ArticleThe Journal of antimicrobial chemotherapy2020
Lack of synergistic nephrotoxicity between vancomycin and piperacillin/tazobactam in a rat model and a confirmatory cellular model.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06954129 (Markers of Nephrotoxicity During Treatment With Antibiotic Combinations), which is not on this map. Cited by 39 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Markers of Nephrotoxicity During Treatment With Antibiotic Combinations: A Pragmatic Clinical Trial
Who cites it
39 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Risk factors for acute kidney injury in pediatric intensive care units: a systematic review and meta-analysis.BMC pediatrics · 2026Pooled it
- Association between concomitant use of vancomycin-piperacillin/tazobactam and acute kidney injury in real-world setting.Frontiers in physiology · 2026Pooled it
- Evaluating the risk of acute kidney injury and mortality associated with concomitant use of vancomycin with piperacillin/tazobactam or meropenem in critically ill and non-critically ill patients: a systematic review and meta-analysis.BMC infectious diseases · 2025Pooled it
- Risk Stratification for Vancomycin-Associated Acute Kidney Injury in Chinese Adult Inpatients: A Multicenter Retrospective Cohort Study.Infection and drug resistance · 2026Article
- Transition From Intraoperative Vancomycin-Piperacillin Tazobactam to Vancomycin-Cefepime Does Not Change Acute Kidney Injury or Renal Recovery Outcomes in Patients Undergoing Heart Transplantation.Clinical transplantation · 2025Article
- Protamine protects against vancomycin-induced kidney injury.Antimicrobial agents and chemotherapy · 2025Article
- Practice preference and evidence analysis on topical use of tobramycin powder in lumbar spine surgery: A Multi-National AO spine survey with systematic review of the literature.World neurosurgery: X · 2024Review
- Effect modification of dosing strategy (AUC or trough) on AKI associated with vancomycin in combination with piperacillin/tazobactam or cefepime and meropenem.Antimicrobial agents and chemotherapy · 2024Article
- Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.British journal of pharmacology · 2024Article
- Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy.JAC-antimicrobial resistance · 2024Article
- Nut Cracked? Does the ACORN Trial End the Debate Surrounding Vancomycin and Piperacillin-Tazobactam Combination Therapy and Increased Risk for Acute Kidney Injury?Open forum infectious diseases · 2024Article
- Incidence of Antimicrobial-Associated Acute Kidney Injury in Children: A Structured Review.Paediatric drugs · 2024Review
- Overview of Antibiotic-Induced Nephrotoxicity.Kidney international reports · 2023Review
- Article
- Iohexol-Measured Glomerular Filtration Rate and Urinary Biomarker Changes between Vancomycin and Vancomycin Plus Piperacillin-Tazobactam in a Translational Rat Model.Antimicrobial agents and chemotherapy · 2023Article
- Article
- Mechanisms of Piperacillin/Tazobactam Nephrotoxicity: Piperacillin/Tazobactam-Induced Direct Tubular Damage in Mice.Antibiotics (Basel, Switzerland) · 2023Article
- Iohexol-measured glomerular filtration rate and urinary biomarker changes between vancomycin and vancomycin plus piperacillin-tazobactam in a translational rat model.bioRxiv : the preprint server for biology · 2023Article
- Impact of Vancomycin Loading Doses and Dose Escalation on Glomerular Function and Kidney Injury Biomarkers in a Translational Rat Model.Antimicrobial agents and chemotherapy · 2023Article
- Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury.The Journal of antimicrobial chemotherapy · 2023Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundVancomycin and piperacillin/tazobactam are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated synergistic toxicity, only that serum creatinine increases.
objectivesTo clarify the potential for synergistic toxicity between vancomycin, piperacillin/tazobactam and vancomycin + piperacillin/tazobactam treatments by quantifying kidney injury in a translational rat model of AKI and using cell studies.
methods(i) Male Sprague-Dawley rats (n = 32) received saline, vancomycin 150 mg/kg/day intravenously, piperacillin/tazobactam 1400 mg/kg/day intraperitoneally or vancomycin + piperacillin/tazobactam for 3 days. Urinary biomarkers and histopathology were analysed. (ii) Cellular injury was assessed in NRK-52E cells using alamarBlue®.
resultsUrinary output increased from Day -1 to Day 1 with vancomycin but only after Day 2 for vancomycin + piperacillin/tazobactam-treated rats. Plasma creatinine was elevated from baseline with vancomycin by Day 2 and only by Day 4 for vancomycin + piperacillin/tazobactam. Urinary KIM-1 and clusterin were increased with vancomycin from Day 1 versus controls (P < 0.001) and only on Day 3 with vancomycin + piperacillin/tazobactam (P < 0.001, KIM-1; P < 0.05, clusterin). The histopathology injury score was elevated only in the vancomycin group when compared with piperacillin/tazobactam as a control (P = 0.04) and generally not so with vancomycin + piperacillin/tazobactam. In NRK-52E cells, vancomycin induced cell death with high doses (IC50 48.76 mg/mL) but piperacillin/tazobactam did not, and vancomycin + piperacillin/tazobactam was similar to vancomycin.
conclusionsAll groups treated with vancomycin demonstrated AKI; however, vancomycin + piperacillin/tazobactam was not worse than vancomycin. Histopathology suggested that piperacillin/tazobactam did not worsen vancomycin-induced AKI and may even be protective.
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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.