Jason A Roberts,Marta Ulldemolins,Xin Liu,João P Baptista,Irma Bilgrami,Clement Boidin,Alexander Brinkmann,Pedro Castro,Gordon Choi,Louise Cole,Jan J De Waele,Renae Deans,Sine Donnellan,Glenn M Eastwood,Otto R Frey,Sylvain Goutelle,Rebecca Gresham,Janattul Ain Jamal,Gavin M Joynt,Salmaan Kanji,Stefan Kluge,Christina König,Vasilios P Koulouras,Melissa Lassig-Smith,Pierre-Francois Laterre,Anna Lee,Jean-Yves Lefrant,Katie Lei,Patricia Leung,Mireia Llaurado-Serra,Ignacio Martin-Loeches,Mohd Basri Mat Nor,Yugan Mudaliar,Marlies Ostermann,Sanjoy K Paul,Sandra L Peake,Jordi Rello,Darren M Roberts,Michael S Roberts,Brent Richards,Alejandro Rodríguez,Anka C Roehr,Claire Roger,Leonardo Seoane,Mahipal Sinnollareddy,Eduardo Sousa,Dolors Soy,Anna Spring,Therese Starr,Dianne Stephens,Fabio Silvio Taccone,Jane Thomas,John Turnidge,Miia Valkonen,Julie M Varghese,Steven C Wallis,Robert J Walker,Tricia Williams,Luke C Wilson,Xavier Wittebole,Daniel F B Wright,Xanthi T Zikou,Rinaldo Bellomo,Jeffrey Lipman,
{"title":"美罗培南和哌拉西林/他唑巴坦优化了危重患者接受肾脏替代治疗的给药方案。","authors":"Jason A Roberts,Marta Ulldemolins,Xin Liu,João P Baptista,Irma Bilgrami,Clement Boidin,Alexander Brinkmann,Pedro Castro,Gordon Choi,Louise Cole,Jan J De Waele,Renae Deans,Sine Donnellan,Glenn M Eastwood,Otto R Frey,Sylvain Goutelle,Rebecca Gresham,Janattul Ain Jamal,Gavin M Joynt,Salmaan Kanji,Stefan Kluge,Christina König,Vasilios P Koulouras,Melissa Lassig-Smith,Pierre-Francois Laterre,Anna Lee,Jean-Yves Lefrant,Katie Lei,Patricia Leung,Mireia Llaurado-Serra,Ignacio Martin-Loeches,Mohd Basri Mat Nor,Yugan Mudaliar,Marlies Ostermann,Sanjoy K Paul,Sandra L Peake,Jordi Rello,Darren M Roberts,Michael S Roberts,Brent Richards,Alejandro Rodríguez,Anka C Roehr,Claire Roger,Leonardo Seoane,Mahipal Sinnollareddy,Eduardo Sousa,Dolors Soy,Anna Spring,Therese Starr,Dianne Stephens,Fabio Silvio Taccone,Jane Thomas,John Turnidge,Miia Valkonen,Julie M Varghese,Steven C Wallis,Robert J Walker,Tricia Williams,Luke C Wilson,Xavier Wittebole,Daniel F B Wright,Xanthi T Zikou,Rinaldo Bellomo,Jeffrey Lipman, ","doi":"10.1007/s00134-025-08067-w","DOIUrl":null,"url":null,"abstract":"PURPOSE\r\nOptimal dosing of meropenem and piperacillin/tazobactam in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to variable pharmacokinetics. We aimed to develop generalisable optimised dosing recommendations for these antibiotics.\r\n\r\nMETHODS\r\nProspective, 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.\r\n\r\nRESULTS\r\nWe 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.\r\n\r\nCONCLUSION\r\nRRT 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.","PeriodicalId":13665,"journal":{"name":"Intensive Care Medicine","volume":"7 1","pages":""},"PeriodicalIF":21.2000,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy.\",\"authors\":\"Jason A Roberts,Marta Ulldemolins,Xin Liu,João P Baptista,Irma Bilgrami,Clement Boidin,Alexander Brinkmann,Pedro Castro,Gordon Choi,Louise Cole,Jan J De Waele,Renae Deans,Sine Donnellan,Glenn M Eastwood,Otto R Frey,Sylvain Goutelle,Rebecca Gresham,Janattul Ain Jamal,Gavin M Joynt,Salmaan Kanji,Stefan Kluge,Christina König,Vasilios P Koulouras,Melissa Lassig-Smith,Pierre-Francois Laterre,Anna Lee,Jean-Yves Lefrant,Katie Lei,Patricia Leung,Mireia Llaurado-Serra,Ignacio Martin-Loeches,Mohd Basri Mat Nor,Yugan Mudaliar,Marlies Ostermann,Sanjoy K Paul,Sandra L Peake,Jordi Rello,Darren M Roberts,Michael S Roberts,Brent Richards,Alejandro Rodríguez,Anka C Roehr,Claire Roger,Leonardo Seoane,Mahipal Sinnollareddy,Eduardo Sousa,Dolors Soy,Anna Spring,Therese Starr,Dianne Stephens,Fabio Silvio Taccone,Jane Thomas,John Turnidge,Miia Valkonen,Julie M Varghese,Steven C Wallis,Robert J Walker,Tricia Williams,Luke C Wilson,Xavier Wittebole,Daniel F B Wright,Xanthi T Zikou,Rinaldo Bellomo,Jeffrey Lipman, \",\"doi\":\"10.1007/s00134-025-08067-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"PURPOSE\\r\\nOptimal dosing of meropenem and piperacillin/tazobactam in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to variable pharmacokinetics. We aimed to develop generalisable optimised dosing recommendations for these antibiotics.\\r\\n\\r\\nMETHODS\\r\\nProspective, 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.\\r\\n\\r\\nRESULTS\\r\\nWe 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.\\r\\n\\r\\nCONCLUSION\\r\\nRRT 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.\",\"PeriodicalId\":13665,\"journal\":{\"name\":\"Intensive Care Medicine\",\"volume\":\"7 1\",\"pages\":\"\"},\"PeriodicalIF\":21.2000,\"publicationDate\":\"2025-08-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Intensive Care Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00134-025-08067-w\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Intensive Care Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00134-025-08067-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy.
PURPOSE
Optimal dosing of meropenem and piperacillin/tazobactam in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to variable pharmacokinetics. We aimed to develop generalisable optimised dosing recommendations for these antibiotics.
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.
期刊介绍:
Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.