The dark side of common antibiotics

In a recent study, researchers found that the use of ciprofloxacin and other antibiotics of the class of fluoroquinolones is linked to disruption of the normal functions of connective tissue.

This could lead to tendon rupture, tendonitis, and retinal detachment.

Previous research findings have been reported in a number of journals.

They have resulted in the drugs currently having black box warning physicians and patients of the potential deleterious side effects.

Those research also suggests that other types of connective tissues might be involved.

Researchers conducted two retrospective clinical studies looked at the possible association between fluoroquinolones and cardiovascular 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.

Although the retrospective clinical studies point at an association between fluoroquinolone antibiotics and increased risk of aortic diseases, they do not prove that the antibiotics cause the problems.

To determine whether a cause-effect association exists, in the current study, researchers from Baylor College of Medicine worked with a mouse model of human aortic aneurysms and dissections (ADD).

Mice with normal or moderately stressed aortas received either ciprofloxacin or placebo and after four weeks we looked at their aortas.

The results showed 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% developed AAD, 24% developed aortic dissection and none had ruptured.

On the other hand, 79% of the mice with moderately stressed aortas that received antibiotic developed AAD, 67% had an aortic dissection, and 15% had a fatal rupture.

These results were similar in males and females.

The researchers then looked deeper into the effects of ciprofloxacin on mouse aortas searching for insights into the antibiotic’s mechanism of action.

Compared with the aortas from stressed mice treated with the placebo, the aortic tissue of stressed mice treated with the antibiotic showed more destruction and fragmentation of elastic fibers.

They also showed decreased activity of LOX, a key enzyme involved in stabilizing the extracellular matrix.

They also showed 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.

These 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.

The team believes they have enough evidence for changing guidelines on the use of fluoroquinolone antibiotics for people who have an aneurysm or are at risk of getting an aneurysm.

The first author Dr. Scott A. LeMaire is the director of research in the division of cardiothoracic surgery, vice-chair for research and professor of surgery and of molecular physiology and biophysics at Baylor College of Medicine.

The senior author Dr. Ying H. Shen, director of the Aortic Diseases Research Laboratory and associate professor of surgery at Baylor College of Medicine.

Read all the details of this study in JAMA Surgery.

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Source: JAMA Surgery.