title: Use of doripenem and risk of seizure and renal impairment in US hospitalized patients: a retrospective cohort study.
abstract: OBJECTIVE
  A large retrospective database study was conducted to assess the incidence rate of treatment-emergent renal impairment/failure, seizure, and hemolytic anemia in doripenem and imipenem intravenous (IV)-exposed patients treated for complicated urinary tract infection (cUTI) and complicated intra-abdominal infection (cIAI) in US hospitals.
  
  
  METHODS
  Using the Premier Perspective™ Database (PPD), which maintains hospital discharge records for over 309 million patients, the incidence rate of treatment-emergent renal impairment/failure, seizure, and hemolytic anemia in the doripenem-treated compared with imipenem IV-treated population was examined.
  
  
  RESULTS
  The unadjusted doripenem rate ratio (RR) for renal impairment/failure relative to imipenem IV was 1.13 [95% confidence interval (CI) 1.07-1.21; p < 0.0001]. The unadjusted doripenem rate ratio for seizure relative to imipenem IV was 0.74 (95% CI 0.52-1.05; p = 0.07). In the comparative safety analysis, adjusted incidence rates of renal impairment/failure between doripenem-exposed patients and a propensity score-matched comparator cohort of imipenem IV-exposed patients showed no statistically significant difference in cUTI [RR = 1.02; 95% CI 0.93-1.12; p = 0.71] or cIAI (RR = 1.17; 95% CI 1.00-1.36; p = 0.05). Likewise, there was no statistically significant difference in adjusted incidence rates for seizures in doripenem-treated versus matched imipenem-treated patients for cUTI (RR = 0.69; 95% CI 0.41-1.14; p = 0.15) or cIAI (RR = 0.45; 95% CI 0.15-1.41; p = 0.17). No hemolytic anemia events were observed in this study.
  
  
  CONCLUSIONS
  In this large retrospective cohort study of US hospitalized patients, no statistically significant differences in the adjusted relative rates of renal impairment/failure and seizure were observed between doripenem and a propensity score-matched comparator cohort of imipenem IV patients in the treatment of cUTI and cIAI.
authors.affiliation: Janssen Research and Development, Titusville, NJ, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Chavers
authors.affiliation: Premier Inc., Charlotte, NC, USA.
authors.forename: Glenn
authors.initials: G
authors.lastname: Magee
authors.affiliation: Premier Inc., Charlotte, NC, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Baumer
authors.affiliation: Janssen Research and Development, 902 Route 202, 1124, Raritan, NJ 08869, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Pai
keywords: cIAI; cUTI; doripenem; imipenem; renal impairment; seizure