Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy
Association Between Peripheral Neuropathy and Exposure to Oral Fluoroquinolone or Amoxicillin-Clavulanate Therapy
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DOI：
10.1001/jamaneurol.2019.0887
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发表时间：
2019-07-01
期刊：
影响因子：
29
通讯作者：
Kurz, Xavier
中科院分区：
文献类型：
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作者：
Morales, Daniel;Pacurariu, Alexandra;Kurz, Xavier
重要性周围神经病变已与全身氟喹诺酮类药物暴露，但风险已经很难量化。目的计算相对和绝对风险估计的氟喹诺酮类药物暴露与周围神经病变的关联，并检查如何风险可能受到氟喹诺酮类药物暴露的时间和其他风险因素的影响。这项巢式病例对照研究使用了来自健康改善网络数据库（英国一个大型初级保健人口数据库）中常规登记的所有患者的匿名数据，从1月1日起，1999年至2015年12月31日。数据分析于2018年1月8日进行。该队列包括1338900名成年人发出1个或多个处方的氟喹诺酮类（34.3%）或阿莫西林-克拉维酸（65.7%）抗生素。通过使用从口服氟喹诺酮或阿莫西林-克拉维酸抗生素队列中选择的发病率密度抽样，将患有周围神经病变的成年人与最多4名对照组相匹配（年龄、性别、全科医生和日历时间）。计算氟喹诺酮类药物和阿莫西林-克拉维酸暴露的周围神经病变发生率比值，并与非糖尿病患者的非暴露进行比较，敏感性分析检验结果的一致性。然后估计人群平均校正率差异，包括不同氟喹诺酮治疗持续时间所需的伤害数量。暴露当前和累积暴露于口服氟喹诺酮或阿莫西林-克拉维酸类抗生素。主要结局和指标电子病历中记录的周围神经病变病例。2809名女性[52.4%]与17285名无糖尿病的对照组（9485名女性[54.9%]，平均[SD]年龄65.6 [14.7]岁）相匹配。当前口服氟喹诺酮暴露与周围神经病变的相对发生率增加相关（校正的发生率比，1.47; 95%CI，1.13-1.92）。当前氟喹诺酮暴露每增加一天，风险增加约3%，并在暴露后持续长达180天。口服阿莫西林-克拉维汀暴露未观察到风险显著增加。目前口服氟喹诺酮暴露的绝对风险为2.4（95%CI，1.8-3.1）/10000例患者/年。10天疗程所需的伤害人数为152083名患者（95%可信区间，117742-202778）结论和相关性本研究的结果表明口服氟喹诺酮类药物治疗与周围神经病变的发病风险增加有关，这可能取决于暴露的时间和治疗的时间。累积剂量卫生保健专业人员在处方氟喹诺酮类抗生素时应考虑这些潜在风险。
IMPORTANCE Peripheral neuropathy has been associated with systemic fluoroquinolone exposure, but risk has been poorly quantified.OBJECTIVE To calculate relative and absolute risk estimates for the association of fluoroquinolone exposure with peripheral neuropathy and to examine how risk may be affected by timing of fluoroquinolone exposure and by other risk factors.DESIGN, SETTING, AND PARTICIPANTS This nested case-control study used anonymized data from all patients routinely registered with general practices in The Health Improvement Network database, a large primary care population database in the United Kingdom, from January 1, 1999, to December 31, 2015. Data analyses were conducted January 8, 2018. The cohort consisted of 1338900 adults issued 1 or more prescriptions of fluoroquinolone (34.3%) or amoxicillin-clavulanate (65.7%) antibiotics. Adults with incident peripheral neuropathy were matched (on age, sex, general practice, and calendar time) with up to 4 controls by using incidence density sampling selected from a cohort prescribed oral fluoroquinolone or amoxicillin-clavulanate antibiotics. Incidence rate ratios of peripheral neuropathy were calculated for fluoroquinolone and for amoxicillin-clavulanate exposure and compared with nonexposure among patients without diabetes, with sensitivity analyses testing the consistency of the results. Population mean-adjusted rate differences were then estimated, including the number needed to harm for various durations of fluoroquinolone therapy.EXPOSURES Current and cumulative exposure to oral fluoroquinolone or amoxicillin-clavulanate antibiotics.MAIN OUTCOMES AND MEASURES Incident peripheral neuropathy cases recorded in electronic medical records.RESULTS In total, 5357 patients with incident peripheral neuropathy (mean [SD] age, 65.6 [14.7] years; 2809 women [52.4%]) were matched to 17285 controls (mean [SD] age, 64.4 [15.2] years; 9485 women [54.9%]) without diabetes. Current oral fluoroquinolone exposure was associated with an increased relative incidence of peripheral neuropathy compared with nonexposure (adjusted incident rate ratio, 1.47; 95% CI, 1.13-1.92). Risk increased by approximately 3% for each additional day of current fluoroquinolone exposure and persisted for up to 180 days following exposure. No significant increased risk was observed with oral amoxicillin-clavulanate exposure. The absolute risk with current oral fluoroquinolone exposure was 2.4 (95% CI, 1.8-3.1) per 10000 patients per year of current use. The number needed to harm for a 10-day course was 152083 patients (95% CI, 117742-202778) and was greatest among men and among patients older than 60 years.CONCLUSIONS AND RELEVANCE The results of the present study suggested that oral fluoroquinolone therapy was associated with an increased risk of incident peripheral neuropathy that may depend on the timing of the exposure and the cumulative dose. Health care professionals should consider these potential risks when prescribing fluoroquinolone antibiotics.