Wicherski Julia, Peltner Jonas, Becker Cornelia, Schüssel Katrin, Brückner Gabriela, Schlotmann Andreas, Schröder Helmut, Kern Winfried V, Haenisch Britta
Federal Institute for Drugs and Medical Devices (BfArM), Research Division, Pharmacoepidemiology, Bonn, Germany.
German Centre for Neurodegenerative Diseases (DZNE), Pharmacoepidemiology in Neurodegenerative Disorders, Bonn, Germany.
Pharmacotherapy. 2025 Jun;45(6):314-323. doi: 10.1002/phar.70020. Epub 2025 Apr 26.
To investigate the risk of aortic aneurysm or dissection associated with fluoroquinolone (FQ) prescription compared to macrolides in German routine health care data in order to replicate the recent study (Pharmacotherapy 2023;43:883) extending the results by contributing evidence for six additional broad-spectrum antibiotic classes as active comparators.
Cohort study in active comparator new user design comparing FQ with macrolides, tetracyclines, penicillins with extended spectrum, penicillins and beta-lactamase inhibitor combinations, second- and third-generation cephalosporins, sulfonamide and trimethoprim combinations, and lincosamides.
German statutory health insurance, the "Allgemeine Ortskrankenkasse" (AOK), January 2013 to December 2019.
Adults with at least one new prescription fill for FQ or active comparator antibiotics. New users were defined as individuals without antibiotic prescription fills, aortic aneurysm or dissection diagnoses, and hospitalization within 365 days prior to the cohort entry date. Users of FQ and active comparators were matched by nearest neighbor 1:1 propensity score matching.
Incident inpatient aortic aneurysm or dissection was observed within a 60-day risk window. In sensitivity analyses, an extended risk window of 90 days was applied, and specific FQ agents, dosages, and diagnoses were stratified.
FQ episodes were associated with an increased risk for aortic aneurysm or dissection compared to macrolides (aHR = 1.52 [1.33; 1.74]), which replicates the risk estimate of Garg et al. (aHR = 1.34 [1.17; 1.54]). This association was robust in a 90-day risk window and for ciprofloxacin, levofloxacin, and moxifloxacin. Moxifloxacin comprised the greatest risk of aortic aneurysm or dissection compared to macrolides (aHR = 2.13 [1.64; 2.77]). Moreover, we observed similar associations when comparing FQ to tetracyclines, penicillins with extended spectrum, cephalosporins, and lincosamides (aHR = 1.86 [1.54; 2.24], aHR = 1.45 [1.28; 1.65], aHR = 1.23 [1.10; 1.37], and aHR = 1.73 [1.43; 2.11]), respectively.
In a German cohort study, FQ use was associated with a 52% increased risk for aortic aneurysm or dissection within 60 days compared with macrolide use. The risk of FQ-associated aortic aneurysm or dissection compared to macrolides can be replicated in German routine health care data. Extending the analysis, we provided new insights that the effect size may depend on the chosen AC.
在德国常规医疗数据中，研究与大环内酯类药物相比，氟喹诺酮（FQ）处方相关的主动脉瘤或夹层的风险，以重复近期的研究（《药物治疗学》2023年；43卷：883页），通过为另外六种广谱抗生素类别作为活性对照提供证据来扩展研究结果。
采用活性对照新用户设计的队列研究，将FQ与大环内酯类、四环素类、广谱青霉素类、青霉素与β-内酰胺酶抑制剂组合、第二代和第三代头孢菌素类、磺胺类与甲氧苄啶组合以及林可酰胺类进行比较。
德国法定医疗保险，“Allgemeine Ortskrankenkasse”（AOK），2013年1月至2019年12月。
至少有一次新的FQ或活性对照抗生素处方配药的成年人。新用户定义为在队列入组日期前365天内无抗生素处方配药、主动脉瘤或夹层诊断以及住院治疗的个体。FQ和活性对照的使用者通过最近邻1:1倾向得分匹配进行匹配。
在60天的风险窗口内观察到的住院期间新发主动脉瘤或夹层。在敏感性分析中，采用90天的延长风险窗口，并对特定的FQ药物、剂量和诊断进行分层。
与大环内酯类相比，FQ用药与主动脉瘤或夹层风险增加相关（调整后风险比[aHR]=1.52[1.33；1.74]），这重复了加尔格等人的风险估计（aHR=1.34[1.17；1.54]）。这种关联在90天的风险窗口以及环丙沙星、左氧氟沙星和莫西沙星中都很稳健。与大环内酯类相比，莫西沙星导致主动脉瘤或夹层的风险最高（aHR=2.13[1.64；2.77]）。此外，当将FQ与四环素类、广谱青霉素类、头孢菌素类和林可酰胺类进行比较时，我们观察到了类似的关联（分别为aHR=1.86[1.54；2.24]、aHR=1.45[1.28；1.65]、aHR=1.23[
