title: Risk of acute liver injury associated with the use of moxifloxacin and other oral antimicrobials: a retrospective, population-based cohort study.
abstract: OBJECTIVE
  To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with nonusers of these antimicrobials.
  
  
  METHODS
  Retrospective, observational cohort study with a nested case-control analysis.
  
  
  METHODS
  HealthCore Integrated Research Database.
  
  
  METHODS
  Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use.
  
  
  RESULTS
  Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29-42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6-6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8-5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3-5.0), doxycycline (2.5, 95% CI 1.2-5.2), moxifloxacin (2.3, 95% CI 1.1-4.7), and amoxicillin (2.3, 95% CI 1.1-4.7).
  
  
  CONCLUSIONS
  The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.
authors.affiliation: Epidemiology, RTI Health Solutions, Waltham, Massachusetts.
authors.forename: James A
authors.initials: JA
authors.lastname: Kaye
authors.forename: Jordi
authors.initials: J
authors.lastname: Castellsague
authors.forename: Christine L
authors.initials: CL
authors.lastname: Bui
authors.forename: Brian
authors.initials: B
authors.lastname: Calingaert
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: McQuay
authors.forename: Nuria
authors.initials: N
authors.lastname: Riera-Guardia
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Saltus
authors.forename: Scott
authors.initials: S
authors.lastname: Quinlan
authors.forename: Crystal N
authors.initials: CN
authors.lastname: Holick
authors.forename: Peter M
authors.initials: PM
authors.lastname: Wahl
authors.forename: Kiliana
authors.initials: K
authors.lastname: Suzart
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rothman
authors.forename: Mari-Ann
authors.initials: MA
authors.lastname: Wallander
authors.forename: Susana
authors.initials: S
authors.lastname: Perez-Gutthann
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D012189:Retrospective Studies; D012306:Risk
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077266:Moxifloxacin
keywords: amoxicillin; antiinfective agents; drug-induced liver injury; epidemiology; fluoroquinolones; levofloxacin; moxifloxacin; telithromycin