title: A propensity-matched cohort study of vancomycin-associated nephrotoxicity in neonates.
abstract: BACKGROUND
  The incidence of nephrotoxicity among vancomycin-treated neonates has been reported to range from 2% to 20%. These widely varying estimates have led to confusion and controversy regarding the safety of vancomycin among neonates.
  
  
  OBJECTIVE
  Evaluate the incidence of nephrotoxicity among neonates receiving vancomycin concomitantly with gentamicin.
  
  
  METHODS
  Retrospective observational cohort study using propensity score matching to provide covariate balance between neonates who did or did not receive vancomycin based on factors known to be related to the development of renal dysfunction.
  
  
  METHODS
  Hospitals (n=22) throughout the Intermountain West, including a quaternary care children's hospital.
  
  
  METHODS
  Neonates ≤44 postmenstrual weeks (median gestational age: 31 (IQR 28-36) weeks) receiving intravenous gentamicin with or without exposure to vancomycin from January 2006 to December 2012.
  
  
  METHODS
  Nephrotoxicity based on the modified Acute Kidney Injury Network criteria for acute kidney injury (AKI) or serum creatinine concentration ≥1.5 mg/dL persisting for ≥48 h.
  
  
  RESULTS
  The final cohort was comprised of 1066 neonates (533 receiving vancomycin and gentamicin vs 533 receiving gentamicin). In a propensity score-matched cohort that was well balanced across 16 covariates, AKI was not associated with vancomycin use (16 neonates receiving vancomycin vs 7 controls experienced AKI; OR 1.5; 95% CI 0.6 to 4.0). However, the presence of a patent ductus arteriosus, concomitant non-steroidal anti-inflammatory drug use, ≥1 positive blood cultures, low birth weight and higher severity of illness and risk of mortality scores were associated with an increased risk of nephrotoxicity.
  
  
  CONCLUSIONS
  These results corroborate several earlier reports and much anecdotal evidence describing the infrequent occurrence of nephrotoxicity in neonates receiving concomitant vancomycin and gentamicin.
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Constance
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Balch
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Linakis
authors.affiliation: Pediatric Clinical Program, Intermountain Healthcare, Salt Lake City, Utah, USA.
authors.forename: E Kent
authors.initials: EK
authors.lastname: Korgenski
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Roberts
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Ward
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D016470:Bacteremia / Q000453:epidemiology; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D004374:Ductus Arteriosus, Patent / Q000453:epidemiology; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D057216:Propensity Score; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology; D014640:Vancomycin / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005839:Gentamicins; D014640:Vancomycin; D003404:Creatinine
keywords: gentamicin; neonate; nephrotoxicity; therapeutic drug monitoring; vancomycin