Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study

Background — Although fluoroquinolones are sometimes associated with mild, transient elevations in aminotransferase levels, serious acute liver injury is uncommon. Regulatory warnings have identified moxifloxacin as presenting a particular risk of hepatotoxicity. Thus, the authors examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents.

Methods — The authors conducted a population-based, nested, case–control study using healthcare data from Ontario for the period April 2002 to March 2011. The authors identified cases as outpatients aged 66 years or older with no history of liver disease, and who were admitted to hospital for acute liver injury within 30 days of receiving a prescription for 1 of 5 broadspectrum antibiotic agents: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil or clarithromycin. For each case, the authors selected up to 10 age- and sex-matched controls from among patients who had received a study antibiotic, but who were not admitted to hospital for acute liver injury. The authors calculated odds ratios (ORs) to determine the association between admission to hospital and previous exposure to an antibiotic agent, using clarithromycin as the reference.

Results — A total of 144 patients were admitted to hospital for acute liver injury within 30 days of receiving a prescription for one of the identified drugs. Of these patients, 88 (61.1%) died while in hospital. After multivariable adjustment, use of either moxifloxacin (adjusted OR 2.20, 95% confidence interval [CI] 1.21–3.98) or levofloxacin (adjusted OR 1.85, 95% CI 1.01–3.39) was associated with an increase in risk of acute liver injury relative to the use of clarithromycin. The authors saw no such risk associated with the use of either ciprofloxacin or cefuroxime axetil.

Interpretation — Among older outpatients with no evidence of liver disease, moxifloxacin and levofloxacin were associated with an increased risk of acute liver injury relative to clarithromycin.