Evidence map›Paper›PMID 40801954›Full record

Observational studyIntensive care medicine2025

Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy.

Jason A Roberts, Marta Ulldemolins, Xin Liu, João P Baptista, Irma Bilgrami, Clement Boidin, Alexander Brinkmann, Pedro Castro, Gordon Choi, Louise Cole and 55 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Intensive care medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
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  4. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

65 authors.

Jason A Roberts *University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia. j.roberts@uq.edu.au.ORCID 0000-0001-6218-435X
Marta Ulldemolins *University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia.
Xin LiuUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia.
João P BaptistaIntensive Care Medicine Department, Hospitais da Universidade de Coimbra (HUC), ULS Coimbra, Coimbra, Portugal.
Irma BilgramiIntensive Care Unit, Royal Darwin Hospital, Tiwi, NT, Australia.
Clement BoidinUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia.
Alexander BrinkmannDepartment of Anesthesia and Critical Care Medicine, General Hospital of Heidenheim, Heidenheim, Germany.
Pedro CastroMedical Intensive Care Unit, Institut Clínic de Medicina I Dermatologia, Hospital Clínic de Barcelona, Barcelona, Spain.
Gordon ChoiDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
Louise ColeSchool of Medicine, University of Sydney, Sydney, Australia.
Jan J De WaeleDepartment of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.
Renae DeansUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia.
Sine DonnellanDepartment of Nephrology, Dunedin Public Hospital, Dunedin, New Zealand.
Glenn M EastwoodDepartment of Intensive Care, Austin Hospital, Heidelberg, Australia.
Otto R FreyDepartment of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany.
Sylvain GoutelleLaboratoire de Biométrie et Biologie Évolutive, Université Claude Bernard Lyon 1, UMR CNRS 5558, Lyon, France.
Rebecca GreshamIntensive Care Unit, Nepean Hospital, Sydney, Australia.
Janattul Ain JamalDepartment of Clinical Pharmacy, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Malaysia.
Gavin M JoyntDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
Salmaan KanjiDepartment of Pharmacy, The Ottawa Hospital, Ottawa, Canada.
Stefan KlugeDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Christina KönigDepartment of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Vasilios P KoulourasIntensive Care Unit Department, University Hospital of Ioannina, Ioannina, Greece.
Melissa Lassig-SmithDepartment of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Pierre-Francois LaterreIntensive Care Unit, Clinique Universitaire St Luc, UCLouvain, Brussels, Belgium.
Anna LeeDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
Jean-Yves LefrantDivision of Anesthesia Critical Care, Pain and Emergency Medicine, Nîmes University Hospital, UR-UM103 IMAGINE, Universite Montpellier, Montpellier, France.
Katie LeiGuy's and St Thomas Hospital, London, UK.
Patricia LeungDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
Mireia Llaurado-SerraDepartment of Fundamental and Clinical Care Nursing, Faculty of Nursing, Bellvitge Campus, University of Barcelona, Barcelona, Spain.
Ignacio Martin-LoechesMultidisciplinary Intensive Care Research Organization (MICRO), St James Hospital, Dublin, Ireland.
Mohd Basri Mat NorKulliyyah of Medicine, International Islamic University Malaysia, Kuantan Campus, Kuantan, Pahang, Malaysia.
Yugan MudaliarCritical Care Intensive Care Unit Services, Westmead Public/Private Hospitals, Sydney, Australia.
Marlies OstermannGuy's and St Thomas Hospital, London, UK.
Sanjoy K PaulCollege of Life Sciences, University of Leicester, Leicester, UK.
Sandra L PeakeDepartment of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville, Australia.
Jordi RelloDivision of Anesthesia Critical Care, Pain and Emergency Medicine, Nîmes University Hospital, UR-UM103 IMAGINE, Universite Montpellier, Montpellier, France.
Darren M RobertsNew South Wales Poisons Information Centre, Sydney Children's Hospitals Network, Westmead, Australia.
Michael S RobertsTherapeutics Research Centre, UQCCR and Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Brent RichardsIntensive Care Unit, Gold Coast University Hospital, Gold Coast, Australia.
Alejandro RodríguezCentro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Anka C RoehrDepartment of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany.
Claire RogerDivision of Anesthesia Critical Care, Pain and Emergency Medicine, Nîmes University Hospital, UR-UM103 IMAGINE, Universite Montpellier, Montpellier, France.
Leonardo SeoaneFaculty of Medicine, The University of Queensland, New Orleans, USA.
Mahipal SinnollareddyTherapeutics Research Centre, UQCCR and Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Eduardo SousaIntensive Care Medicine Department, Hospitais da Universidade de Coimbra (HUC), ULS Coimbra, Coimbra, Portugal.
Dolors SoyInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Anna SpringIntensive Care Unit, Naval and Veterans Hospital of Athens, Athens, Greece.
Therese StarrDepartment of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Dianne StephensIntensive Care Unit, Royal Darwin Hospital, Tiwi, NT, Australia.
Fabio Silvio TacconeDepartment of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium.
Jane ThomasIntensive Care Unit, Royal Darwin Hospital, Tiwi, NT, Australia.
John TurnidgeSchool of Biological Sciences, University of Adelaide, Adelaide, Australia.
Miia ValkonenIntensive Care Medicine, Department of Perioperative, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Julie M VargheseUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia.
Steven C WallisUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia.
Robert J WalkerDepartment of Nephrology, Dunedin Public Hospital, Dunedin, New Zealand.
Tricia WilliamsDepartment of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville, Australia.
Luke C WilsonDepartment of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Xavier WitteboleIntensive Care Unit, Clinique Universitaire St Luc, UCLouvain, Brussels, Belgium.
Daniel F B WrightSydney Pharmacy School, University of Sydney, Sydney, Australia.
Xanthi T ZikouIntensive Care Unit Department, Army Share Fund Hospital Athens, Athens, Greece.
Rinaldo BellomoDepartment of Intensive Care, Austin Hospital, Heidelberg, Australia.
Jeffrey LipmanUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Herston, Brisbane, Australia.
SMARRT Study Collaborators

Funding

National Health and Medical Research Council APP1044941National Health and Medical Research Council APP2009736Research Grants Council of the Hong Kong Special Administrative Region, China CUHK 14106614
6 · The paper itself

Abstract

purposeOptimal 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.

methodsProspective, 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.

resultsWe 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.

conclusionRRT 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.

Indexed as

Anti-Bacterial AgentsCritical IllnessMeropenemPiperacillin, Tazobactam Drug CombinationRenal Replacement TherapyAgedFemaleHumansIntensive Care UnitsMaleMiddle AgedMonte Carlo MethodProspective StudiesAnti-Bacterial AgentsMeropenemPiperacillin, Tazobactam Drug CombinationCritically ill patientsDosing nomogramsMeropenemPharmacokineticsPiperacillin/tazobactamRenal replacement therapy

Identifiers

PMID40801954
PMCPMC12405346

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.