title: Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin-Tazobactam or Cefepime.
abstract: Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in the AKI incidence between the TZP-VAN and FEP-VAN groups, evaluated using the risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria. Patients in the two groups were matched on the basis of age, sex, severity of illness, baseline creatinine clearance, hypotension, number of nephrotoxicity risk factors, and intravenous contrast exposure. In total, 4,193 patients met all inclusion criteria (3,605 received TZP-VAN and 588 received FEP-VAN). The unadjusted AKI incidence was 21.4% in patients receiving TZP-VAN, whereas it was 12.6% in patients receiving FEP-VAN (P < 0.001). After the patients were matched, 1,633 patients receiving TZP-VAN and 578 patients receiving FEP-VAN were evaluated. The AKI incidence remained higher in patients receiving TZP-VAN than in those receiving FEP-VAN (21.4% versus 12.5%, P < 0.0001). This trend remained true for all classifications of the RIFLE criteria. After controlling for remaining confounders, TZP-VAN therapy was associated with 2.18 times the odds of AKI than FEP-VAN therapy (95% confidence interval, 1.64 to 2.94 times) in logistic regression. AKI was significantly more common in patients receiving vancomycin in combination with piperacillin-tazobactam than in those receiving vancomycin in combination with cefepime. This finding reinforces the need for the judicious use of combination empirical antimicrobial therapy.
authors.affiliation: University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.|University of Kentucky HealthCare, Lexington, Kentucky, USA.
authors.forename: W Cliff
authors.initials: WC
authors.lastname: Rutter
authors.affiliation: University of Kentucky HealthCare, Lexington, Kentucky, USA.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Cox
authors.affiliation: University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.|University of Kentucky HealthCare, Lexington, Kentucky, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Martin
authors.affiliation: University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.|University of Kentucky HealthCare, Lexington, Kentucky, USA.
authors.forename: Donna R
authors.initials: DR
authors.lastname: Burgess
authors.affiliation: University of Kentucky College of Pharmacy, Lexington, Kentucky, USA david.burgess@uky.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Burgess
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D000077723:Cefepime; D002511:Cephalosporins / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010397:Penicillanic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010878:Piperacillin / Q000009:adverse effects / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D012189:Retrospective Studies; 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: adverse drug effects; beta-lactams; cefepime; nephrotoxicity; piperacillin-tazobactam; vancomycin