title: Risk of Acute Kidney Injury in Patients on Concomitant Vancomycin and Piperacillin-Tazobactam Compared to Those on Vancomycin and Cefepime.
abstract: BACKGROUND
  Recent evidence suggests that among patients receiving vancomycin, receipt of concomitant piperacillin-tazobactam increases the risk of nephrotoxicity. Well-controlled, adequately powered studies comparing rates of acute kidney injury (AKI) among patients receiving vancomycin + piperacillin-tazobactam (VPT) compared to similar patients receiving vancomycin + cefepime (VC) are lacking. In this study we compared the incidence of AKI among patients receiving combination therapy with VPT to a matched group receiving VC.
  
  
  METHODS
  A retrospective, matched, cohort study was performed. Patients were eligible if they received combination therapy for ≥48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dL or they were receiving renal replacement therapy. Patients receiving VC were matched to patients receiving VPT based on severity of illness, intensive care unit status, duration of combination therapy, vancomycin dose, and number of concomitant nephrotoxins. The primary outcome was the incidence of AKI. Multivariate modeling was performed using Cox proportional hazards.
  
  
  RESULTS
  A total of 558 patients were included. AKI rates were significantly higher in the VPT group than the VC group (81/279 [29%] vs 31/279 [11%]). In multivariate analysis, therapy with VPT was an independent predictor for AKI (hazard ratio = 4.27; 95% confidence interval, 2.73-6.68). Among patients who developed AKI, the median onset was more rapid in the VPT group compared to the VC group (3 vs 5 days P =< .0001).
  
  
  CONCLUSIONS
  The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination.
authors.affiliation: Department of Medicine, Detroit Medical Center, and.|Wayne State University School of Medicine, Detroit.
authors.forename: Bhagyashri
authors.initials: B
authors.lastname: Navalkele
authors.affiliation: Wayne State University School of Medicine, Detroit; jpogue@dmc.org.|Department of Pharmacy Services, Sinai-Grace Hospital, Detroit, Michigan.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Pogue
authors.affiliation: Department of Medicine, Detroit Medical Center, and.|Wayne State University School of Medicine, Detroit.
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Karino
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Bakht
authors.initials: B
authors.lastname: Nishan
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Madiha
authors.initials: M
authors.lastname: Salim
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Solanki
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Amina
authors.initials: A
authors.lastname: Pervaiz
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Nader
authors.initials: N
authors.lastname: Tashtoush
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Hamadullah
authors.initials: H
authors.lastname: Shaikh
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Sunitha
authors.initials: S
authors.lastname: Koppula
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Koons
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: Tanveer
authors.initials: T
authors.lastname: Hussain
authors.affiliation: Wayne State University School of Medicine, Detroit.
authors.forename: William
authors.initials: W
authors.lastname: Perry
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.
authors.forename: Richard
authors.initials: R
authors.lastname: Evans
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor.
authors.forename: Emily T
authors.initials: ET
authors.lastname: Martin
authors.affiliation: Department of Pharmacy Services, Detroit Receiving Hospital.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Mynatt
authors.affiliation: Department of Pharmacy Services, Huron Valley Sinai Hospital.
authors.forename: Kyle P
authors.initials: KP
authors.lastname: Murray
authors.affiliation: Wayne State University School of Medicine, Detroit.|Department of Pharmacy Services, Detroit Receiving Hospital.|Anti-Infective Research Laboratory, Department of Pharmacy Practice, Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
authors.affiliation: Department of Medicine, Detroit Medical Center, and.|Wayne State University School of Medicine, Detroit.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology* / Q000628:therapy; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000077723:Cefepime; D002511:Cephalosporins / Q000009:adverse effects* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010397:Penicillanic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000009:adverse effects; D000077725:Piperacillin, Tazobactam Drug Combination; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D012720:Severity of Illness Index; D014640:Vancomycin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000077725:Piperacillin, Tazobactam Drug Combination; D014640:Vancomycin; D000077723:Cefepime; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: acute kidney injury; cefepime; nephrotoxicity.; piperacillin–tazobactam; vancomycin