Fluoroquinolone-Associated Myasthenia Gravis Exacerbation Evaluation of Postmarketing Reports from the US FDA Adverse Event Reporting System and a Literature Review
Fluoroquinolone-Associated Myasthenia Gravis Exacerbation Evaluation of Postmarketing Reports from the US FDA Adverse Event Reporting System and a Literature Review
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DOI：
10.2165/11593110-000000000-00000
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发表时间：
2011-01-01
期刊：
影响因子：
4.2
通讯作者：
Boucher, Robert M.
中科院分区：
文献类型：
--
作者：
Jones, S. Christopher;Sorbello, Alfred;Boucher, Robert M.
背景：在抗生素治疗的患者中有重症肌无力加重的报道。在实验诱导的重症肌无力的动物和体外模型中，氟喹诺酮类药物表现出神经肌肉阻断作用。目的：本回顾性研究的目的是评估提交给美国FDA的上市后不良事件报告和科学文献中发表的病例报告，以确定氟喹诺酮暴露与重症肌无力急性加重之间的潜在关联。方法：2011年3月1日，我们检索FDA不良事件报告系统（AERS）数据库，检索氟喹诺酮类药物治疗中重症肌无力加重作为严重不良事件的所有报告。我们还使用EMBASE对科学文献中的其他英语案例进行了基于互联网的搜索。结果：我们共发现了37例描述氟喹诺酮全身暴露后重症肌无力加重的独特病例。我们检索了27例使用氟喹诺酮类药物的非通气患者的AERS报告：左氧氟沙星（n=9）、莫西沙星（n=6）、环丙沙星（n=6）、氧氟沙星（n=2）、加替沙星（n=2）、诺氟沙星（n=1）和曲瓦沙星（n=1）。此外，我们检索了文献中发表的10例病例报告，涉及非通气患者服用环丙沙星（n=4）、左氧氟沙星（n=2）和氧氟沙星、诺氟沙星、培氟沙星和普卢利沙星（各1例）。氟喹诺酮暴露后重症肌无力加重的中位时间为1天。37例出现呼吸困难（n=19, 51%）、需要呼吸支持的肌无力危象（n=11, 30%）和死亡（n=2, 5%）。其他与加重相关的不良事件包括全身肌肉无力（n=20; 54%）、吞咽困难（n=9; 24%）、复视（n=6; 16%）和上睑下垂（n=6; 16%）。6例患者（16%）再次出现阳性反应，氟喹诺酮类药物重新引入后重症肌无力复发加重。结论：氟喹诺酮暴露可能导致有基础疾病的重症肌无力患者出现潜在的危及生命的加重。医疗保健专业人员应意识到这种严重的药物-疾病关联，并在治疗非通气性肌无力患者感染时仔细权衡氟喹诺酮类药物的利弊。
Background: Exacerbations of myasthenia gravis have been reported in antibacterial-treated patients. In animal and in vitro models of experimentally-induced myasthenia gravis, fluoroquinolones exhibit neuromuscular blockade.Objective: The aim of this retrospective study was to evaluate postmarketing adverse event reports submitted to the US FDA and case reports published in the scientific literature for a potential association between fluoroquinolone exposure and acute exacerbations of myasthenia gravis.Methods: On 1 March 2011, we searched the FDA Adverse Event Reporting System (AERS) database to retrieve all reports of myasthenia gravis exacerbation as a serious adverse event in patients treated with fluoroquinolones. We also conducted an Internet-based search using EMBASE for additional English-language cases in the scientific literature.Results: We identified a total of 37 unique cases describing myasthenia gravis exacerbation following fluoroquinolone systemic exposure. We retrieved AERS reports for 27 non-ventilated patients administered the following fluoroquinolones: levofloxacin (n=9), moxifloxacin (n=6), ciprofloxacin (n=6), ofloxacin (n=2), gatifloxacin (n=2), norfloxacin (n=1) and trovafloxacin (n=1). Additionally, we retrieved ten case reports published in the literature involving non-ventilated patients administered ciprofloxacin (n=4), levofloxacin (n=2) and ofloxacin, norfloxacin, pefloxacin and prulifloxacin (1 patient each). Myasthenia gravis exacerbations developed a median of 1 day following fluoroquinolone exposure. The 37 cases describe dyspnoea (n=19; 51%), myasthenic crisis requiring ventilatory support (n=11; 30%) and death (n=2; 5%). Additional exacerbation-related adverse events were generalized muscle weakness (n=20; 54%), dysphagia (n=9; 24%), diplopia (n=6; 16%) and ptosis (n=6; 16%). Six patients (16%) experienced a positive rechallenge, with recurrent myasthenia gravis exacerbation after fluoroquinolone reintroduction.Conclusions: Fluoroquinolone exposure may result in potentially life-threatening myasthenia gravis exacerbations in patients with underlying disease. Healthcare professionals should be aware of this serious drug-disease association and carefully weigh the benefit-risks of fluoroquinolones when treating infections in non-ventilated myasthenic patients.