The basic chemical structure of fluoroquinolone antibiotics such as Avelox, Cipro and Levaquin.... [+]
I've been following fluoroquinolone antibiotics ever since I was a graduate student in the 1980s. We were working on a class of enzymes shared by bacteria and higher organisms called topoisomerases. One of the bacterial forms of this enzyme (called DNA gyrase) is the target of quinolone and fluoroquinolone antibiotics.
Nalidixic acid was the first of these quinolone antibiotics, invented in the 1960s by researchers studying the antimalarial drug, chloroquine. The best known fluoroquinolone is ciprofloxacin (Cipro), first introduced in 1987. These antibiotics revolutionized the treatment of infections by stubborn, gram-negative bacteria. The World Health Organization includes ciprofloxacin on its list of essential medicines, those that meet the basic minimum for a healthcare system.
I first learned of the unexpected side effects of fluoroquinolones early in my faculty career when I read Stephen Fried's book, Bitter Pills: Inside the Hazardous World of Legal Drugs. Fried's wife, Diane, suffered an infrequent side effect of mental confusion and delirium from ofloxacin (Floxin), samples of which were inappropriately given to her by gynecologist for a urinary tract infection.
While central nervous system problems can occur with fluroquinolones, an equally puzzling side effect on the major tendons of the body can also occur in some people. I distinctly recall a pharmacist friend walking into our daycare center with immobilization boots on both feet because a fluoroquinolone antibiotic had caused her Achilles tendons to rupture. These antibiotics can sometimes cause collagen degradation in tendons, but no one can explain why this only occurs in a small percentage of patients. But the FDA has been warning about this side effect since 2008.
(And so have Forbes contributors. While reading more about this topic, I came across a nice 2012 piece on fluoroquinolone side effects by former FORBES contributor Melanie Haiken where she received 70 comments and almost 150,000 views.)
Fluoroquinolones already contain black-box warnings for these side effects as well as other warnings about potentially irreversible peripheral neuropathy and potential worsening of myasthenia gravis, an autoimmune disorder that causes muscle weakness and fatigue.
But fluoroquinolones are essential last-resort antibiotics for severe infections. That's why most of them are still on the market: Avelox (moxifloxacin), Cipro (ciprofloxacin), Factive (gemifloxacin), Levaquin (levofloxacin) and generic ofloxacin.
This past week, the FDA announced it is updating the labels of fluoroquinolones and warning doctors not to use fluoroquinolones in cases of acute bacterial sinusitis, bacterial exacerbation of chronic bronchitis, or uncomplicated urinary tract infections where drugs of other classes have not been tried first. I'm honestly surprised that this warning is still required because all doctors I know are very judicious about the use of these antibiotics. But, alas, not all doctors.
The FDA is also notifying patients given a fluoroquinolone to alert their doctor at the first sign of any unusual joint or tendon pain, muscle weakness, tingling or "pins and needles" sensations, numbness in the arms or legs, confusion or hallucinations.
The stimulus for this latest announcement is that FDA's continued pharmacovigilance efforts have identified that two or more of these rare side effects can sometimes occur together in some patients. While they issued a warning to this effect in May 2016, drug labeling was not updated at the time.
Still, fluoroquinolones are essential drugs, especially in complicated infections with gram-negative bacteria. But their liabilities illustrate yet another reason why we still need to develop new antibiotics.
