Ciprofloxacin not entirely safe-Has a dark side too

Use of fluoroquinolone group of antibiotic such as ciprofloxacin may be linked to the disruption of the normal functions of connective tissue, including tendon rupture, tendonitis, and retinal detachment, according to a study published in the journal JAMA Surgery.

"A natural tissue to worry about is the aorta, a blood vessel that relies heavily on having a sound connective tissue component - called the extracellular matrix - to maintain its integrity," said first author Dr. Scott A. LeMaire.

Previously two retrospective clinical studies were conducted to find out the association between fluoroquinolones and cardiovascular problems. The findings of the retrospective clinical studies showed an association between fluoroquinolone antibiotics and increased risk of aortic diseases but were not able to prove that the antibiotics cause the problems.

"They found that patients who received fluoroquinolones had a higher risk for aneurysms (formation of balloon-like areas in the aorta that weaken the integrity of the vessel), ruptures or dissections (tears in the wall) than patients who did not receive the antibiotics. This has raised important concerns," LeMaire said.

Scott A. LeMaire et al. conducted a study to examine the effect of ciprofloxacin on aortic aneurysm and dissection (AAD) development in mice.

The researchers provided the mice with normal or moderately stressed aortas with either ciprofloxacin or placebo and their aortas were examined after four weeks.

The study found that

• Normal, unstressed mice treated with ciprofloxacin did not show significant negative effects on the aorta.


• In mice with moderately stressed aortas that had received the placebo, 45 percent developed AAD, 24 percent developed aortic dissection and none had ruptured.


• 79 percent of the mice with moderately stressed aortas that received antibiotic developed AAD.


• 67 percent had an aortic dissection, and 15 percent had the fatal rupture. These results were similar in males and females.

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The investigators tried to find out the effects of ciprofloxacin on mouse aortas and the antibiotic's mechanism of action. A comparison was done between the aortas from stressed mice treated with the placebo and the aortic tissue of stressed mice treated with the antibiotic.

The authors found that aortic tissue of stressed mice treated with the antibiotic had a more destruction and fragmentation of elastic fibers; decreased activity of LOX, a key enzyme involved in stabilizing the extracellular matrix; increased activity of MMP enzymes involved in extracellular matrix degradation; and enhanced activation of cellular pathways that lead to cell death.

Separate laboratory experiments on human aortic smooth muscle cells revealed that sustained ciprofloxacin exposure reduced the expression of LOX while enhancing the expression of MMP and inducing cell death. In these experimental settings, the antibiotic is disrupting the natural processes that maintain the integrity of the extracellular matrix that is essential for normal aortic function.

The study concluded that the findings support the concerns raised by previous retrospective clinical studies and suggest that ciprofloxacin and other antibiotics of the same class should be used with caution in patients with aortic dilatation.

For reference log on to 10.1001/jamasurg.2018.1804