Fluoroquinolone Safety and Adverse Effects in Clinical Populations

Fluoroquinolones are a class of broad-spectrum antibiotics extensively employed in the treatment of respiratory, urinary and gastrointestinal infections. Despite their efficacy, accumulating evidence has revealed a pattern of serious adverse effects affecting musculoskeletal, connective tissue, neurological and metabolic systems. Spontaneous reports and observational studies have linked fluoroquinolones to tendinopathy, tendon rupture, peripheral neuropathy, aortic aneurysm and dissection, dysglycaemia, central nervous system disturbances and mitochondrial dysfunction. Underlying mechanisms include iron chelation leading to inhibition of α-ketoglutarate-dependent dioxygenases, disruption of extracellular matrix integrity via matrix metalloproteinase activation, mitochondrial membrane depolarisation and aberrant activation of mitogen-activated protein kinase pathways. Risk factors such as age over 60 years, concomitant corticosteroid therapy, renal impairment and pre-existing vascular or musculoskeletal disorders further amplify susceptibility. Regulatory bodies worldwide have issued warnings and restricted indications, prompting the development of newer fluoroquinolones with revised safety profiles. Clinical practice now emphasises judicious prescribing, patient education on early symptom recognition and vigilant post-marketing surveillance to balance therapeutic benefit against potential harm on a global scale.

Research from Nature Portfolio

Recent studies have quantified the association between fluoroquinolone exposure and collagen-related vascular events. A meta-analysis of observational cohorts and pharmacovigilance databases found that current use of fluoroquinolones doubled the odds of aortic dissection and aneurysm compared with non-use or use of other antibiotics. The odds ratio for dissection was approximately 2.38 and for aneurysm 1.98, with a combined risk increase for either event of 1.47. Based on baseline incidence rates, the number needed to harm for one additional major aortic event was estimated at around 7,246 patients treated for at least three days. These findings support a plausible causal link between fluoroquinolone therapy and accelerated collagen degradation in the aortic wall, reinforcing the need for mechanistic research and heightened clinical vigilance in at-risk populations.

Fluoroquinolone Safety and Adverse Effects in Clinical Populations publication trend

The graph below shows the total number of articles in fluoroquinolone safety and adverse effects in clinical populations across all publications each year (not limited to Nature Index journals).

Technical terms

Extracellular matrix (ECM): A network of proteins and polysaccharides that provides structural support to cells and tissues.

Mitogen-activated protein kinase (MAPK) pathways: Signalling cascades that regulate cell proliferation, differentiation and apoptosis.

Dioxygenases: Iron-dependent enzymes involved in hydroxylation reactions critical for epigenetic regulation and collagen maturation.

Tendinopathy: A spectrum of tendon disorders characterised by pain, swelling and impaired function, often culminating in rupture.

Number needed to harm (NNH): The estimated number of patients who must be treated for one to experience a specified adverse outcome.

References

1. Ciprofloxacin exacerbates dysfunction of smooth muscle cells in a microphysiological model of thoracic aortic aneurysm. JCI Insight (2023).
2. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells*. Journal of Biological Chemistry (2015).
3. Overview of Side-Effects of Antibacterial Fluoroquinolones: New Drugs versus Old Drugs, a Step Forward in the Safety Profile?. Pharmaceutics (2023).
4. Fluoroquinolone-associated suspected tendonitis and tendon rupture: A pharmacovigilance analysis from 2016 to 2021 based on the FAERS database. Frontiers in Pharmacology (2022).
5. Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea. BMC Ophthalmology (2003).
6. Quinolones-Induced Musculoskeletal, Neurological, and Psychiatric ADRs: A Pharmacovigilance Study Based on Data From the Italian Spontaneous Reporting System. Frontiers in Pharmacology (2020).
7. The association between fluoroquinolones and aortic dissection and aortic aneurysms: a systematic review and meta-analysis. Scientific Reports (2021).