Fluoroquinolones make up one of the most prescribed classes of antibacterial medications. They have a wide antimicrobial spectrum of action and an excellent degree of oral bioavailability, which is why they are so widely used in treating infections. They are used to treat all sorts of infections, ranging from those that affect bone tissue to those that affect soft tissues in the lungs, digestive tract and genitourinary organs. It is well-known that antibacterial drugs must be prescribed rationally in order to prevent the occurrence of superinfections and antimicrobial resistance. However, medical practitioners should also always consider if a certain medication carries more risks than benefits before prescribing it to patients.
Unexpected side-effects of fluoroquinolones
The effect of fluoroquinolones on the dysregulation of the extracellular matrix was discovered in 2008. The United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) then issued a warning linking fluoroquinolones to tendon disorders, such as tendonitis and ruptures, due to this unexpected side-effect. Studies suggest that this side-effect’s underlying mechanism might be connected to the increase in the amount of matrix metalloproteinases (MMPs), which results in increased collagen degradation.
The effect of fluoroquinolones on the aorta
Just like tendons, the aorta is rich in collagen as well. The regulation of collagen production and degradation is essential for the normal functioning of the aorta – the largest blood vessel. The dysregulation of these two processes leads to aortic aneurysms and dissections. Given that fluoroquinolones directly affect the extracellular matrix, different studies have been conducted to investigate the link between fluoroquinolone usage and aortic disease.
A Canadian study from 2015  showed that tendon rupture occurred in 2,1% of patients above the age of 65 who took fluoroquinolones, whilst 1,1% of patients from the same experimental group developed an aortic aneurysm, a “new” symptom, in under 30 days since the beginning of treatment. Additional studies confirmed that patients who took fluoroquinolones had a 66% greater risk of developing an aortic dissection or aneurysm during a period of 60 days since the beginning of treatment than those who were prescribed penicillins.  This led to great concern and increased interest in the mechanism of these side-effects and the ways of dealing with them.
Aortopathy is an unpredictable and life-threatening medical condition. It is defined as a disorder of the aorta characterized by the abnormal remodelling of the aortic wall which ultimately leads to progressive weakening and dilatation of an aneurysm, aortic dissections or a catastrophic aortic rupture. Population studies estimate annual incidences to be as following: 2,4 – 14,8 cases per 100 000 people for aortic aneurysms and 3,8 – 8,8 cases per 100 000 people for aortic dissections. Despite their relative rarity in the overall population, aortic aneurysms and dissections are one of the most debilitating collagen-related medical conditions because they tend to have devastating outcomes. Known risk factors for the onset of aortopathy include congenital connective tissue disorders, hypertension, atherosclerosis, old age and smoking. Men are also more commonly affected than women.  
The underlying mechanism of aortopathy
Experiments have been conducted on an in vitro model of myofibroblasts isolated from the tissue of an aorta with an aneurysm. After treating them with clinically relevant doses of fluoroquinolones, scientists discovered that fluoroquinolone exposure reduces the expression of type I collagen depending on the exact dose. In addition to this, an imbalance is caused between MMPs and their tissue inhibitors (TIMPs), therefore facilitating the degradation of the extracellular matrix. 
It is also believed that fluoroquinolones are responsible for the reduction in the total amount of synthesised collagen due to their ability to form strong chelates with metal ions. Metal ions are important for the proper functioning of enzymes involved in post-translational modifications of collagen (e. g. prolyl-hydroxylase and lysyl-hydroxylase). These post-translational modifications are, in turn, important for the reticulation and structural rigidity of collagen fibres. 
Is there a solution?
Studies have shown that this side-effect is largely dose dependent and more frequent in older patients with pre-existing aortopathy. Therefore, guidelines state that fluoroquinolones should not be prescribed to such patients for uncomplicated infections where alternative drugs exist. If prescribing fluoroquinolones to an aortopathic patient is indispensable, they should be given out in smaller doses and with great caution.
What studies on fluoroquinolones taught us in the end
The first fluoroquinolones have been used medicinally since the 1980s. However, it took scientists more than 30 years to discover these “new” potentially life-threatening side-effects. That is precisely why monitoring and reporting new side-effects is important even after a drug becomes commercially available. Besides, it is an example of why continuous education is important in the biomedical field. The case of fluoroquinolone-induced aortopathy is indeed a serious one, serving as a reminder to all medical practitioners to follow the newest guidelines and discoveries while prescribing medication to patients.
2 Daneman N, Lu H, Redelmeier DA. Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study BMJ Open 2015, 5
3 Guzzardi DG et al. Induction of human aortic myofibroblast-mediated extracellular matrix dysregulation: A potential mechanism of fluoroquinolone-associated aortopathy. J Thorac Cardiovasc Surg. 2019, 157, 109-119
4 Pasternak B, Inghammar M, Svanström H. Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. BMJ. 2018, 360, 678
5 Wee I et al. The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis. Sci Rep. 2021, 11, 11073
6 Dong YH et al. Association of Infections and Use of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection. JAMA Intern Med. 2020, 180(12), 1587-1595
7 Zhang J, Zhang Z. Fluoroquinolones increase the risk of aortic aneurysm and dissection: A protocol for meta-analysis. Medicine (Baltimore). 2021, 100(51), e28081
8 Jun C, Fang B. Current progress of fluoroquinolones-increased risk of aortic aneurysm and dissection. BMC Cardiovasc Disord. 2021, 21(1), 470
2 Guzzardi DG et al. Induction of human aortic myofibroblast-mediated extracellular matrix dysregulation: A potential mechanism of fluoroquinolone-associated aortopathy. J Thorac Cardiovasc Surg. 2019, 157, 109-119