title: Acute Kidney Injury in Patients Treated with IV Beta-Lactam/Beta-Lactamase Inhibitor Combinations.
abstract: OBJECTIVE
  Increased acute kidney injury (AKI) incidence has been reported in patients receiving piperacillin-tazobactam (PTZ) therapy compared with other β-lactams. The authors sought to determine if the addition of β-lactamase inhibitors impacts AKI incidence by comparing patients treated with PTZ or ampicillin-sulbactam (SAM).
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Large academic tertiary care hospital.
  
  
  METHODS
  Overall, 2448 patients received PTZ (n=1836) or SAM (n=612) for at least 48 hours between September 1, 2007, and September 30, 2015. Patients were excluded for pregnancy, cystic fibrosis, chronic kidney disease, and initial creatinine clearance < 30 ml/min. Patients were matched on Charlson Comorbidity Index, initial creatinine clearance, hypotension exposure, various nephrotoxic drug exposures, history of diabetes, heart failure, and hypertension.
  
  
  RESULTS
  AKI occurred in 265 patients at similar rates for both groups (PTZ 11.4% vs SAM 9.2%; p=0.14). After stratifying by vancomycin exposure and controlling for confounders, there was no difference in the risk of AKI for SAM or PTZ (adjusted odds ratio [aOR] 0.87, 95% confidence interval [CI] 0.59-1.25). The addition of vancomycin (VAN) to PTZ increased the likelihood of AKI compared with PTZ alone (aOR 1.77, 95% CI 1.26-2.46). Concomitant SAM and VAN therapy was not associated with a significant increase in AKI compared with SAM monotherapy (aOR 1.01, 95% CI 0.48-1.97).
  
  
  CONCLUSIONS
  Rates of AKI were similar for PTZ and SAM in a matched cohort. The addition of a β-lactamase inhibitor is not likely the mechanism in the observed increased rates of AKI in patients treated with vancomycin and PTZ.
authors.affiliation: University of Kentucky College of Pharmacy, Lexington, Kentucky.|University of Kentucky HealthCare, Lexington, Kentucky.
authors.forename: W Cliff
authors.initials: WC
authors.lastname: Rutter
authors.affiliation: University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors.forename: David S
authors.initials: DS
authors.lastname: Burgess
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000008:administration & dosage / Q000009:adverse effects; D000077725:Piperacillin, Tazobactam Drug Combination; D012189:Retrospective Studies; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects*; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D047090:beta-Lactams / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D014640:Vancomycin; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: acute kidney injury; ampicillin-sulbactam; beta-lactam/beta-lactamase inhibitor combinations; piperacillin-tazobactam; vancomycin