels in bovine blood to simulate conditions in the blood of septic patients. We placed beakers with modified bovine blood on magnetic stirrers, heated them to 37 °C, and added therapeutic concentrations of selected antimicrobial agents and CytoSorb. The experiment was conducted in two parts. In the first part, we had problems with reproducibility and achieving therapeutic concentrations of antimicrobial agents. We adjusted the experiment, which included increasing the amount of added CytoSorb. During the experiment, we monitored plasma concentrations of antimicrobial agents using high-performance liquid chromatography and assessed their binding to CytoSorb. We also monitored hemolysis, which did not exceed 0.8 %. We confirmed that specific antimicrobial agents and CytoSorb addition did not affect hemolysis. In the second part of the experiment, albumin concentrations were also monitored, which decreased by 19 % after 2 hours. Reproducibility and accuracy improved after we adjusted the experiment. We established that the concentration of CytoSorb in blood affects the extent of binding of antimicrobial agents to CytoSorb. 6 hours after adding 1.0 g of CytoSorb in 100 mL of blood, the concentration of vancomycin decreased by 68 %, the concentration of piperacillin by 56 %, and the concentration of meropenem by 41 %. 3 hours after adding 6.2 g of CytoSorb in 100 mL of blood, the concentration of piperacillin decreased by 97 %, the concentration of vancomycin by 91 %, and the concentration of meropenem by 84 %. We also calculated clearance for each antimicrobial agent. With addition of 6.2 g of CytoSorb, the highest clearance was that of piperacillin (0.526 L/h), followed by vancomycin (0.372 L/h) and meropenem (0.358 L/h). Comparison with clearances from similar studies showed that the clearances in our experiment were slightly lower, but the studies were not entirely comparable. To validate the results, additional repetitions of the experiment are necessary. Our findings confirm that antimicrobial agents bind to CytoSorb, which, from a clinical perspective, implies that doses of antimicrobial agents should be increased for patients undergoing CytoSorb treatment.

• Keywords: meropenem, piperacillin, vancomycin, CytoSorb, hemoadsorption, sepsis