Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
CMAJ. 2012 Oct 2;184(14):1565-70. doi: 10.1503/cmaj.111823. Epub 2012 Aug 13.
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, we examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents.
We conducted a population-based, nested, case-control study using health care data from Ontario for the period April 2002 to March 2011. We 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 broad-spectrum antibiotic agents: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil or clarithromycin. For each case, we 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. We calculated odds ratios (ORs) to determine the association between admission to hospital and previous exposure to an antibiotic agent, using clarithromycin as the reference.
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. We saw no such risk associated with the use of either ciprofloxacin or cefuroxime axetil.
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.
虽然氟喹诺酮类药物有时与氨基转移酶水平的轻度、短暂升高有关，但严重的急性肝损伤并不常见。监管警告已经确定莫西沙星具有肝毒性的特殊风险。因此，我们研究了使用莫西沙星与其他选定的抗生素药物相关的特发性急性肝损伤的风险。
我们使用安大略省 2002 年 4 月至 2011 年 3 月的医疗保健数据，进行了一项基于人群的、嵌套的病例对照研究。我们将病例定义为年龄在 66 岁或以上、无肝病史且在接受 5 种广谱抗生素处方后 30 天内因急性肝损伤住院的门诊患者：莫西沙星、左氧氟沙星、环丙沙星、头孢呋辛酯或克拉霉素。对于每个病例，我们从接受研究抗生素但未因急性肝损伤住院的患者中选择了最多 10 名年龄和性别匹配的对照。我们使用克拉霉素作为参考，计算了入院率和先前暴露于抗生素之间的比值比（OR），以确定关联。
共有 144 名患者在接受处方药物后 30 天内因急性肝损伤住院。其中 88 名（61.1%）患者在住院期间死亡。多变量调整后，使用莫西沙星（调整后的 OR 2.20，95%置信区间 [CI] 1.21-3.98）或左氧氟沙星（调整后的 OR 1.85，95% CI 1.01-3.39）与使用克拉霉素相比，急性肝损伤的风险增加。我们没有发现使用环丙沙星或头孢呋辛酯与这种风险相关。
在没有肝脏疾病证据的老年门诊患者中，莫西沙星和左氧氟沙星与克拉霉素相比，急性肝损伤的风险增加。
