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Peer-reviewedCC BY-NC-ND 4.0Critical Care

Physiological determinants of piperacillin and cefazolin clearance in septic and trauma patients

  • Marta Ulldemolins1,2,3
  • Mohd Hafiz Abdul-Aziz1
  • María Patricia Hernández-Mitre1
  • Sazlyna Mohd Sazlly Lim1
  • Andrew A. Udy4,5
  • Manuel Colmenero1,6
  • Peter Kruger7
  • Carl M. J. Kirkpatrick8
  • Michael S. Roberts1,9,10
  • Steven C. Wallis1
  • David L. Paterson1,11,12
  • Jeffrey Lipman1,13,14,15
1 more authors
  • Jason A. Roberts1,13,15,16,17
17 affiliations
  1. 1The Frazer Institute, Faculty of Health, Medicine, and Behavioural Sciences (HMBS), The University of Queensland, Brisbane, Australia
  2. 2Department of Infectious Diseases, Hospital Clinic de Barcelona, Barcelona, Spain
  3. 3Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
  4. 4Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital, Melbourne, Australia
  5. 5Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
  6. 6Department of Intensive Care Medicine, Clínico San Cecilio University Hospital, Instituto de Investigación Biosanitaria Ibs.GRANADA, Granada, Spain
  7. 7Department of Intensive Care Medicine, Princess Alexandra Hospital, Ipswich Road, Brisbane, QLD 4102 Australia
  8. 8Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC Australia
  9. 9School of Pharmacy and Biomedical Sciences, Adelaide University, Adelaide, Australia
  10. 10Therapeutics Research Centre, Basil Hetzel Institute for Translational Medical Research, The Queen Elizabeth Hospital, Adelaide, Australia
  11. 11Saw Swee Hock School of Public Health, ADVANCE-ID, National University of Singapore, Singapore, Singapore
  12. 12Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  13. 13Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia
  14. 14Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Brisbane, Australia
  15. 15Division of Anesthesia Critical Care, Pain and Emergency Medicine, UR-UM103 IMAGINE, Universite Montpellier, Nîmes University Hospital, Montpellier, France
  16. 16Department of Pharmacy Royal Brisbane and Women’s Hospital, Brisbane, Australia
  17. 17Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia
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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.

Methods: 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.

Results: 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.

Conclusions: 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.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13054-026-06239-8.

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Cite

BibTeXRIS
BibTeX
@article{ulldemolins2026physiological,
  title = {{Physiological determinants of piperacillin and cefazolin clearance in septic and trauma patients}},
  author = {Marta Ulldemolins and Mohd Hafiz Abdul-Aziz and María Patricia Hernández-Mitre and Sazlyna Mohd Sazlly Lim and Andrew A. Udy and Manuel Colmenero and Peter Kruger and Carl M. J. Kirkpatrick and Michael S. Roberts and Steven C. Wallis and David L. Paterson and Jeffrey Lipman and Jason A. Roberts},
  journal = {Critical Care},
  year = {2026},
  month = aug,
  doi = {10.1186/s13054-026-06239-8},
  url = {https://doi.org/10.1186/s13054-026-06239-8},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Physiological determinants of piperacillin and cefazolin clearance in septic and trauma patients
AU  - Marta Ulldemolins
AU  - Mohd Hafiz Abdul-Aziz
AU  - María Patricia Hernández-Mitre
AU  - Sazlyna Mohd Sazlly Lim
AU  - Andrew A. Udy
AU  - Manuel Colmenero
AU  - Peter Kruger
AU  - Carl M. J. Kirkpatrick
AU  - Michael S. Roberts
AU  - Steven C. Wallis
AU  - David L. Paterson
AU  - Jeffrey Lipman
AU  - Jason A. Roberts
PY  - 2026
DA  - 2026/08/06
JO  - Critical Care
DO  - 10.1186/s13054-026-06239-8
UR  - https://doi.org/10.1186/s13054-026-06239-8
AB  - 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.  Methods: 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.  Results: 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.  Conclusions: 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.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13054-026-06239-8.
SN  - 1364-8535
SN  - 1466-609X
ER  -