Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill.
Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill.
JAMA Surg. 2021 Mar 1;156(3):264-272. doi: 10.1001/jamasurg.2020.6165.
Although fluoroquinolones are commonly prescribed antibiotics in the US, recent international studies have shown an increased risk of aortic aneurysm and dissection after fluoroquinolone use, leading to US Food and Drug Administration warnings limiting use for high-risk patients. It is unclear whether these data are true for the US population and who is truly high risk.
To assess aortic aneurysm and dissection risks in a heterogeneous US population after fluoroquinolone use.
DESIGN, SETTING, AND PARTICIPANTS: Prescription fills for fluoroquinolones or a comparator antibiotic from 2005 to 2017 among commercially insured individuals aged 18 to 64 years were identified in this retrospective analysis of MarketScan health insurance claims. This cohort study included 27 827 254 US adults (47 596 545 antibiotic episodes), aged 18 to 64 years, with no known previous aortic aneurysm or dissection, no recent antibiotic exposure, and no recent hospitalization.
Outpatient fill of an oral fluoroquinolone or comparator antibiotic (amoxicillin-clavulanate, azithromycin, cephalexin, clindamycin, and sulfamethoxazole-trimethoprim).
The 90-day incidence of aortic aneurysm and dissection. Inverse probability of treatment weighting in Cox regression was used to estimate the association between fluoroquinolone fill and 90-day aneurysm incidence. Interaction terms were used to assess the association of known risk factors (ie, sex, age, and comorbidities) with aneurysm after fluoroquinolone use. Data analysis was performed March 2019 to May 2020.
Of 47 596 545 prescription fills, 9 053 961 (19%) were fluoroquinolones and 38 542 584 (81%) were comparator antibiotics. The median (interquartile range) age of adults with fluoroquinolone fills was 47 (36-57) years vs 43 (31-54) years with comparator antibiotic fills. Women comprised 61.3% of fluoroquinolone fills and 59.5% of comparator antibiotic fills. Before weighting, the 90-day incidence of newly diagnosed aneurysm was 7.5 cases per 10 000 fills (6752 of 9 053 961) after fluoroquinolones compared with 4.6 cases per 10 000 fills (17 627 of 38 542 584) after comparator antibiotics. After weighting for demographic characteristics and comorbidities, fluoroquinolone fills were associated with increased incidence of aneurysm formation (hazard ratio [HR], 1.20; 95% CI, 1.17-1.24). More specifically, compared with comparator antibiotics, fluoroquinolone fills were associated with increased 90-day incidence of abdominal aortic aneurysm (HR, 1.31; 95% CI, 1.25-1.37), iliac artery aneurysm (HR, 1.60; 95% CI, 1.33-1.91), and other abdominal aneurysm (HR, 1.58; 95% CI, 1.39-1.79), and adults were more likely to undergo aneurysm repair (HR, 1.88; 95% CI, 1.44-2.46). When stratified by age, all adults 35 years or older appeared at increased risk (18-34 years: HR, 0.99 [95% CI, 0.83-1.18]; 35-49 years: HR, 1.18 [95% CI, 1.09-1.28]; 50-64 years: HR, 1.24 [95% CI, 1.19-1.28]; P = .04).
This study found that fluoroquinolones were associated with increased incidence of aortic aneurysm formation in US adults. This association was consistent across adults aged 35 years or older, sex, and comorbidities, suggesting fluoroquinolone use should be pursued with caution in all adults, not just in high-risk individuals.
尽管氟喹诺酮类药物在美国是常用的抗生素，但最近的国际研究表明，氟喹诺酮类药物的使用与主动脉瘤和夹层的风险增加有关，这导致美国食品和药物管理局（FDA）发出警告，限制高危患者使用氟喹诺酮类药物。目前尚不清楚这些数据是否适用于美国人群，以及谁是真正的高危人群。
评估氟喹诺酮类药物在美国不同人群中的主动脉瘤和夹层风险。
设计、地点和参与者：这项回顾性市场扫描健康保险索赔分析研究中，鉴定了在 2005 年至 2017 年间，2782.7254 万名年龄在 18 至 64 岁之间的商业保险成年人的氟喹诺酮类药物或比较抗生素的处方剂量。该队列研究包括 2782.7254 万名年龄在 18 至 64 岁之间的美国成年人（4759.6545 次抗生素疗程），他们没有已知的先前的主动脉瘤或夹层，没有最近的抗生素暴露史，也没有最近的住院治疗史。
门诊氟喹诺酮类药物或比较抗生素（阿莫西林克拉维酸、阿奇霉素、头孢氨苄、克林霉素和磺胺甲噁唑-甲氧苄啶）的口服疗程。
90 天内主动脉瘤和夹层的发生率。Cox 回归的逆概率治疗加权用于估计氟喹诺酮类药物治疗与 90 天内动脉瘤发病率之间的关联。使用交互项评估已知风险因素（即性别、年龄和合并症）与氟喹诺酮类药物治疗后动脉瘤的关系。数据分析于 2019 年 3 月至 2020 年 5 月进行。
在 4759.6545 次处方剂量中，9053961 次（19%）为氟喹诺酮类药物，38542584 次（81%）为比较抗生素。氟喹诺酮类药物治疗组成年人的中位（四分位间距）年龄为 47（36-57）岁，而比较抗生素治疗组的年龄为 43（31-54）岁。女性占氟喹诺酮类药物治疗组的 61.3%，占比较抗生素治疗组的 59.5%。在加权之前，氟喹诺酮类药物治疗后新发动脉瘤的 90 天发生率为每 10000 次治疗 7.5 例（9053961 次治疗中的 6752 例），而比较抗生素治疗后为每 10000 次治疗 4.6 例（38542584 次治疗中的 17627 例）。在对人口统计学特征和合并症进行加权后，氟喹诺酮类药物治疗与动脉瘤形成发生率的增加相关（风险比[HR]，1.20；95%置信区间[CI]，1.17-1.24）。更具体地说，与比较抗生素相比，氟喹诺酮类药物治疗与 90 天内腹主动脉瘤（HR，1.31；95%CI，1.25-1.37）、髂动脉瘤（HR，1.60；95%CI，1.33-1.91）和其他腹部动脉瘤（HR，1.58；95%CI，1.39-1.79）的 90 天发生率增加有关，并且成年人更有可能接受动脉瘤修复（HR，1.88；95%CI，1.44-2.46）。按年龄分层时，所有 35 岁及以上的成年人似乎都面临更高的风险（18-34 岁：HR，0.99[95%CI，0.83-1.18]；35-49 岁：HR，1.18[95%CI，1.09-1.28]；50-64 岁：HR，1.24[95%CI，1.19-1.28]；P=0.04）。
本研究发现氟喹诺酮类药物与美国成年人主动脉瘤形成的发生率增加有关。这种关联在 35 岁或以上的成年人、性别和合并症中是一致的，这表明氟喹诺酮类药物的使用应谨慎，而不仅仅是在高危人群中。
