{
  "abstract": "Background: Physiological alterations in patients with sepsis and trauma can influence antibiotic clearance, yet reliable predictors remain poorly defined. We aimed to investigate the determinants of piperacillin and cefazolin clearance in these populations to identify bedside indicators of subtherapeutic exposure.\n\nMethods: Prospective physiological and pharmacokinetic study in patients receiving piperacillin/tazobactam for sepsis or prophylactic cefazolin post-trauma. Patients also received intravenous sinistrin. Intensive pharmacokinetic sampling, cardiac output (CO) monitoring and four urinary creatinine clearance (uCLCR) measurements were performed. Data were analysed with non-compartmental pharmacokinetic methods, and linear and logistic regression.\n\nResults: We enrolled 49 septic and 28 trauma patients. Trauma patients were younger (33.5 vs. 46.5 years) and had higher uCLCR (155.5 vs. 107.5 mL/min). Linear regression identified that lower Sequential Organ Failure Assessment scores and an hyperdynamic state with higher CO and 2 and 8-h uCLCR were the strongest predictors of increased piperacillin total clearance; higher 2-h uCLCR and hypoalbuminemia were the main predictors for cefazolin total clearance. Sinistrin CL was a weak predictor. Logistic regression identified augmented renal clearance (8-h uCLCR > 130 mL/min) as the main risk factor for piperacillin subtherapeutic exposure (OR 10.9, p < 0.05), also when defined using the Cockcroft–Gault cut-off of 114.5 mL/min from ROC analysis.\n\nConclusions: In sepsis, low sickness severity and a hyperdynamic state with high cardiac output lead to increased uCLCR and high piperacillin clearance. In trauma, high cefazolin clearance occurs in the presence of an elevated uCLCR and hypoalbuminemia. These bedside physiological indicators, along with Cockcroft–Gault CLCR, may serve as early indicators of risk for subtherapeutic exposure.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13054-026-06239-8.",
  "abstract_shown": true,
  "affiliations": [
    "The Frazer Institute, Faculty of Health, Medicine, and Behavioural Sciences (HMBS), The University of Queensland, Brisbane, Australia",
    "Department of Infectious Diseases, Hospital Clinic de Barcelona, Barcelona, Spain",
    "Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain",
    "Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Melbourne, Australia",
    "Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia",
    "Department of Intensive Care Medicine, Clínico San Cecilio University Hospital, Instituto de Investigación Biosanitaria Ibs.GRANADA, Granada, Spain",
    "Department of Intensive Care Medicine, Princess Alexandra Hospital, Ipswich Road, Brisbane, QLD 4102 Australia",
    "Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC Australia",
    "School of Pharmacy and Biomedical Sciences, Adelaide University, Adelaide, Australia",
    "Therapeutics Research Centre, Basil Hetzel Institute for Translational Medical Research, The Queen Elizabeth Hospital, Adelaide, Australia",
    "Saw Swee Hock School of Public Health, ADVANCE-ID, National University of Singapore, Singapore, Singapore",
    "Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore",
    "Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia",
    "Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Brisbane, Australia",
    "Division of Anesthesia Critical Care, Pain and Emergency Medicine, UR-UM103 IMAGINE, Universite Montpellier, Nîmes University Hospital, Montpellier, France",
    "Department of Pharmacy Royal Brisbane and Women’s Hospital, Brisbane, Australia",
    "Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Marta Ulldemolins"
    },
    {
      "affs": [
        0
      ],
      "name": "Mohd Hafiz Abdul-Aziz"
    },
    {
      "affs": [
        0
      ],
      "name": "María Patricia Hernández-Mitre"
    },
    {
      "affs": [
        0
      ],
      "name": "Sazlyna Mohd Sazlly Lim"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Andrew A. Udy"
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    {
      "affs": [
        0,
        5
      ],
      "name": "Manuel Colmenero"
    },
    {
      "affs": [
        6
      ],
      "name": "Peter Kruger"
    },
    {
      "affs": [
        7
      ],
      "name": "Carl M. J. Kirkpatrick"
    },
    {
      "affs": [
        0,
        8,
        9
      ],
      "name": "Michael S. Roberts"
    },
    {
      "affs": [
        0
      ],
      "name": "Steven C. Wallis"
    },
    {
      "affs": [
        0,
        10,
        11
      ],
      "name": "David L. Paterson"
    },
    {
      "affs": [
        0,
        12,
        13,
        14
      ],
      "name": "Jeffrey Lipman"
    },
    {
      "affs": [
        0,
        12,
        14,
        15,
        16
      ],
      "name": "Jason A. Roberts"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dqhmt3aqdwg7q.bib",
  "cited_by": 0,
  "doi": "10.1186/s13054-026-06239-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737850/",
  "id": "dqhmt3aqdwg7q",
  "issns": [
    "1364-8535",
    "1466-609X"
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  "landing_url": "https://doi.org/10.1186/s13054-026-06239-8",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "2736|Antibiotics Pharmacokinetics and Efficacy"
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  "pdf_url": null,
  "pmcid": "PMC13737850",
  "pmid": "42983577",
  "published": "2026-08-06",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/dqhmt3aqdwg7q.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:57Z",
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      "field": "medicine",
      "origin": "openalex:2736|Antibiotics Pharmacokinetics and Efficacy",
      "subfield": "pharmacology-toxicology"
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  ],
  "title": "Physiological determinants of piperacillin and cefazolin clearance in septic and trauma patients",
  "title_text": "Physiological determinants of piperacillin and cefazolin clearance in septic and trauma patients",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:57Z",
  "url": "https://research.draconitic.com/paper/dqhmt3aqdwg7q",
  "venue": "Critical Care",
  "versions": []
}