title: Drug-induced liver injury associated with high-dose ceftriaxone: a retrospective cohort study adjusted for the propensity score.
abstract: OBJECTIVE
  Ceftriaxone has been recognized as a well-tolerated drug; however, in some instances, liver dysfunction occurs after using high-dose ceftriaxone. We aimed to assess the incidence of liver injury due to high-dose ceftriaxone and to determine whether there is a dose-dependent risk of liver injury with this drug.
  
  
  METHODS
  We conducted a retrospective cohort study of hospitalized adult patients treated with ceftriaxone at a tertiary care hospital from January 2012 to October 2013. We collected demographic and clinical data by reviewing their medical records. The incidence of liver injury based on biochemical criteria, defined as a primary outcome, was compared between patients treated with high-dose ceftriaxone (4 g/day) and those treated with a normal dose of ceftriaxone (2 g/day) for ≥5 consecutive days. A propensity score for the use of high-dose ceftriaxone was calculated from five factors.
  
  
  RESULTS
  We identified 37 patients treated with high-dose ceftriaxone and 434 patients treated with a normal dose of ceftriaxone. Among these 471 patients, 15 patients (3.2 %) experienced liver injury, of whom six patients (6/37, 16.2 %) had received high-dose ceftriaxone and nine patients (9/434, 2.1 %) had received normal doses of ceftriaxone. In the multivariate analysis adjusted for the propensity score, high-dose ceftriaxone was independently associated with liver injury (odds ratio, 7.23; 95 % confidence interval, 2.01-26.0).
  
  
  CONCLUSIONS
  The present study revealed that high-dose ceftriaxone was associated with a significantly higher incidence of liver injury compared with the normal-dose regimen. Therefore, clinicians should carefully observe for signs of liver injury after high-dose ceftriaxone use.
authors.affiliation: Department of Infectious Diseases, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan. nakaharai@jikei.ac.jp.|Department of Infectious Diseases and Infection Control, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan. nakaharai@jikei.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakaharai
authors.affiliation: Department of Infectious Diseases, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Infectious Diseases, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan.|Department of Infection Control and Prevention, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yaita
authors.affiliation: Department of Infectious Diseases, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yoshimura
authors.affiliation: Department of Pharmacy, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan.|Department of Pharmacy, Yokohama Brain and Spine Center, 1-2-1 Takigashira, Isogo-ku, Yokohama, Kanagawa, 235-0012, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Igarashi
authors.affiliation: Department of Infectious Diseases, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-8555, Japan.
authors.forename: Natsuo
authors.initials: N
authors.lastname: Tachikawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002443:Ceftriaxone / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D012189:Retrospective Studies; D062606:Tertiary Care Centers / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone
keywords: Adverse drug reactions; Ceftriaxone; Drug-induced liver injury; Hepatotoxicity