Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Roberts Jason A, Ulldemolins Marta, Liu Xin, Baptista João P, Bilgrami Irma, Boidin Clement, Brinkmann Alexander, Castro Pedro, Choi Gordon, Cole Louise, De Waele Jan J, Deans Renae, Donnellan Sine, Eastwood Glenn M, Frey Otto R, Goutelle Sylvain, Gresham Rebecca, Jamal Janattul Ain, Joynt Gavin M, Kanji Salmaan, Kluge Stefan, König Christina, Koulouras Vasilios P, Lassig-Smith Melissa, Laterre Pierre-Francois, Lee Anna, Lefrant Jean-Yves, Lei Katie, Leung Patricia, Llaurado-Serra Mireia, Martin-Loeches Ignacio, Nor Mohd Basri Mat, Mudaliar Yugan, Ostermann Marlies, Paul Sanjoy K, Peake Sandra L, Rello Jordi, Roberts Darren M, Roberts Michael S, Richards Brent, Rodríguez Alejandro, Roehr Anka C, Roger Claire, Seoane Leonardo, Sinnollareddy Mahipal, Sousa Eduardo, Soy Dolors, Spring Anna, Starr Therese, Stephens Dianne, Taccone Fabio Silvio, Thomas Jane, Turnidge John, Valkonen Miia, Varghese Julie M, Wallis Steven C, Walker Robert J, Williams Tricia, Wilson Luke C, Wittebole Xavier, Wright Daniel F B, Zikou Xanthi T, Bellomo Rinaldo, Lipman Jeffrey, SMARRT Study Collaborators
Аннотация
METHODS: Prospective, multinational pharmacokinetic study including patients requiring various forms of RRT. Independent population PK models were developed, externally validated and applied to perform Monte Carlo dosing simulations using Monolix and Simulx. We calculated the probability that these dosing regimens achieved standard and high therapeutic unbound antibiotic concentrations over 100% of the dosing interval for the treatment of Enterobacterales and Pseudomonas aeruginosa.
RESULTS: We enrolled 300 patients from 22 intensive care units across 12 countries receiving continuous veno-venous haemodialysis (13.0%), haemofiltration (23.3%), haemodiafiltration (48.4%) or sustained low-efficiency dialysis (15.3%). Models were developed using data from 234 patients (8322 samples) and validated with 66 additional patients (560 samples). Predictive performance was high, with mean prediction errors of - 5.2% for meropenem and - 16.9% for piperacillin. Dosing simulations showed that meropenem and piperacillin/tazobactam dosing requirements were dependent on urine output and RRT intensity and duration (p < 0.05). In all scenarios, extended/continuous infusions led to a better achievement of effective concentrations with lower daily doses compared to short infusion. Dosing nomograms were developed to inform dosing for different RRT settings, urine outputs, and target concentrations.
CONCLUSION: RRT intensity and duration and urine output determine meropenem and piperacillin/tazobactam dosing requirements in critically ill patients receiving RRT. Extended/continuous infusions facilitate the attainment of effective concentrations.