dc.creator | Pais G.M., Liu J., Avedissian S.N., Hiner D., Xanthos T., Chalkias A., D'Aloja E., Locci E., Gilchrist A., Prozialeck W.C., Rhodes N.J., Lodise T.P., Fitzgerald J.C., Downes K.J., Zuppa A.F., Scheetz M.H. | en |
dc.date.accessioned | 2023-01-31T09:41:20Z | |
dc.date.available | 2023-01-31T09:41:20Z | |
dc.date.issued | 2020 | |
dc.identifier | 10.1093/jac/dkz563 | |
dc.identifier.issn | 03057453 | |
dc.identifier.uri | http://hdl.handle.net/11615/77428 | |
dc.description.abstract | Vancomycin 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. To 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®. Results: Urinary 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. Conclusions: All 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. © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. | en |
dc.language.iso | en | en |
dc.source | Journal of Antimicrobial Chemotherapy | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084024505&doi=10.1093%2fjac%2fdkz563&partnerID=40&md5=ef36615d4abcec3a1d8d219a3099ace3 | |
dc.subject | clusterin | en |
dc.subject | creatinine | en |
dc.subject | gentamicin | en |
dc.subject | kidney injury molecule 1 | en |
dc.subject | piperacillin plus tazobactam | en |
dc.subject | vancomycin | en |
dc.subject | biological marker | en |
dc.subject | cefepime | en |
dc.subject | gentamicin | en |
dc.subject | kim 1 protein | en |
dc.subject | piperacillin plus tazobactam | en |
dc.subject | unclassified drug | en |
dc.subject | vancomycin | en |
dc.subject | antiinfective agent | en |
dc.subject | penicillanic acid | en |
dc.subject | piperacillin | en |
dc.subject | vancomycin | en |
dc.subject | animal experiment | en |
dc.subject | animal model | en |
dc.subject | animal tissue | en |
dc.subject | Article | en |
dc.subject | cell damage | en |
dc.subject | cell viability | en |
dc.subject | controlled study | en |
dc.subject | creatinine blood level | en |
dc.subject | drug potentiation | en |
dc.subject | histopathology | en |
dc.subject | liquid chromatography-mass spectrometry | en |
dc.subject | male | en |
dc.subject | nephrotoxicity | en |
dc.subject | nonhuman | en |
dc.subject | NRK-52E cell line | en |
dc.subject | rat | en |
dc.subject | rat model | en |
dc.subject | renal protection | en |
dc.subject | urinalysis | en |
dc.subject | urine volume | en |
dc.subject | acute kidney failure | en |
dc.subject | adult | en |
dc.subject | animal cell | en |
dc.subject | blood sampling | en |
dc.subject | data analysis software | en |
dc.subject | death | en |
dc.subject | IC50 | en |
dc.subject | urine sampling | en |
dc.subject | animal | en |
dc.subject | combination drug therapy | en |
dc.subject | retrospective study | en |
dc.subject | Sprague Dawley rat | en |
dc.subject | toxicity | en |
dc.subject | Acute Kidney Injury | en |
dc.subject | Animals | en |
dc.subject | Anti-Bacterial Agents | en |
dc.subject | Drug Therapy, Combination | en |
dc.subject | Male | en |
dc.subject | Penicillanic Acid | en |
dc.subject | Piperacillin | en |
dc.subject | Piperacillin, Tazobactam Drug Combination | en |
dc.subject | Rats | en |
dc.subject | Rats, Sprague-Dawley | en |
dc.subject | Retrospective Studies | en |
dc.subject | Vancomycin | en |
dc.subject | Oxford University Press | en |
dc.title | Lack of synergistic nephrotoxicity between vancomycin and piperacillin/tazobactam in a rat model and a confirmatory cellular model | en |
dc.type | journalArticle | en |