{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:18:22Z","timestamp":1789075102626,"version":"build-2803163510"},"reference-count":22,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Nephrotoxicity caused by use of vancomycin and piperacillin\u2013tazobactam has been heavily debated, and specific impact of this combination on development of acute kidney injury (AKI) has remained uncertain. We sought to further elucidate the risk factors contributing to nephrotoxicity. Methods: We conducted a retrospective cohort study at our academic medical center from May 2019 to March 2023. We included adult patients who received at least 48 h of dual vancomycin and piperacillin\u2013tazobactam therapy. The primary outcome is incidence of kidney injury along with determinants of AKI. Patients were stratified into two groups according to occurrence of AKI or its absence. Demographic features, concomitant use of nephrotoxic agents, site of infection, use of vasopressors, duration of therapy, and vancomycin-level parameters were compared. Results: Of 350 patients, AKI occurred in 89 patients (25.4%). The 30-day mortality was comparable between the two groups. No significant differences were observed in age, gender, race, or comorbidities, although more AKI cases occurred in African American patients (51.7%). Elevated initial vancomycin trough and estimated area under the curve\/minimum inhibitory concentration levels, higher mean body mass index (BMI), and use of intravenous (IV) contrast were more frequently observed in the AKI group. Conclusions: We demonstrated that 25.4% of patients receiving vancomycin and piperacillin\u2013tazobactam combination experienced AKI, while higher BMI and use of concomitant IV contrast were significantly associated with increased nephrotoxicity. Therefore, we suggest proceeding with caution regarding use of vancomycin and piperacillin\u2013tazobactam in patients with elevated BMI and those who have received IV contrast.<\/jats:p>","DOI":"10.3390\/jcm15135020","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T08:45:20Z","timestamp":1782722720000},"page":"5020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Factors Affecting Vancomycin and Piperacillin\u2013Tazobactam-Induced Nephrotoxicity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3109-7784","authenticated-orcid":false,"given":"Mollie VanNatta","family":"Day","sequence":"first","affiliation":[{"name":"Ochsner LSU Health Shreveport, Academic Medical Center, 1541 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhul","family":"Munshi","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, School of Medicine, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyn","family":"Picard","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, School of Medicine, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7867-4502","authenticated-orcid":false,"given":"Alexandre E.","family":"Malek","sequence":"additional","affiliation":[{"name":"Ochsner LSU Health Shreveport, Academic Medical Center, 1541 Kings Highway, Shreveport, LA 71103, USA"},{"name":"Division of Infectious Disease, Department of Medicine, School of Medicine, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.2146\/ajhp080434","article-title":"Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists","volume":"66","author":"Rybak","year":"2009","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1128\/AAC.01568-12","article-title":"Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter","volume":"57","author":"Paterson","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/ajhp\/zxaa036","article-title":"Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists","volume":"77","author":"Rybak","year":"2020","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.clinthera.2007.06.014","article-title":"A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia","volume":"29","author":"Jeffres","year":"2007","journal-title":"Clin. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5475","DOI":"10.1128\/AAC.00168-11","article-title":"Relationship between Vancomycin Trough Concentrations and Nephrotoxicity: A Prospective Multicenter Trial","volume":"55","author":"Bosso","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.2215\/CJN.05920616","article-title":"Vancomycin and the risk of AKI: A systematic review and metaanalysis","volume":"11","author":"Haikal","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/cid\/ciw709","article-title":"Risk of Acute Kidney Injury in Patients on Concomitant Vancomycin and Piperacillin\u2013Tazobactam Compared to Those on Vancomycin and Cefepime","volume":"64","author":"Navalkele","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/jac\/dkae410","article-title":"Vancomycin combined with piperacillin\/tazobactam increases the risk of acute kidney injury compared with vancomycin plus other anti-pseudomonal beta-lactams: A systematic review and network meta-analysis","volume":"80","author":"Pan","year":"2025","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.tox.2005.07.009","article-title":"In vivo evidences suggesting the role of oxidative stress in pathogenesis of vancomycin-induced nephrotoxicity: Protection by erdosteine","volume":"215","author":"Oktem","year":"2005","journal-title":"Toxicology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1001\/archinte.165.7.790","article-title":"Concealed Renal Insufficiency and Adverse Drug Reactions in Elderly Hospitalized Patients","volume":"165","author":"Corsonello","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/phar.1428","article-title":"Comparison of Acute Kidney Injury During Treatment with Vancomycin in Combination with Piperacillin-Tazobactam or Cefepime","volume":"34","author":"Gomes","year":"2014","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_12","first-page":"743","article-title":"Drug-induced nephrotoxicity","volume":"78","author":"Naughton","year":"2008","journal-title":"Am. Fam. Physician"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kan, W.-C., Chen, Y.-C., Wu, V.-C., and Shiao, C.-C. (2022). Vancomycin-Associated Acute Kidney Injury: A Narrative Review from Pathophysiology to Clinical Application. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042052"},{"key":"ref_14","unstructured":"(2023, May 01). Vancomycin Calculator. Vancomycin Calculator-ClinCalc.com. Available online: https:\/\/clincalc.com\/vancomycin\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"R204","DOI":"10.1186\/cc2872","article-title":"Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group","volume":"8","author":"Bellomo","year":"2004","journal-title":"Crit. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1186\/cc5713","article-title":"Acute Kidney Injury Network. Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury","volume":"11","author":"Mehta","year":"2007","journal-title":"Crit. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"dlad157","DOI":"10.1093\/jacamr\/dlad157","article-title":"Association of piperacillin and vancomycin exposure on acute kidney injury during combination therapy","volume":"6","author":"Venugopalan","year":"2024","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"ofac491","DOI":"10.1093\/ofid\/ofac491","article-title":"Evaluation of Vancomycin Accumulation in Patients With Obesity","volume":"9","author":"Assadoon","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1086\/600884","article-title":"Relationship between Initial Vancomycin Concentration-Time Profile and Nephrotoxicity among Hospitalized Patients","volume":"40","author":"Lodise","year":"2009","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"ofaf205","DOI":"10.1093\/ofid\/ofaf205","article-title":"Rates of Acute Kidney Injury Utilizing Area Under the Concentration\u2013Time Curve Versus Trough-Based Vancomycin Dosing Strategies in Patients With Obesity","volume":"12","author":"Guidry","year":"2025","journal-title":"Open Forum Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jin, J., Xu, J., Xu, S., Hu, J., Jiang, W., Shen, B., Wang, C., Teng, J., and Ding, X. (2021). Hemodilution is associated with underestimation of serum creatinine in cardiac surgery patients: A retrospective analysis. BMC Cardiovasc. Disord., 21.","DOI":"10.1186\/s12872-021-01879-w"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/5020\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T09:50:53Z","timestamp":1782726653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/5020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,27]]},"references-count":22,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15135020"],"URL":"https:\/\/doi.org\/10.3390\/jcm15135020","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,27]]}}}