CMAJ：抗生素莫西沙星和左氧氟沙星或引发老年人肝脏损伤风险

近日，来自加拿大的研究人员表示，抗生素莫西沙星（moxifloxacin）和左氧氟沙星（levofloxacin）应当进行有效地监管控制，因为服用这两种抗生素对老年人有潜在的肝损伤风险。

相比使用抗生素克拉霉素，这些抗生素带来的肝损伤风险是前者的两倍。肝脏损伤包括中毒性肝病、肝炎、肝坏死或者未指明的急性肝衰竭。

“氟喹诺酮类抗生素是北美使用最广泛的一类抗生素，广谱福喹诺酮类抗生素的使用如左氧氟沙星和莫西沙星的用量正在逐年上升。”研究者David Junrlink表示。

然而，出于安全考虑，目前已经撤回了该类抗生素的其中几种，因为其存在严重的副作用，包括溶血、肝中毒等。研究小组对144位年龄为65岁以及65岁以上的病人进行调查研究（这些病人由于服用氟喹诺酮类抗生素，因肝中毒入院治疗），对照小组中只有10个病人（总数为1409）在服用抗生素之后没有副作用。

研究者表示，在患者服用抗生素和入院之间的时间间隔仅为9天，相比服用克拉霉素的病人来说，那些服用莫西沙星的病人在医院接受急性肝损伤治疗的比率是前者的2.2倍，而服用左氧氟沙星的病人则是服用克拉霉素病人的1.85倍。而服用环丙沙星和头孢呋辛酯所导致的肝损伤效果和服用克拉霉素并无明显差异。

克拉霉素被选为对比药物是因为其有氟喹诺酮类抗生素的典型临床特征，但其并不指示特异性的肝损伤，研究者的研究成果刊登在了近日的国际杂志Canadian Medical Association Journal上。

研究者表示，我们的研究成果为指导药物（抗生素）服用引发的肝脏损伤的相关治疗和避免措施提供了一定的基础和证据，但是我们的研究成果并没有揭示导致肝脏损伤的分子机制。

编译自：Common antibiotics may risk liver injury in elderly

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

Paterson JM, Mamdani MM, Manno M, Juurlink DN.

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, we examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents. METHODS: 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 broadspectrum 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. 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. We 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.