title: Risk factors for kidney injury during vancomycin and piperacillin/tazobactam administration, including increased odds of injury with combination therapy.
abstract: BACKGROUND
  Acute kidney injury (AKI) occurs frequently in hospitalized patients and has been associated with the administration of certain medications. Concerns have been raised in recent reports that the antibiotic combination of vancomycin and piperacillin/tazobactam (combV/P) may be more associated with AKI than monotherapy with either drug.
  
  
  METHODS
  To compare the incidence of and risk factors for AKI in patients receiving combV/P versus monotherapy with either drug, a retrospective study was conducted in non-critically ill inpatients at a large urban teaching hospital. AKI was defined as either: (1) Increase in serum creatinine ≥0.5 mg/dl OR (2) ≥1.5-fold creatinine increase from admission baseline. In addition to standard multivariable regression adjustment, propensity score weighting was used as a robust approach to reduce the effects of covariate confounding when estimating the adjusted odds of AKI.
  
  
  RESULTS
  A total of 228 patients were evaluated. The overall incidence of AKI was 11.8 % (27 of 228 patients). AKI occurred in 4 of 101 patients in the vanc group (4.0 %), 4 of 26 patients in the piptazo group (15.4 %), and 19 of 101 patients in the combV/P group (18.8 %). The univariable odds of AKI was significantly lower in the vanc group compared to both the combV/P group (OR 0.178, 95 % CI 0.058-0.544, p = 0.003) and piptazo (OR 0.227, 95 % CI 0.053-0.978, p = 0.047) group. A multivariable model accounting for baseline characteristics again showed that vanc monotherapy was associated with lower odds of AKI than combV/P (OR 0.14, 95 % CI 0.04-0.52, p = 0.004). Male sex was also associated with lower odds of AKI (OR 0.28, 95 % CI 0.10-0.79, p = 0.02) in the multivariable model. In the propensity score analysis using inverse probability of treatment weighting (IPTW), vanc monotherapy and male sex were again associated with lower odds of AKI (OR 0.17; 95 % CI 0.04-0.62, p = 0.008 and OR 0.28, 95 % CI 0.09-0.89, p = 0.03, respectively).
  
  
  CONCLUSIONS
  This study substantiates recent reports that combV/P may be more associated with AKI than vanc monotherapy in hospital inpatients. AKI also appears to be more likely in females during therapy with these antimicrobials. While severity of illness is difficult to account for, these findings are further justification for narrowing antibiotic coverage when possible after this combination has been initiated in hospitalized patients.
authors.affiliation: Grady Health System Infectious Diseases Program, Atlanta, GA, USA. choetiffany@gmail.com.|Johns Hopkins Bayview Medical Center, Baltimore, MD, USA. choetiffany@gmail.com.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Kim
authors.affiliation: Grady Health System Infectious Diseases Program, Atlanta, GA, USA. sheetal.kandiah@emory.edu.|Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA, 30308, USA. sheetal.kandiah@emory.edu.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Kandiah
authors.affiliation: Grady Health System Infectious Diseases Program, Atlanta, GA, USA. mpatel1@gmh.edu.
authors.forename: Manish
authors.initials: M
authors.lastname: Patel
authors.affiliation: Grady Health System Infectious Diseases Program, Atlanta, GA, USA. srab@gmh.edu.
authors.forename: Saira
authors.initials: S
authors.lastname: Rab
authors.affiliation: Grady Health System Infectious Diseases Program, Atlanta, GA, USA. jwong@gradymemorial.onmicrosoft.com.
authors.forename: Jordan
authors.initials: J
authors.lastname: Wong
authors.affiliation: Biostatistics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. nora.xue@gmail.com.|Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA, USA. nora.xue@gmail.com.
authors.forename: Wenqiong
authors.initials: W
authors.lastname: Xue
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA, USA. keasle2@emory.edu.
authors.forename: Kirk
authors.initials: K
authors.lastname: Easley
authors.affiliation: Grady Health System Infectious Diseases Program, Atlanta, GA, USA. aande2@emory.edu.|Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA, 30308, USA. aande2@emory.edu.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Anderson
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010397:Penicillanic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D010878:Piperacillin / Q000009:adverse effects*; D012044:Regression Analysis; D012307:Risk Factors; D000078142:Tazobactam; D014640:Vancomycin / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin