The US Food and Drug Administration (FDA) issued a black box warning for the class of antibiotics known as fluoroquinolones which includes the popularly prescribed Levaquin (levofloxacin), Avelox (moxifloxacin), and Cipro (ciprofloxacin).
The warning advises that the serious side effects associated with this class of antibiotics “generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated urinary tract infections who have other treatment options”. Instead fluoroquinolones should be reserved for the use of bacterial pneumonia, intra-abdominal infections, anthrax, and plague foremost.
The serious side effects can occur anywhere from hours to months after taking a fluoroquinolone and include peripheral neuropathy (permanent nerve damage), anxiety/depression, tendonitis, tendon rupture and exacerbation of myasthenia gravis (an autoimmune disease that affects skeletal muscle). In addition, recent studies link fluoroquinolones to collagen damage in the wall of the aorta (biggest artery in the body) that can lead to aneurysms (bulges) or dissection (tears) which can in turn lead to heart attacks, strokes, and death. And of course there are the side effects which I learnt in medical school in the early 2000s of QT prolongation and torsades de pointes.
Honestly, in medical school I got the impression that fluoroquinolones had an excellent safety record for adults. But these side effects are not brand new. Court documents have shown that manufacturers knew as early as 1996 that fluoroquinolones increased the risk of irreversible peripheral neuropathy but concealed the risks. The first FDA black box warning, the agency’s most serious warning, didn’t come until 2008. There remains several lawsuits against the manufacturers of fluoroquinolones including one against Johnson & Johnson in January this year.
This is a troubled history for the wonder drug class known as fluoroquinolones. Unlike many antimicrobials that were first isolated from living organisms, this class was synthesized by chemists in the lab. Nalidixic acid, a quinolone, was accidentally discovered in 1962 as a by-product during the synthesis of the antimalarial chloroquine. The term fluoroquinolone came later, when fluorine was added at the C-6 position of the molecule to create other drugs in the class.
In clinical practice, the use of fluoroquinolones has always generated discussion. Rampant prescribing, especially in the outpatient setting, has always been an issue and as an infectious disease physician one always questions if they are being used appropriately. Collateral damage includes the emergence of antimicrobial resistance (fluoroquinolone use has been linked to MRSA and VRE) and the increase of the potentially life-threatening C.difficile colitis, particularly the NAP1 strain.
Unfortunately, the claim of many patients that they have a penicillin allergy contributes to the overuse of fluoroquinolones. In addition many patients have allergies to sulfa or cannot take the sulfa-drug Bactrim (trimethoprim/sulfamethoxazole) as an alternative antibiotic because of kidney problems. In the geriatric population, using Macrobid/Macrodantin (nitrofurantoin) as an alternative antibiotic for uncomplicated urinary tract infection has generally been frowned upon but it might be the lesser of two evils.
In short, all antibiotics have risks, but fluoroquinolones are too risky for common uncomplicated and mild infections. Curbing the unnecessary use of fluoroquinolones will not only protect people from unnecessary suffering, but will also curb the rise of antimicrobial resistance and limit the incidence of C.difficile infections.
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