Fluoroquinolones are a class of antibiotics approved to treat or prevent certain bacterial infections. Although they are used widely in India, it is observed through studies that they may lead to harmful side effects.

What are fluoroquinolones?

Quinolones are the largest rising class of antibacterial agents globally, to be used to treat pathogens in both hospitals and community settings. The most often used quinolones are ciprofloxacin, levofloxacin, and moxifloxacin etc. Prior clinical research on fluoroquinolones and aortic disease has been entirely focused on determining whether this class of antibiotics leads to the occurrence of aortic aneurysm and dissection in the overall patient group.

Two retrospective studies published in 2015 found a clear association between recent fluoroquinolone exposure and an elevated risk of aortic aneurysm, dissection, and rupture. While these results posed substantial questions, the studies included some significant shortcomings, prompting many—including the US Food and Drug Administration (FDA)—to request more data before recommending improvements in clinical practice. As a result, recent researchers have employed more refined methods to research design and interpretation in order to address a variety of shortcomings.

Fluoroquinolones are linked with an elevated 90-day prevalence of abdominal aortic aneurysms (HR, 1.31; 95 per cent confidence interval [CI], 1.25 to 1.37), iliac artery aneurysms (HR, 1.60; 95 per cent CI, 1.33 to 1.91), and other abdominal aneurysms (HR, 1.60; 95 per cent CI, 1.33 to 1.91). (HR, 1.58; 95 per cent CI, 1.39 to 1.79). Fluoroquinolone use was associated with a 31% increase in the occurrence of abdominal aortic aneurysms and a 61% increase in the incidence of iliac artery aneurysms.

In another recently published important study, Chen et al. identified 31,570 patients who got a new aortic aneurysm or aortic dissection diagnosis after a hospital admission using the Taiwan National Health Insurance Research Database. The investigators then examined the relationship between outpatient fluoroquinolone exposure and serious adverse events. They used a variety of analytic designs (including self-regulation and active comparator), a negative control exposure (amoxicillin), three negative control effects (fracture, trauma, and stroke), and sensitivity analyses to overcome significant possible shortcomings. Throughout their analyses, the investigators systematically reported that fluoroquinolone toxicity was associated with an elevated risk of all-cause mortality, aortic death, and both open and endovascular aortic surgery in patients with known aortic aneurysms or dissections.

Finally, it is concerning that 24% of patients with aortic disease in the cohort were treated as outpatients with fluoroquinolones at follow-up. This confirms the previous observation that 20% of patients with aortic aneurysms and dissections undergo fluoroquinolones during hospitalisation, highlighting the importance of potential attempts to reform prescription habits to include both inpatient and outpatient environments. There will be a need for research aimed at developing solutions for implementing emerging clinical practice guidelines, as well as evaluating and optimising their efficacy.

Warnings on the dangers of fluoroquinolones

The 2018 safety alert is one of many released by the FDA in recent years about fluoroquinolones. These antibiotics, which include ciprofloxacin, moxifloxacin, levofloxacin, gemifloxacin, and over 60 generics, have a wide range of activity against both gram-positive and gram-negative bacteria and are used to treat a host of mild bacterial infections.

In 2008, the agency posted a warning about the elevated risk of tendinitis and tendon rupture associated with fluoroquinolone use. This was accompanied by a 2013 label change warning that fluoroquinolones taken orally or by injection could result in peripheral neuropathy, a nerve disease characterised by fatigue, numbness, and pain in the hands and feet.

The FDA revised the black box warning in 2016, warning that fluoroquinolone use was linked to an increased risk of disabling and potentially permanent side effects including tendons, muscles, joints, nerves, and the central nervous system and that patients with acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections should avoid using them if other options are available.

In 2018, the Food and Drug Administration (FDA) updated its fluoroquinolone black box notices to say that patients with a history of aortic aneurysms, blockages of other blood arteries, or elevated blood pressure should consider alternate antibiotics. The FDA issued the alert after reviewing reports that showed fluoroquinolones were linked to an elevated risk of aortic aneurysm or dissection (a tear or separation in the lining of the aorta). In light of these findings, the existing US FDA black box recommendations are justified, but that they will need to be extended to cover younger adults with additional risk factors.

Fluoroquinolones use in India 

In India, fluoroquinolone antibiotics are widely used to treat a variety of bacterial infections. Fluoroquinolones account for 30 per cent of the global pharmaceutical market in India. In a nutshell, the Chen et al study adds significant data to the growing body of evidence indicating that fluoroquinolones can have an adverse impact on the aortic wall.

Additional laboratory and clinical trials are specifically needed to further our understanding of the risk and the optimal strategy for improving clinical practice. Meanwhile, considering the potentially fatal nature of the complications, it seems advisable to heed current FDA and European Medicines Agency warnings and avoid using these medications in patients at risk of aortic complications, especially those who already have aortic disease. For patients with or without aortic disease, it's time to reconsider the use of this class of antibiotics. More research is required to understand the mechanism of fluoroquinolone-induced aneurysm formation.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising super specialist from New Delhi.