Association of Fluoroquinolone Use With Short-term Risk of Development of Aortic Aneurysm

Abstract

IMPORTANCE 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. OBJECTIVE 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. EXPOSURES Outpatient fill of an oral fluoroquinolone or comparator antibiotic (amoxicillin-clavulanate, azithromycin, cephalexin, clindamycin, and sulfamethoxazoletrimethoprim). MAIN OUTCOMES AND MEASURESThe 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. RESULTSOf 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 (

Fluoroquinolones as a trigger for rupture of abdominal aortic aneurysm: A case‐crossover analysis

“…Dong et al conducted a nested case‐control study taking infections into account and found no association between FQ and a diagnosis of aortic aneurysm or dissection compared with other antibiotics and their corresponding indicated infections 27 . Lastly, Newton et al found in an observational study that the use of FQ was associated with an increased risk of a diagnosis of an aortic aneurysm compared with other antibiotics 28 …”

Fluoroquinolones-Associated Disability: It Is Not All in Your Head

“…Therefore, vagus nerve dysfunction may then have the opposite effect: an increased rate of aneurysm development and rupture. Interestingly, a recent cohort study reported an increased rate of aneurysms at the level of the aorta, which is innervated by a branch of the vagus nerve [136], after use of FQs compared with alternative antibiotics, especially in adults 35 years or older [137].…”

Fluoroquinolone-Induced Aortic Injury

“…Для пациентов 18-44 лет частота развития аневризмы и диссекции аорты при терапии ФХ минимальна, в период от 45 до 64 лет -увеличивается в 4 раза и достигает пика у пациентов в возрасте от 65 лет и старше [5]. Анализ результатов ретроспективного когортного исследования, проведенного в США [8], свидетельствует о том, что в группе повышенного риска развития аневризмы аорты находятся лица старше 35 лет: для пациентов в возрасте 18-34 года относительный риск составил 0,99 (95% доверительный интервал (ДИ) 0,83-1,18), 35-49 лет -1,18 (95% ДИ 1,09-1,28), 50-64 года -1,24 (95% ДИ 1,19-1,28) при уровне статистической значимости р = 0,04. По данным популяционного продольного когортного исследования, проведенного в Канаде [12], общий относительный риск развития аневризмы аорты при терапии ФХ у пациентов старше 65 лет составил 2,72 (95% ДИ 2,53-2,93).…”

“…Риск поражения аорты возрастает с увеличением дозы и длительности применения ФХ [18]. Как правило, поражение аорты на фоне приема ФХ развивалось в течение 60-90 сут с начала терапии [2,8,9,19]. Согласно данным C. C. Lee и соавт., терапия ФХ в течение 3-14 сут приводила к возрастанию риска развития аневризмы и диссекции аорты в 2,41 раза, а дольше 14 сут -в 2,83 раза [15].…”

“…Разрыв аневризмы аорты вызывает массивную кровопотерю и в 50-80% случаев приводит к летальному исходу [4]. Частота развития аневризмы и диссекции аорты на фоне терапии ФХ не превышает 0,3% [5][6][7], тем не менее риск их возникновения выше, чем при использовании других антибактериальных средств [8], что обусловливает необходимость детального изучения взаимосвязи между применением препаратов этой группы и развитием поражений аорты.…”