International journal of antimicrobial agents · 2026
Validation of limited sampling strategies for polymyxin B therapeutic drug monitoring in critical care.
СтатьяВалидационное исследованиеНазвание и аннотация: Перевод в очереди
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Surovoy Yury A, Galvidis Inna A, Alimov Akmal I, Tsarenko Sergei V, Burkin Maksim A
Аннотация
OBJECTIVE: To validate previously developed limited sampling strategies (LSSs) for polymyxin B (PMB) therapeutic drug monitoring (TDM) in critically ill patients with sepsis on renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO).
METHODS: Two compartmental pharmacokinetic models were produced in 27 patients with sepsis, 11 patients on RRT, and 14 patients on ECMO, and then used to simulate 1000 individual pharmacokinetic curves for each group. LSS using one to three timepoints were developed using a Bayesian approach.
RESULTS: The LSSs based on three timepoints allowed a precise prediction of AUC0-12h of PMB given as a 60-min infusion in patients with sepsis and patients receiving ECMO (R2 >0.95), as well as in patients receiving RRT (R2 >0.9) provided 60-min PMB infusion. Among the patients with sepsis, ECMO, and RRT, the three-point C5min, C2h, C11h model provided the most consistent results, with an R2 of 0.96, 0.97, and 0.9, respectively. Among the two-point models, C2h, C11h demonstrated the best performance, with an R2 of 0.93, 0.93, and 0.85, respectively. Depending on the model in patients with sepsis and patients receiving ECMO, the probability of reaching the target was 84-91% (compared with ∼60% without TDM), while in patients on RRT this value reached 85-87% (compared with ∼40% without TDM).
CONCLUSIONS: The C5min, C2h, C11h and C2h, C11h sampling schemes allowed adequate prediction of PMB exposure within a 3-h timeframe, providing steady-state conditions where C0h equals C11h. A new clinically oriented approach was used to demonstrate a 25-45% increase in reaching the target with TDM.
METHODS: Two compartmental pharmacokinetic models were produced in 27 patients with sepsis, 11 patients on RRT, and 14 patients on ECMO, and then used to simulate 1000 individual pharmacokinetic curves for each group. LSS using one to three timepoints were developed using a Bayesian approach.
RESULTS: The LSSs based on three timepoints allowed a precise prediction of AUC0-12h of PMB given as a 60-min infusion in patients with sepsis and patients receiving ECMO (R2 >0.95), as well as in patients receiving RRT (R2 >0.9) provided 60-min PMB infusion. Among the patients with sepsis, ECMO, and RRT, the three-point C5min, C2h, C11h model provided the most consistent results, with an R2 of 0.96, 0.97, and 0.9, respectively. Among the two-point models, C2h, C11h demonstrated the best performance, with an R2 of 0.93, 0.93, and 0.85, respectively. Depending on the model in patients with sepsis and patients receiving ECMO, the probability of reaching the target was 84-91% (compared with ∼60% without TDM), while in patients on RRT this value reached 85-87% (compared with ∼40% without TDM).
CONCLUSIONS: The C5min, C2h, C11h and C2h, C11h sampling schemes allowed adequate prediction of PMB exposure within a 3-h timeframe, providing steady-state conditions where C0h equals C11h. A new clinically oriented approach was used to demonstrate a 25-45% increase in reaching the target with TDM.