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However, no clinical study has demonstrated synergistic toxicity, only that serum creatinine increases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>(i) Male Sprague\u2013Dawley rats (n\u2009=\u200932) received saline, vancomycin 150\u2009mg\/kg\/day intravenously, piperacillin\/tazobactam 1400\u2009mg\/kg\/day intraperitoneally or vancomycin + piperacillin\/tazobactam for 3\u2009days. Urinary biomarkers and histopathology were analysed. (ii) Cellular injury was assessed in NRK-52E cells using alamarBlue\u00ae.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Urinary output increased from Day \u22121 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\u2009&amp;lt;\u20090.001) and only on Day 3 with vancomycin + piperacillin\/tazobactam (P\u2009&amp;lt;\u20090.001, KIM-1; P\u2009&amp;lt;\u20090.05, clusterin). The histopathology injury score was elevated only in the vancomycin group when compared with piperacillin\/tazobactam as a control (P\u2009=\u20090.04) and generally not so with vancomycin + piperacillin\/tazobactam. In NRK-52E cells, vancomycin induced cell death with high doses (IC50 48.76\u2009mg\/mL) but piperacillin\/tazobactam did not, and vancomycin + piperacillin\/tazobactam was similar to vancomycin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkz563","type":"journal-article","created":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T07:05:39Z","timestamp":1576911939000},"page":"1228-1236","source":"Crossref","is-referenced-by-count":53,"title":["Lack of synergistic nephrotoxicity between vancomycin and piperacillin\/tazobactam in a rat model and a confirmatory cellular model"],"prefix":"10.1093","volume":"75","author":[{"given":"Gwendolyn M","family":"Pais","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA"},{"name":"Midwestern University, Chicago College of Pharmacy Pharmacometrics Center of Excellence, Downers Grove, IL, 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