Fluoroquinolones Are Too Risky for Common Infections

An FDA panel says popular antibiotics such as Cipro are overprescribed and should have stronger warnings about dangerous side effects

By Teresa Carr / Consumer Reports / Last updated: March 07, 2016

Last November, Rachel Brummert, 45, of Charlotte, North Carolina, stood before a panel of experts and described the ever-worsening series of health problems, including 10 ruptured tendons and progressive nerve damage, she’s suffered as side effects of taking the antibiotic Levaquin, a type of fluoroquinolone, for a suspected sinus infection in 2006.

The Food and Drug Administration convened the panel to consider whether the official drug labels for fluoroquinolones, a group of antibiotics that includes drugs such as Cipro and Levaquin, should be changed to more clearly spell out their risks and discourage overuse. Brummert, the executive director of the Quinolone Vigilance Foundation, was one of more than 30 people who spoke during the open public hearing portion of the meeting about how the drugs had an impact on their lives.

“I am living proof that the risks in using a fluorquinolone to treat a routine infection far outweighs the benefits,” Brummert says.

After reviewing the evidence, the 21-member FDA panel agreed. They voted overwhelmingly that, in most cases, the benefit of fluoroquinolones to treat three common illnesses—bacterial sinus infections, urinary tract infections, and some forms of bronchitis in people with chronic lung disease—was outweighed by the risk of rare, but serious side effects, including irregular heartbeats, depression, nerve damage, ruptured tendons, and seizures.

Currently, those three illnesses account for nearly one-third of all fluoroquinolones prescribed outside of hospitals in the U.S. according to data presented by Janssen Pharmaceuticals, makers of Levaquin, at the FDA meeting.

While the fluroquinolones are essential for treating serious infections such as anthrax, the FDA panel members noted that they are overprescribed for common infections where other treatments would work just as well with less risk. They called on the FDA to strengthen labeled warnings and clarify when the drugs—should—and should not—be used.

Rampant Overprescribing

Over the last 30 years, the FDA has approved five fluroquinolone antibiotics to treat one or more of three illnesses considered by the panel: ciprofloxacin (Cipro), levofloxacin (Levaquin), moxifloxacin (Avelox), ofloxacin (Floxin), and gemifloxacin (Factive). All are also available as generics.

Much of the evidence on the risks of the drugs emerged after the drugs were on the market and used by millions of patients. While medical organizations such as the Infectious Diseases Society of America have updated their guidelines to advise against prescribing fluoroquinolones for milder garden-variety infections—including most cases of bronchitis, sinus infections, and urinary tract infections—many doctors haven’t gotten the message. That's likely because these powerful antibiotics work against a wide variety of bacteria, says Lindsey R. Baden, M.D., an infectious disease physician at Brigham and Women’s Hospital in Boston, Massachusetts, an associate professor at Harvard Medical School, and a member of the FDA panel. That can lead to overprescribing.

“Fluoroquinolones play an important role in treating serious infections such as those caused by bacteria that are resistant to other types of antibiotics,” says Baden. But in the case of less severe illnesses such as a mild bacterial sinus infection or uncomplicated bladder infection, the drugs “should typically be reserved for second-line or even third-line treatment after other antibiotics have failed,” says Baden.

When to Say 'No' to Cipro and Similar Drugs

Below we’ve listed three types of infections where fluoroquinolones are often not the best first choice for treatment along with our medical advisers’ advice about what to do instead.

• Sinus infections. “The vast majority of sinus infections are caused by a virus, not a bacteria and antibiotics don’t work against viruses,” says Baden. Even if bacteria are responsible, the infection will typically clear up on it’s own in a week or so. An antibiotic such as amoxicillin may be warranted if your symptoms last longer than a week, start to improve and then worsen, or are very severe—accompanied by a fever of 101.5 or higher, for example, or extreme pain and tenderness over your sinuses. For more information see Choosing Wisely recommendations from the American Academy of Allergy, Asthma, and Immunology. 
• Urinary tract infections (UTIs). If you have symptoms of a urinary tract infection such as having to urinate frequently, pain or burning when you go, cloudy or bloody urine, and a fever, you may need an antibiotic to treat the infection. Several types of antibiotics are effective against uncomplicated bladder infections; fluoroquinolones are typically only necessary if the infection is resistant to other antibiotics or has spread to the kidneys. Note that people aged 65 and older often have bacteria in their urine, but do not need to be tested or treated for a UTI unless they have symptoms. For more information see Choosing Wisely recommendations from the American Geriatric Society. 
• Bronchitis. As with sinus infections, most cases of bronchitis, or chest colds, are caused by a virus and are not helped by taking an antibiotic. (Read our advice on what to do ease symptoms while your body fights the infection.) One exception: patients with chronic obstructive pulmonary disease (COPD), a condition that causes difficulty breathing, may benefit from antibiotics if they develop symptoms severe enough to require hospitalization. In that case, the best choice of drug depends on the several factors, including which bacteria are prevalent in your area. For more information on using antibiotics to treat respiratory illness in children see Choosing Wisely recommendations from the American Academy of Pediatrics.

All Antibiotics Have Risk

Brummert says she hopes that the FDA will act on the advisory panel’s recommendations. “Curbing unnecessary prescribing of fluoroquinolones could save thousands of Americans from needless suffering,” she says.

Baden points out that all antibiotics—not just fluoroquinolones—should be used more thoughtfully.

“Really, I think the labels for all antibiotics should be strengthened to remind doctors and patients that when the drug is unwarranted, prescribing it has no benefit and exposes patients to needless risk, however small that risk may be,” says Baden. “Antibiotics are overused; as a community we need to be having these conversations about better prescribing based on the balance of benefits to harms.”

Editor's Note: This article and related materials are made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by the multistate settlement of consumer-fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).

A Brief History Of Antibiotic Resistance

The Grapevine

A Brief History Of Antibiotic Resistance: How A Medical Miracle Turned Into The Biggest Public Health Danger Of Our Time

Feb 17, 2016 09:30 AM By Lecia Bushak

The discovery of penicillin marked the advent of the age of antibiotics, 

an era where previously deadly infectious diseases could be cured in days. Wikimedia

Antibiotics, also known as antibacterials and antimicrobials, revolutionized medicine during the later half of the 20th century. But as time goes on, the success of antibiotics may be completely cancelled out by their combative counterparts: resistant bacteria.

Humans have overused antibiotics simply by harnessing them to treat all sorts of infections from pneumonia to strep throat — but also by sometimes taking too much of them, or infusing them into agricultural systems, animals, and food products, as the CDC illustrates . This overuse has opened the door for bacteria to evolve into resistant strains to beat out drugs. We’re now in a place where changes desperately need to be made in order to prevent millions of deaths from antibiotic resistance in the coming decades. These microscopic microbes seem to be smarter than us.

The authors of a 2010 report on the evolution of resistance note that microbes have “extraordinary genetic capabilities” that benefit “from man’s overuse of antibiotics to exploit every source of resistance genes... to develop [resistance] for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise.” Here’s how antibiotics went from being a revolutionizing medical breakthrough to a massive public health concern.

Which Came First, The Antibiotic Or The Resistance?

The antibiotic era, as it’s called, may not have begun until the 21st century, but antibiotics were still in use in ancient folk medicine. The term “antibiotic” has an extremely broad definition, describing the activity of any compound or chemical that can be applied to kill or inhibit bacteria that cause infectious diseases.

350-550 CE. The earliest traces of antibiotic use date back thousands of years. Tetracycline — a common antibiotic still used today — has been found in skeletons from Sudanese Nubia, an area that included ancient Egypt. Researchers believe that ancient Nubians were actually brewing tetracycline into their beers or otherwise incorporating it into their diets over a long period of time because the compound was found embedded deep in their bones and the population’s documented infectious diseases seem to be quite low. This discovery overturned the commonly-held belief that antibiotics didn’t exist before 1928.

It’s tough to detect other ancient antibiotics aside from tetracyclines, however, as most didn’t settle into bones and tooth enamel in the same way. Only documentation and anecdotes remain to give us insights into the use of other ancient antibiotics. What is now known to be an antimalarial drug, artemisinin, was used in ancient Chinese medicine, and it’s possible that herbalists also used moldy bread to prevent wounds from getting infected. There’s also historical evidence that, in Jordan, red soils rich in antibiotic-producing bacteria were used to treat skin infections like rashes.

And for as long as antibiotics have existed, bacterial resistance has existed alongside them — but never on such a large scale. “The natural history of antibiotic resistance genes can be revealed through the phylogenetic reconstruction,” the authors of one study write, “and this kind of analysis suggests the long-term presence of genes conferring resistance to several classes of antibiotics in nature well before the antibiotic era.” In short, bacteria have always been doing what they’re good at: finding ways to survive.

Alexander Fleming, who discovered penicillin, was also one of the first scientists
to warn about the perils of antibiotic resistance. Wikimedia

1928. Alexander Fleming, a Scottish biologist, took the fight against infections to a new level when he identified penicillin, making this the year that the modern antibiotic era began.

The discovery had apparently been an accident. Fleming had left an uncovered Petri dish of Staphylococcus bacteria near an open window in his basement lab, and in the morning found that mold growth had inhibited the bacteria. Penicillin, which comes from a type of fungi known as Penicillin rubens , became the first compound to be used officially as an antibiotic.

Penicillin was popular in the public during the 1940's and 50's due to its ability to treat a variety
of infectious diseases quickly; this also led to an increased build-up of antimicrobial resistance. Wikimedia

1943. Penicillin was on its way to mass production and was used heavily to treat Allied troops fighting in Europe during World War II. Considered a miracle drug, it was soon available to the public, despite warnings from Alexander Fleming that overuse could lead to mutant bacteria. Because bacteria can transfer genes horizontally — from one bacteria to another immediately — its ability to share resistance was adding to a growing threat unheeded by many scientists and doctors of the day.

1948. Transferring antibiotic use from medicine to agriculture also happened in a rather accidental way. Robert Stokstad, an animal nutritionist, and Thomas Jukes, a biochemist, were working at the company Lederle to develop an “animal protein factor” that could enhance chicken growth and boost poultry profits. The researchers were initially experimenting with vitamin B12, which was believed to boost animal growth, but eventually found that the cellular remains of Streptomyces aureofaciens bacteria — from which tetracyclines are extracted — contained a lot of the vitamin. As the Lederle labs had also discovered the first tetracycline, the researchers had access to plenty of these bacterial remains. Chicks that received supplements including Streptomyces auerofaciens grew 24 percent more than those receiving liver extract, which also contained high levels of B12. The bacteria shells, which still contained traces of the antibiotics, were more effective in making them grow (and much cheaper than liver extract). This discovery jump started the process of routinely injecting antibiotics into animals.

Meanwhile, resistant staph bacteria were growing in hospitals. According to Harvard Magazine, resistant staph infections in hospitals had risen from 14 percent in 1946 to 59 percent in 1948.

1952. By this time, doctors were somewhat aware of the possibility of antibiotic resistance, but overall they remained hopeful and optimistic about the success of these new drugs, which could defeat diseases that had long plagued humanity, like cholera and syphilis. A study on antibiotic resistance published that year concluded that syphilis could be treated “without any indications of an increased incidence of [resistant] infections, and this work gives grounds for hoping that the widespread use of penicillin will equally not result in an increasing incidence of infections resistant to penicillin.”

1950s–1970s. The next couple decades were considered the golden era of antibiotics, due to the sheer number of new drugs that were being developed: streptomycin, to treat serious infections like endocarditis and the plague; ampicillin, which treats respiratory tract infections and meningitis; and dozens of others. In the excitement surrounding the success of these antibiotics, they were made readily available to the public, like penicillin, ultimately paving the way for resistance to develop more easily.

The Tide Turns, The Superbugs Arrive

1955. As Fleming had predicted, resistance to penicillin gradually built up due to the accessibility of the drug. By 1955, many countries had attempted to slow this resistance by limiting penicillin use to prescription only, but it was too little too late: many bacterial strains had already defeated the antibiotic, including staphylococci.

1960. In an attempt to defeat penicillin-resistant strains, scientists developed methicillin, a different antibiotic in the penicillin class that could work against resistance. But within a year, bacterial strains developed resistance to methicillin too — eventually called MRSA , methicillin-resistant Staphylococcus aureus , or S. aureus . Now, MRSA can resist most antibiotics, and infections are common in hospitals — making it one of the biggest forerunners of multiple-drug resistant (MDR) bacteria.

For decades, poultry and other animal farms utilized antibiotics
freely in feed to promote growth. Reuters

1976. At Tufts University, a physician and researcher named Stuart Levy became one of the first to identify antibiotic resistance due to their use in animals, and to clamor for greater awareness of the problem. He worked on a study that year that examined how small amounts of antibiotics in animal feed could cause resistance in humans. On a farm in Massachusetts, Levy fed tetracycline to chickens, and found that tetracycline-resistant bacteria began to populate the chickens’ gut flora within a week. Despite this, rampant use of antibiotics like vancomycin (which had previously been considered a “last resort” drug) throughout the 1980’s led to an epidemic of resistant strains on farms and among humans.

1990s. A stronger resistant strain of MRSA began sickening normal, healthy people in the 1990s. This perhaps created a greater public awareness of the danger of antimicrobial resistance.

In the midst of emerging superbugs and MDR bacteria, the CDC and other
public health organizations began issuing public service announcements
to curb the liberal use of antibiotics. CDC / Wikimedia

By 2002 , up to 60 percent of S. aureus cases in hospitals were resistant to methicillin. In 2005, over 100,000 Americans were stricken with MRSA infections and some 20,000 died, more than the amount of people who were dying from HIV and tuberculosis combined, according to Harvard Magazine.

2012. As more researchers began working on the impending antibiotic-resistant epidemic, they had to tackle the classification of multidrug-resistant bacteria, which were multiplying by the minute. In a 2012 study, a team of scientists proposed adding the terms extensively drug-resistant (XDR) and pandrug-resistant (PDR) to multidrug-resistant (MDR) bacteria to better help them classify and potentially defeat these superbugs. It was the first time that researchers had a unified set of definitions for MDR bacteria to better understand them.

2013. After decades of certain researchers calling for action, the FDA finally implemented aplan to phase out certain antibiotic use in animals. But the extent to which this plan is effective at reducing the massive damage already done is difficult to identify.

2014. In response to major superbug outbreaks like Klebsiella pneumoniae (which causes pneumonia and bloodstream infections in the hospital) and gonorrhea strains all over the world, the World Health Organization (WHO) released a statement noting that “this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country.”

2015. McDonald's announced that it would phase out all meat sources that contained antibiotics, marking the first step of a major fast food company to heed the public health warnings and take action.

Since the 70s, very few new antimicrobial agents have been discovered, and the only way for researchers to combat resistant bacteria has been to modify already existing antibiotics. This has led to a standstill of sorts between current antibiotics and the rapidly adjusting “superbugs.”

Today, from farms to hospitals to everyday workplaces, animals and humans are likely teeming with different forms of resistant bacteria. In 2013, a Consumer Reports investigation showed that over half of ground turkey meat sold in the U.S. contained strains of drug-resistant bacteria. According to the CDC , some 2 million people in the U.S. are infected with drug-resistant bugs every year, and 23,000 of them die from these infections. Those numbers are likely to get worse in the coming decades, according to recent reports.

The danger of the situation is mainly in its complexity, Rustav Aminov writes in a 2010 report on antibiotic resistance: “It is not a single grand challenge; it is rather a complex problem requiring concerted efforts of microbiologists, ecologists, health care specialists, educationalists, policy makers, legislative bodies, agricultural and pharmaceutical industry workers, and the public to deal with. In fact, this should be of everyone's concern, because, in the end, there is always a probability for any of us at some stage to get infected with a pathogen that is resistant to antibiotic treatment.”

#SlamSuperbugs

Today Consumer Reports released the second magazine article in the three-part series on America's antibiotic crisis. This article, entitled How Your Hospital Can Make You Sick.It follows last month's article (The Rise of Superbugs), which was the first in our series. 

CR has been tweeting all day in English under the hashtag #SlamSuperbugs and in Spanish under the hashtag #AdiosSuperbacterias. Please join on Twitter and add your voice to the conversation. 

Please feel free to share these magazine articles widely with your family and friends as we all work together to curb the use of unneeded antibiotics. 

You can also go to the Consumer Reports e-hub on antibiotics to access patient-facing and Choosing Wisely-related materials on antibiotics.